Application of radiation technology in vaccines development
Identifieur interne : 000506 ( Pmc/Corpus ); précédent : 000505; suivant : 000507Application of radiation technology in vaccines development
Auteurs : Ho Seong SeoSource :
- Clinical and Experimental Vaccine Research [ 2287-3651 ] ; 2015.
Abstract
One of the earliest methods used in the manufacture of stable and safe vaccines is the use of chemical and physical treatments to produce inactivated forms of pathogens. Although these types of vaccines have been successful in eliciting specific humoral immune responses to pathogen-associated immunogens, there is a large demand for the development of fast, safe, and effective vaccine manufacturing strategies. Radiation sterilization has been used to develop a variety of vaccine types, because it can eradicate chemical contaminants and penetrate pathogens to destroy nucleic acids without damaging the pathogen surface antigens. Nevertheless, irradiated vaccines have not widely been used at an industrial level because of difficulties obtaining the necessary equipment. Recent successful clinical trials of irradiated vaccines against pathogens and tumors have led to a reevaluation of radiation technology as an alternative method to produce vaccines. In the present article, we review the challenges associated with creating irradiated vaccines and discuss potential strategies for developing vaccines using radiation technology.
Url:
DOI: 10.7774/cevr.2015.4.2.145
PubMed: 26273573
PubMed Central: 4524899
Links to Exploration step
PMC:4524899Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Application of radiation technology in vaccines development</title>
<author><name sortKey="Seo, Ho Seong" sort="Seo, Ho Seong" uniqKey="Seo H" first="Ho Seong" last="Seo">Ho Seong Seo</name>
<affiliation><nlm:aff id="A1">Radiation Biotechnology Research Division, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Korea.</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">26273573</idno>
<idno type="pmc">4524899</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524899</idno>
<idno type="RBID">PMC:4524899</idno>
<idno type="doi">10.7774/cevr.2015.4.2.145</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000506</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000506</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Application of radiation technology in vaccines development</title>
<author><name sortKey="Seo, Ho Seong" sort="Seo, Ho Seong" uniqKey="Seo H" first="Ho Seong" last="Seo">Ho Seong Seo</name>
<affiliation><nlm:aff id="A1">Radiation Biotechnology Research Division, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Korea.</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Clinical and Experimental Vaccine Research</title>
<idno type="ISSN">2287-3651</idno>
<idno type="eISSN">2287-366X</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>One of the earliest methods used in the manufacture of stable and safe vaccines is the use of chemical and physical treatments to produce inactivated forms of pathogens. Although these types of vaccines have been successful in eliciting specific humoral immune responses to pathogen-associated immunogens, there is a large demand for the development of fast, safe, and effective vaccine manufacturing strategies. Radiation sterilization has been used to develop a variety of vaccine types, because it can eradicate chemical contaminants and penetrate pathogens to destroy nucleic acids without damaging the pathogen surface antigens. Nevertheless, irradiated vaccines have not widely been used at an industrial level because of difficulties obtaining the necessary equipment. Recent successful clinical trials of irradiated vaccines against pathogens and tumors have led to a reevaluation of radiation technology as an alternative method to produce vaccines. In the present article, we review the challenges associated with creating irradiated vaccines and discuss potential strategies for developing vaccines using radiation technology.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Delaney, Tf" uniqKey="Delaney T">TF DeLaney</name>
</author>
<author><name sortKey="Trofimov, Av" uniqKey="Trofimov A">AV Trofimov</name>
</author>
<author><name sortKey="Engelsman, M" uniqKey="Engelsman M">M Engelsman</name>
</author>
<author><name sortKey="Suit, Hd" uniqKey="Suit H">HD Suit</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Barker, Ca" uniqKey="Barker C">CA Barker</name>
</author>
<author><name sortKey="Postow, Ma" uniqKey="Postow M">MA Postow</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Amin, Np" uniqKey="Amin N">NP Amin</name>
</author>
<author><name sortKey="Sher, Dj" uniqKey="Sher D">DJ Sher</name>
</author>
<author><name sortKey="Konski, Aa" uniqKey="Konski A">AA Konski</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mcdonald, Jc" uniqKey="Mcdonald J">JC McDonald</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Musilek, L" uniqKey="Musilek L">L Musilek</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Awan, Ms" uniqKey="Awan M">MS Awan</name>
</author>
<author><name sortKey="Tabbasam, N" uniqKey="Tabbasam N">N Tabbasam</name>
</author>
<author><name sortKey="Ayub, N" uniqKey="Ayub N">N Ayub</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Galante, Am" uniqKey="Galante A">AM Galante</name>
</author>
<author><name sortKey="Campos, Ll" uniqKey="Campos L">LL Campos</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Choi, Ji" uniqKey="Choi J">JI Choi</name>
</author>
<author><name sortKey="Yoon, M" uniqKey="Yoon M">M Yoon</name>
</author>
<author><name sortKey="Joe, M" uniqKey="Joe M">M Joe</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sugimoto, T" uniqKey="Sugimoto T">T Sugimoto</name>
</author>
<author><name sortKey="Shinozaki, T" uniqKey="Shinozaki T">T Shinozaki</name>
</author>
<author><name sortKey="Naruse, T" uniqKey="Naruse T">T Naruse</name>
</author>
<author><name sortKey="Miyamoto, Y" uniqKey="Miyamoto Y">Y Miyamoto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cho, Hw" uniqKey="Cho H">HW Cho</name>
</author>
<author><name sortKey="Howard, Cr" uniqKey="Howard C">CR Howard</name>
</author>
<author><name sortKey="Lee, Hw" uniqKey="Lee H">HW Lee</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mckeage, K" uniqKey="Mckeage K">K McKeage</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Grassly, Nc" uniqKey="Grassly N">NC Grassly</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gasparini, R" uniqKey="Gasparini R">R Gasparini</name>
</author>
<author><name sortKey="Amicizia, D" uniqKey="Amicizia D">D Amicizia</name>
</author>
<author><name sortKey="Lai, Pl" uniqKey="Lai P">PL Lai</name>
</author>
<author><name sortKey="Panatto, D" uniqKey="Panatto D">D Panatto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mayr, A" uniqKey="Mayr A">A Mayr</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thomas, Tn" uniqKey="Thomas T">TN Thomas</name>
</author>
<author><name sortKey="Reef, S" uniqKey="Reef S">S Reef</name>
</author>
<author><name sortKey="Neff, L" uniqKey="Neff L">L Neff</name>
</author>
<author><name sortKey="Sniadack, Mm" uniqKey="Sniadack M">MM Sniadack</name>
</author>
<author><name sortKey="Mootrey, Gt" uniqKey="Mootrey G">GT Mootrey</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Brown, Cc" uniqKey="Brown C">CC Brown</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Njeumi, F" uniqKey="Njeumi F">F Njeumi</name>
</author>
<author><name sortKey="Taylor, W" uniqKey="Taylor W">W Taylor</name>
</author>
<author><name sortKey="Diallo, A" uniqKey="Diallo A">A Diallo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Luke, Tc" uniqKey="Luke T">TC Luke</name>
</author>
<author><name sortKey="Hoffman, Sl" uniqKey="Hoffman S">SL Hoffman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hewitson, Jp" uniqKey="Hewitson J">JP Hewitson</name>
</author>
<author><name sortKey="Hamblin, Pa" uniqKey="Hamblin P">PA Hamblin</name>
</author>
<author><name sortKey="Mountford, Ap" uniqKey="Mountford A">AP Mountford</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Plotkin, Sa" uniqKey="Plotkin S">SA Plotkin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Artenstein, Aw" uniqKey="Artenstein A">AW Artenstein</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Arama, C" uniqKey="Arama C">C Arama</name>
</author>
<author><name sortKey="Troye Blomberg, M" uniqKey="Troye Blomberg M">M Troye-Blomberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jindal, H" uniqKey="Jindal H">H Jindal</name>
</author>
<author><name sortKey="Bhatt, B" uniqKey="Bhatt B">B Bhatt</name>
</author>
<author><name sortKey="Malik, Js" uniqKey="Malik J">JS Malik</name>
</author>
<author><name sortKey="Sk, S" uniqKey="Sk S">S Sk</name>
</author>
<author><name sortKey="Mehta, B" uniqKey="Mehta B">B Mehta</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Qin, L" uniqKey="Qin L">L Qin</name>
</author>
<author><name sortKey="Smith, Bd" uniqKey="Smith B">BD Smith</name>
</author>
<author><name sortKey="Tsai, Hl" uniqKey="Tsai H">HL Tsai</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="De Remigis, A" uniqKey="De Remigis A">A De Remigis</name>
</author>
<author><name sortKey="De Gruijl, Td" uniqKey="De Gruijl T">TD de Gruijl</name>
</author>
<author><name sortKey="Uram, Jn" uniqKey="Uram J">JN Uram</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Le, Dt" uniqKey="Le D">DT Le</name>
</author>
<author><name sortKey="Wang Gillam, A" uniqKey="Wang Gillam A">A Wang-Gillam</name>
</author>
<author><name sortKey="Picozzi, V" uniqKey="Picozzi V">V Picozzi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rappuoli, R" uniqKey="Rappuoli R">R Rappuoli</name>
</author>
<author><name sortKey="Bagnoli, F" uniqKey="Bagnoli F">F Bagnoli</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Plotkin, Sa" uniqKey="Plotkin S">SA Plotkin</name>
</author>
<author><name sortKey="Orenstein, Wa" uniqKey="Orenstein W">WA Orenstein</name>
</author>
<author><name sortKey="Offit, Pa" uniqKey="Offit P">PA Offit</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Madsen, T" uniqKey="Madsen T">T Madsen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Brown, F" uniqKey="Brown F">F Brown</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Perrin, P" uniqKey="Perrin P">P Perrin</name>
</author>
<author><name sortKey="Morgeaux, S" uniqKey="Morgeaux S">S Morgeaux</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Uittenbogaard, Jp" uniqKey="Uittenbogaard J">JP Uittenbogaard</name>
</author>
<author><name sortKey="Zomer, B" uniqKey="Zomer B">B Zomer</name>
</author>
<author><name sortKey="Hoogerhout, P" uniqKey="Hoogerhout P">P Hoogerhout</name>
</author>
<author><name sortKey="Metz, B" uniqKey="Metz B">B Metz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Swanson, Mc" uniqKey="Swanson M">MC Swanson</name>
</author>
<author><name sortKey="Rosanoff, E" uniqKey="Rosanoff E">E Rosanoff</name>
</author>
<author><name sortKey="Gurwith, M" uniqKey="Gurwith M">M Gurwith</name>
</author>
<author><name sortKey="Deitch, M" uniqKey="Deitch M">M Deitch</name>
</author>
<author><name sortKey="Schnurrenberger, P" uniqKey="Schnurrenberger P">P Schnurrenberger</name>
</author>
<author><name sortKey="Reed, Ce" uniqKey="Reed C">CE Reed</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stauffer, Ao" uniqKey="Stauffer A">AO Stauffer</name>
</author>
<author><name sortKey="Barbosa, Vc" uniqKey="Barbosa V">VC Barbosa</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Horl, Wh" uniqKey="Horl W">WH Horl</name>
</author>
<author><name sortKey="Riegel, W" uniqKey="Riegel W">W Riegel</name>
</author>
<author><name sortKey="Schollmeyer, P" uniqKey="Schollmeyer P">P Schollmeyer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dean, Ee" uniqKey="Dean E">EE Dean</name>
</author>
<author><name sortKey="Howie, Dl" uniqKey="Howie D">DL Howie</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Goldblith, Sa" uniqKey="Goldblith S">SA Goldblith</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Datta, M" uniqKey="Datta M">M Datta</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Datta, Sk" uniqKey="Datta S">SK Datta</name>
</author>
<author><name sortKey="Okamoto, S" uniqKey="Okamoto S">S Okamoto</name>
</author>
<author><name sortKey="Hayashi, T" uniqKey="Hayashi T">T Hayashi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Magnani, Dm" uniqKey="Magnani D">DM Magnani</name>
</author>
<author><name sortKey="Harms, Js" uniqKey="Harms J">JS Harms</name>
</author>
<author><name sortKey="Durward, Ma" uniqKey="Durward M">MA Durward</name>
</author>
<author><name sortKey="Splitter, Ga" uniqKey="Splitter G">GA Splitter</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Quach, C" uniqKey="Quach C">C Quach</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wutzler, P" uniqKey="Wutzler P">P Wutzler</name>
</author>
<author><name sortKey="Hardt, R" uniqKey="Hardt R">R Hardt</name>
</author>
<author><name sortKey="Knuf, M" uniqKey="Knuf M">M Knuf</name>
</author>
<author><name sortKey="Wahle, K" uniqKey="Wahle K">K Wahle</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pica, N" uniqKey="Pica N">N Pica</name>
</author>
<author><name sortKey="Palese, P" uniqKey="Palese P">P Palese</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Johnston, Ja" uniqKey="Johnston J">JA Johnston</name>
</author>
<author><name sortKey="Tincher, Lb" uniqKey="Tincher L">LB Tincher</name>
</author>
<author><name sortKey="Lowe, Dk" uniqKey="Lowe D">DK Lowe</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Haber, P" uniqKey="Haber P">P Haber</name>
</author>
<author><name sortKey="Moro, Pl" uniqKey="Moro P">PL Moro</name>
</author>
<author><name sortKey="Mcneil, Mm" uniqKey="Mcneil M">MM McNeil</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Prutsky, Gj" uniqKey="Prutsky G">GJ Prutsky</name>
</author>
<author><name sortKey="Domecq, Jp" uniqKey="Domecq J">JP Domecq</name>
</author>
<author><name sortKey="Elraiyah, T" uniqKey="Elraiyah T">T Elraiyah</name>
</author>
<author><name sortKey="Prokop, Lj" uniqKey="Prokop L">LJ Prokop</name>
</author>
<author><name sortKey="Murad, Mh" uniqKey="Murad M">MH Murad</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jefferson, T" uniqKey="Jefferson T">T Jefferson</name>
</author>
<author><name sortKey="Di Pietrantonj, C" uniqKey="Di Pietrantonj C">C Di Pietrantonj</name>
</author>
<author><name sortKey="Al Ansary, La" uniqKey="Al Ansary L">LA Al-Ansary</name>
</author>
<author><name sortKey="Ferroni, E" uniqKey="Ferroni E">E Ferroni</name>
</author>
<author><name sortKey="Thorning, S" uniqKey="Thorning S">S Thorning</name>
</author>
<author><name sortKey="Thomas, Re" uniqKey="Thomas R">RE Thomas</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jefferson, T" uniqKey="Jefferson T">T Jefferson</name>
</author>
<author><name sortKey="Rivetti, A" uniqKey="Rivetti A">A Rivetti</name>
</author>
<author><name sortKey="Di Pietrantonj, C" uniqKey="Di Pietrantonj C">C Di Pietrantonj</name>
</author>
<author><name sortKey="Demicheli, V" uniqKey="Demicheli V">V Demicheli</name>
</author>
<author><name sortKey="Ferroni, E" uniqKey="Ferroni E">E Ferroni</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Govaert, Tm" uniqKey="Govaert T">TM Govaert</name>
</author>
<author><name sortKey="Thijs, Ct" uniqKey="Thijs C">CT Thijs</name>
</author>
<author><name sortKey="Masurel, N" uniqKey="Masurel N">N Masurel</name>
</author>
<author><name sortKey="Sprenger, Mj" uniqKey="Sprenger M">MJ Sprenger</name>
</author>
<author><name sortKey="Dinant, Gj" uniqKey="Dinant G">GJ Dinant</name>
</author>
<author><name sortKey="Knottnerus, Ja" uniqKey="Knottnerus J">JA Knottnerus</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thompson, Ww" uniqKey="Thompson W">WW Thompson</name>
</author>
<author><name sortKey="Shay, Dk" uniqKey="Shay D">DK Shay</name>
</author>
<author><name sortKey="Weintraub, E" uniqKey="Weintraub E">E Weintraub</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Warfield, Kl" uniqKey="Warfield K">KL Warfield</name>
</author>
<author><name sortKey="Swenson, Dl" uniqKey="Swenson D">DL Swenson</name>
</author>
<author><name sortKey="Olinger, Gg" uniqKey="Olinger G">GG Olinger</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sharma, A" uniqKey="Sharma A">A Sharma</name>
</author>
<author><name sortKey="Gupta, P" uniqKey="Gupta P">P Gupta</name>
</author>
<author><name sortKey="Maheshwari, Rk" uniqKey="Maheshwari R">RK Maheshwari</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nagayama, A" uniqKey="Nagayama A">A Nagayama</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kap, M" uniqKey="Kap M">M Kap</name>
</author>
<author><name sortKey="Arron, Gi" uniqKey="Arron G">GI Arron</name>
</author>
<author><name sortKey="Loibner, M" uniqKey="Loibner M">M Loibner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fedorova, Aa" uniqKey="Fedorova A">AA Fedorova</name>
</author>
<author><name sortKey="Azzami, K" uniqKey="Azzami K">K Azzami</name>
</author>
<author><name sortKey="Ryabchikova, Ei" uniqKey="Ryabchikova E">EI Ryabchikova</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dumard, Ch" uniqKey="Dumard C">CH Dumard</name>
</author>
<author><name sortKey="Barroso, Sp" uniqKey="Barroso S">SP Barroso</name>
</author>
<author><name sortKey="De Oliveira, Ga" uniqKey="De Oliveira G">GA de Oliveira</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dembinski, Jl" uniqKey="Dembinski J">JL Dembinski</name>
</author>
<author><name sortKey="Hungnes, O" uniqKey="Hungnes O">O Hungnes</name>
</author>
<author><name sortKey="Hauge, Ag" uniqKey="Hauge A">AG Hauge</name>
</author>
<author><name sortKey="Kristoffersen, Ac" uniqKey="Kristoffersen A">AC Kristoffersen</name>
</author>
<author><name sortKey="Haneberg, B" uniqKey="Haneberg B">B Haneberg</name>
</author>
<author><name sortKey="Mjaaland, S" uniqKey="Mjaaland S">S Mjaaland</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Belanger, Jm" uniqKey="Belanger J">JM Belanger</name>
</author>
<author><name sortKey="Raviv, Y" uniqKey="Raviv Y">Y Raviv</name>
</author>
<author><name sortKey="Viard, M" uniqKey="Viard M">M Viard</name>
</author>
<author><name sortKey="De La Cruz, Mj" uniqKey="De La Cruz M">MJ de la Cruz</name>
</author>
<author><name sortKey="Nagashima, K" uniqKey="Nagashima K">K Nagashima</name>
</author>
<author><name sortKey="Blumenthal, R" uniqKey="Blumenthal R">R Blumenthal</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ada, G" uniqKey="Ada G">G Ada</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mullbacher, A" uniqKey="Mullbacher A">A Mullbacher</name>
</author>
<author><name sortKey="Ada, Gl" uniqKey="Ada G">GL Ada</name>
</author>
<author><name sortKey="Hla, Rt" uniqKey="Hla R">RT Hla</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mullbacher, A" uniqKey="Mullbacher A">A Mullbacher</name>
</author>
<author><name sortKey="Marshall, Id" uniqKey="Marshall I">ID Marshall</name>
</author>
<author><name sortKey="Blanden, Rv" uniqKey="Blanden R">RV Blanden</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mullbacher, A" uniqKey="Mullbacher A">A Mullbacher</name>
</author>
<author><name sortKey="Marshall, Id" uniqKey="Marshall I">ID Marshall</name>
</author>
<author><name sortKey="Ferris, P" uniqKey="Ferris P">P Ferris</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Alsharifi, M" uniqKey="Alsharifi M">M Alsharifi</name>
</author>
<author><name sortKey="Mullbacher, A" uniqKey="Mullbacher A">A Mullbacher</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Putkonen, P" uniqKey="Putkonen P">P Putkonen</name>
</author>
<author><name sortKey="Thorstensson, R" uniqKey="Thorstensson R">R Thorstensson</name>
</author>
<author><name sortKey="Cranage, M" uniqKey="Cranage M">M Cranage</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Murphey Corb, M" uniqKey="Murphey Corb M">M Murphey-Corb</name>
</author>
<author><name sortKey="Martin, Ln" uniqKey="Martin L">LN Martin</name>
</author>
<author><name sortKey="Davison Fairburn, B" uniqKey="Davison Fairburn B">B Davison-Fairburn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Trauger, R" uniqKey="Trauger R">R Trauger</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Churdboonchart, V" uniqKey="Churdboonchart V">V Churdboonchart</name>
</author>
<author><name sortKey="Sakondhavat, C" uniqKey="Sakondhavat C">C Sakondhavat</name>
</author>
<author><name sortKey="Kulpradist, S" uniqKey="Kulpradist S">S Kulpradist</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Moss, Rb" uniqKey="Moss R">RB Moss</name>
</author>
<author><name sortKey="Giermakowska, W" uniqKey="Giermakowska W">W Giermakowska</name>
</author>
<author><name sortKey="Lanza, P" uniqKey="Lanza P">P Lanza</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kang, Cy" uniqKey="Kang C">CY Kang</name>
</author>
<author><name sortKey="Michalski, C" uniqKey="Michalski C">C Michalski</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rossio, Jl" uniqKey="Rossio J">JL Rossio</name>
</author>
<author><name sortKey="Esser, Mt" uniqKey="Esser M">MT Esser</name>
</author>
<author><name sortKey="Suryanarayana, K" uniqKey="Suryanarayana K">K Suryanarayana</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sheppard, Hw" uniqKey="Sheppard H">HW Sheppard</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Patel, Ss" uniqKey="Patel S">SS Patel</name>
</author>
<author><name sortKey="Wagstaff, Aj" uniqKey="Wagstaff A">AJ Wagstaff</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cherry, Jd" uniqKey="Cherry J">JD Cherry</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Grabenstein, Jd" uniqKey="Grabenstein J">JD Grabenstein</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Buddle, Bm" uniqKey="Buddle B">BM Buddle</name>
</author>
<author><name sortKey="Aldwell, Fe" uniqKey="Aldwell F">FE Aldwell</name>
</author>
<author><name sortKey="Skinner, Ma" uniqKey="Skinner M">MA Skinner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Secanella Fandos, S" uniqKey="Secanella Fandos S">S Secanella-Fandos</name>
</author>
<author><name sortKey="Noguera Ortega, E" uniqKey="Noguera Ortega E">E Noguera-Ortega</name>
</author>
<author><name sortKey="Olivares, F" uniqKey="Olivares F">F Olivares</name>
</author>
<author><name sortKey="Luquin, M" uniqKey="Luquin M">M Luquin</name>
</author>
<author><name sortKey="Julian, E" uniqKey="Julian E">E Julian</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sanakkayala, N" uniqKey="Sanakkayala N">N Sanakkayala</name>
</author>
<author><name sortKey="Sokolovska, A" uniqKey="Sokolovska A">A Sokolovska</name>
</author>
<author><name sortKey="Gulani, J" uniqKey="Gulani J">J Gulani</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yamamoto, T" uniqKey="Yamamoto T">T Yamamoto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kabir, S" uniqKey="Kabir S">S Kabir</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Pasnik, Dj" uniqKey="Pasnik D">DJ Pasnik</name>
</author>
<author><name sortKey="Evans, Jj" uniqKey="Evans J">JJ Evans</name>
</author>
<author><name sortKey="Klesius, Ph" uniqKey="Klesius P">PH Klesius</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tuasikal, Bj" uniqKey="Tuasikal B">BJ Tuasikal</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tuasikal, Bj" uniqKey="Tuasikal B">BJ Tuasikal</name>
</author>
<author><name sortKey="Wibawan, Iw" uniqKey="Wibawan I">IW Wibawan</name>
</author>
<author><name sortKey="Pasaribu, Fh" uniqKey="Pasaribu F">FH Pasaribu</name>
</author>
<author><name sortKey="Estuningsih, S" uniqKey="Estuningsih S">S Estuningsih</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gaidamakova, Ek" uniqKey="Gaidamakova E">EK Gaidamakova</name>
</author>
<author><name sortKey="Myles, Ia" uniqKey="Myles I">IA Myles</name>
</author>
<author><name sortKey="Mcdaniel, Dp" uniqKey="Mcdaniel D">DP McDaniel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Diemen, Pm" uniqKey="Van Diemen P">PM van Diemen</name>
</author>
<author><name sortKey="Yamaguchi, Y" uniqKey="Yamaguchi Y">Y Yamaguchi</name>
</author>
<author><name sortKey="Paterson, Gk" uniqKey="Paterson G">GK Paterson</name>
</author>
<author><name sortKey="Rollier, Cs" uniqKey="Rollier C">CS Rollier</name>
</author>
<author><name sortKey="Hill, Av" uniqKey="Hill A">AV Hill</name>
</author>
<author><name sortKey="Wyllie, Dh" uniqKey="Wyllie D">DH Wyllie</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Burnside, K" uniqKey="Burnside K">K Burnside</name>
</author>
<author><name sortKey="Lembo, A" uniqKey="Lembo A">A Lembo</name>
</author>
<author><name sortKey="Harrell, Mi" uniqKey="Harrell M">MI Harrell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Malley, R" uniqKey="Malley R">R Malley</name>
</author>
<author><name sortKey="Srivastava, A" uniqKey="Srivastava A">A Srivastava</name>
</author>
<author><name sortKey="Lipsitch, M" uniqKey="Lipsitch M">M Lipsitch</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Malley, R" uniqKey="Malley R">R Malley</name>
</author>
<author><name sortKey="Lipsitch, M" uniqKey="Lipsitch M">M Lipsitch</name>
</author>
<author><name sortKey="Stack, A" uniqKey="Stack A">A Stack</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kim, Sb" uniqKey="Kim S">SB Kim</name>
</author>
<author><name sortKey="Kim, Sj" uniqKey="Kim S">SJ Kim</name>
</author>
<author><name sortKey="Lee, Bm" uniqKey="Lee B">BM Lee</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rahman, Mm" uniqKey="Rahman M">MM Rahman</name>
</author>
<author><name sortKey="Uyangaa, E" uniqKey="Uyangaa E">E Uyangaa</name>
</author>
<author><name sortKey="Han, Yw" uniqKey="Han Y">YW Han</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Eldar, A" uniqKey="Eldar A">A Eldar</name>
</author>
<author><name sortKey="Shapiro, O" uniqKey="Shapiro O">O Shapiro</name>
</author>
<author><name sortKey="Bejerano, Y" uniqKey="Bejerano Y">Y Bejerano</name>
</author>
<author><name sortKey="Bercovier, H" uniqKey="Bercovier H">H Bercovier</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liberman, C" uniqKey="Liberman C">C Liberman</name>
</author>
<author><name sortKey="Takagi, M" uniqKey="Takagi M">M Takagi</name>
</author>
<author><name sortKey="Cabrera Crespo, J" uniqKey="Cabrera Crespo J">J Cabrera-Crespo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chawla, S" uniqKey="Chawla S">S Chawla</name>
</author>
<author><name sortKey="Garg, D" uniqKey="Garg D">D Garg</name>
</author>
<author><name sortKey="Jain, Rb" uniqKey="Jain R">RB Jain</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kaufmann, Sh" uniqKey="Kaufmann S">SH Kaufmann</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kaufmann, Sh" uniqKey="Kaufmann S">SH Kaufmann</name>
</author>
<author><name sortKey="Lange, C" uniqKey="Lange C">C Lange</name>
</author>
<author><name sortKey="Rao, M" uniqKey="Rao M">M Rao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cha, Sb" uniqKey="Cha S">SB Cha</name>
</author>
<author><name sortKey="Shin, Sj" uniqKey="Shin S">SJ Shin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="White, Ad" uniqKey="White A">AD White</name>
</author>
<author><name sortKey="Sibley, L" uniqKey="Sibley L">L Sibley</name>
</author>
<author><name sortKey="Dennis, Mj" uniqKey="Dennis M">MJ Dennis</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Davids, V" uniqKey="Davids V">V Davids</name>
</author>
<author><name sortKey="Hanekom, W" uniqKey="Hanekom W">W Hanekom</name>
</author>
<author><name sortKey="Gelderbloem, Sj" uniqKey="Gelderbloem S">SJ Gelderbloem</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mcshane, H" uniqKey="Mcshane H">H McShane</name>
</author>
<author><name sortKey="Williams, A" uniqKey="Williams A">A Williams</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Da Costa, C" uniqKey="Da Costa C">C da Costa</name>
</author>
<author><name sortKey="Walker, B" uniqKey="Walker B">B Walker</name>
</author>
<author><name sortKey="Bonavia, A" uniqKey="Bonavia A">A Bonavia</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mayo, Re" uniqKey="Mayo R">RE Mayo</name>
</author>
<author><name sortKey="Stanford, Jl" uniqKey="Stanford J">JL Stanford</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Von Reyn, Cf" uniqKey="Von Reyn C">CF von Reyn</name>
</author>
<author><name sortKey="Mtei, L" uniqKey="Mtei L">L Mtei</name>
</author>
<author><name sortKey="Arbeit, Rd" uniqKey="Arbeit R">RD Arbeit</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Johnson, Jl" uniqKey="Johnson J">JL Johnson</name>
</author>
<author><name sortKey="Kamya, Rm" uniqKey="Kamya R">RM Kamya</name>
</author>
<author><name sortKey="Okwera, A" uniqKey="Okwera A">A Okwera</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Olson, Bj" uniqKey="Olson B">BJ Olson</name>
</author>
<author><name sortKey="Habel, K" uniqKey="Habel K">K Habel</name>
</author>
<author><name sortKey="Piggott, Wr" uniqKey="Piggott W">WR Piggott</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Paterson, Jc" uniqKey="Paterson J">JC Paterson</name>
</author>
<author><name sortKey="Crombie, Dw" uniqKey="Crombie D">DW Crombie</name>
</author>
<author><name sortKey="Coles, Jc" uniqKey="Coles J">JC Coles</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="O Brien, Kl" uniqKey="O Brien K">KL O'Brien</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dagan, R" uniqKey="Dagan R">R Dagan</name>
</author>
<author><name sortKey="Juergens, C" uniqKey="Juergens C">C Juergens</name>
</author>
<author><name sortKey="Trammel, J" uniqKey="Trammel J">J Trammel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chapman, Ke" uniqKey="Chapman K">KE Chapman</name>
</author>
<author><name sortKey="Wilson, D" uniqKey="Wilson D">D Wilson</name>
</author>
<author><name sortKey="Gorton, R" uniqKey="Gorton R">R Gorton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Goncalves, Vm" uniqKey="Goncalves V">VM Goncalves</name>
</author>
<author><name sortKey="Dias, Wo" uniqKey="Dias W">WO Dias</name>
</author>
<author><name sortKey="Campos, Ib" uniqKey="Campos I">IB Campos</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Moffitt, Kl" uniqKey="Moffitt K">KL Moffitt</name>
</author>
<author><name sortKey="Yadav, P" uniqKey="Yadav P">P Yadav</name>
</author>
<author><name sortKey="Weinberger, Dm" uniqKey="Weinberger D">DM Weinberger</name>
</author>
<author><name sortKey="Anderson, Pw" uniqKey="Anderson P">PW Anderson</name>
</author>
<author><name sortKey="Malley, R" uniqKey="Malley R">R Malley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lu, Yj" uniqKey="Lu Y">YJ Lu</name>
</author>
<author><name sortKey="Leite, L" uniqKey="Leite L">L Leite</name>
</author>
<author><name sortKey="Goncalves, Vm" uniqKey="Goncalves V">VM Goncalves</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Coburn, B" uniqKey="Coburn B">B Coburn</name>
</author>
<author><name sortKey="Grassl, Ga" uniqKey="Grassl G">GA Grassl</name>
</author>
<author><name sortKey="Finlay, Bb" uniqKey="Finlay B">BB Finlay</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kim, K" uniqKey="Kim K">K Kim</name>
</author>
<author><name sortKey="Shim, J" uniqKey="Shim J">J Shim</name>
</author>
<author><name sortKey="Park, S" uniqKey="Park S">S Park</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Previte, Jj" uniqKey="Previte J">JJ Previte</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dima, Fv" uniqKey="Dima F">FV Dima</name>
</author>
<author><name sortKey="Ivanov, D" uniqKey="Ivanov D">D Ivanov</name>
</author>
<author><name sortKey="Dima, Sv" uniqKey="Dima S">SV Dima</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Begum, Rh" uniqKey="Begum R">RH Begum</name>
</author>
<author><name sortKey="Rahman, H" uniqKey="Rahman H">H Rahman</name>
</author>
<author><name sortKey="Ahmed, G" uniqKey="Ahmed G">G Ahmed</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Elzer, Ph" uniqKey="Elzer P">PH Elzer</name>
</author>
<author><name sortKey="Edmonds, Md" uniqKey="Edmonds M">MD Edmonds</name>
</author>
<author><name sortKey="Hagius, Sd" uniqKey="Hagius S">SD Hagius</name>
</author>
<author><name sortKey="Walker, Jv" uniqKey="Walker J">JV Walker</name>
</author>
<author><name sortKey="Gilsdorf, Mj" uniqKey="Gilsdorf M">MJ Gilsdorf</name>
</author>
<author><name sortKey="Davis, Ds" uniqKey="Davis D">DS Davis</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Olsen, Sc" uniqKey="Olsen S">SC Olsen</name>
</author>
<author><name sortKey="Holland, Sd" uniqKey="Holland S">SD Holland</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ahn, Th" uniqKey="Ahn T">TH Ahn</name>
</author>
<author><name sortKey="Nishihara, H" uniqKey="Nishihara H">H Nishihara</name>
</author>
<author><name sortKey="Carpenter, Cm" uniqKey="Carpenter C">CM Carpenter</name>
</author>
<author><name sortKey="Taplin, Gv" uniqKey="Taplin G">GV Taplin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nishihara, H" uniqKey="Nishihara H">H Nishihara</name>
</author>
<author><name sortKey="Ahn, Th" uniqKey="Ahn T">TH Ahn</name>
</author>
<author><name sortKey="Taplin, Gv" uniqKey="Taplin G">GV Taplin</name>
</author>
<author><name sortKey="Carpenter, Cm" uniqKey="Carpenter C">CM Carpenter</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Oliveira, Sc" uniqKey="Oliveira S">SC Oliveira</name>
</author>
<author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y Zhu</name>
</author>
<author><name sortKey="Splitter, Ga" uniqKey="Splitter G">GA Splitter</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Surendran, N" uniqKey="Surendran N">N Surendran</name>
</author>
<author><name sortKey="Hiltbold, Em" uniqKey="Hiltbold E">EM Hiltbold</name>
</author>
<author><name sortKey="Heid, B" uniqKey="Heid B">B Heid</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Moustafa, D" uniqKey="Moustafa D">D Moustafa</name>
</author>
<author><name sortKey="Garg, Vk" uniqKey="Garg V">VK Garg</name>
</author>
<author><name sortKey="Jain, N" uniqKey="Jain N">N Jain</name>
</author>
<author><name sortKey="Sriranganathan, N" uniqKey="Sriranganathan N">N Sriranganathan</name>
</author>
<author><name sortKey="Vemulapalli, R" uniqKey="Vemulapalli R">R Vemulapalli</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dabral, N" uniqKey="Dabral N">N Dabral</name>
</author>
<author><name sortKey="Martha Moreno, L" uniqKey="Martha Moreno L">L Martha Moreno</name>
</author>
<author><name sortKey="Sriranganathan, N" uniqKey="Sriranganathan N">N Sriranganathan</name>
</author>
<author><name sortKey="Vemulapalli, R" uniqKey="Vemulapalli R">R Vemulapalli</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gething, Pw" uniqKey="Gething P">PW Gething</name>
</author>
<author><name sortKey="Patil, Ap" uniqKey="Patil A">AP Patil</name>
</author>
<author><name sortKey="Smith, Dl" uniqKey="Smith D">DL Smith</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schwartz, L" uniqKey="Schwartz L">L Schwartz</name>
</author>
<author><name sortKey="Brown, Gv" uniqKey="Brown G">GV Brown</name>
</author>
<author><name sortKey="Genton, B" uniqKey="Genton B">B Genton</name>
</author>
<author><name sortKey="Moorthy, Vs" uniqKey="Moorthy V">VS Moorthy</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Okie, S" uniqKey="Okie S">S Okie</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Agnandji, St" uniqKey="Agnandji S">ST Agnandji</name>
</author>
<author><name sortKey="Lell, B" uniqKey="Lell B">B Lell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Russell, Pf" uniqKey="Russell P">PF Russell</name>
</author>
<author><name sortKey="Mohan, Bn" uniqKey="Mohan B">BN Mohan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nussenzweig, Rs" uniqKey="Nussenzweig R">RS Nussenzweig</name>
</author>
<author><name sortKey="Vanderberg, J" uniqKey="Vanderberg J">J Vanderberg</name>
</author>
<author><name sortKey="Most, H" uniqKey="Most H">H Most</name>
</author>
<author><name sortKey="Orton, C" uniqKey="Orton C">C Orton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hoffman, Sl" uniqKey="Hoffman S">SL Hoffman</name>
</author>
<author><name sortKey="Goh, Lm" uniqKey="Goh L">LM Goh</name>
</author>
<author><name sortKey="Luke, Tc" uniqKey="Luke T">TC Luke</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roestenberg, M" uniqKey="Roestenberg M">M Roestenberg</name>
</author>
<author><name sortKey="Mccall, M" uniqKey="Mccall M">M McCall</name>
</author>
<author><name sortKey="Hopman, J" uniqKey="Hopman J">J Hopman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roestenberg, M" uniqKey="Roestenberg M">M Roestenberg</name>
</author>
<author><name sortKey="Teirlinck, Ac" uniqKey="Teirlinck A">AC Teirlinck</name>
</author>
<author><name sortKey="Mccall, Mb" uniqKey="Mccall M">MB McCall</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Laurens, Mb" uniqKey="Laurens M">MB Laurens</name>
</author>
<author><name sortKey="Billingsley, P" uniqKey="Billingsley P">P Billingsley</name>
</author>
<author><name sortKey="Richman, A" uniqKey="Richman A">A Richman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Seder, Ra" uniqKey="Seder R">RA Seder</name>
</author>
<author><name sortKey="Chang, Lj" uniqKey="Chang L">LJ Chang</name>
</author>
<author><name sortKey="Enama, Me" uniqKey="Enama M">ME Enama</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Epstein, Je" uniqKey="Epstein J">JE Epstein</name>
</author>
<author><name sortKey="Richie, Tl" uniqKey="Richie T">TL Richie</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hoffman, Sl" uniqKey="Hoffman S">SL Hoffman</name>
</author>
<author><name sortKey="Billingsley, Pf" uniqKey="Billingsley P">PF Billingsley</name>
</author>
<author><name sortKey="James, E" uniqKey="James E">E James</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Epstein, Je" uniqKey="Epstein J">JE Epstein</name>
</author>
<author><name sortKey="Tewari, K" uniqKey="Tewari K">K Tewari</name>
</author>
<author><name sortKey="Lyke, Ke" uniqKey="Lyke K">KE Lyke</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anassi, E" uniqKey="Anassi E">E Anassi</name>
</author>
<author><name sortKey="Ndefo, Ua" uniqKey="Ndefo U">UA Ndefo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Walls, B" uniqKey="Walls B">B Walls</name>
</author>
<author><name sortKey="Jordan, L" uniqKey="Jordan L">L Jordan</name>
</author>
<author><name sortKey="Diaz, L" uniqKey="Diaz L">L Diaz</name>
</author>
<author><name sortKey="Miller, R" uniqKey="Miller R">R Miller</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Iacovelli, R" uniqKey="Iacovelli R">R Iacovelli</name>
</author>
<author><name sortKey="Pietrantonio, F" uniqKey="Pietrantonio F">F Pietrantonio</name>
</author>
<author><name sortKey="Farcomeni, A" uniqKey="Farcomeni A">A Farcomeni</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jansman, Fg" uniqKey="Jansman F">FG Jansman</name>
</author>
<author><name sortKey="Sleijfer, Dt" uniqKey="Sleijfer D">DT Sleijfer</name>
</author>
<author><name sortKey="De Graaf, Jc" uniqKey="De Graaf J">JC de Graaf</name>
</author>
<author><name sortKey="Coenen, Jl" uniqKey="Coenen J">JL Coenen</name>
</author>
<author><name sortKey="Brouwers, Jr" uniqKey="Brouwers J">JR Brouwers</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cortes, J" uniqKey="Cortes J">J Cortes</name>
</author>
<author><name sortKey="Calvo, V" uniqKey="Calvo V">V Calvo</name>
</author>
<author><name sortKey="Ramirez Merino, N" uniqKey="Ramirez Merino N">N Ramirez-Merino</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cartwright, Th" uniqKey="Cartwright T">TH Cartwright</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thomay, Aa" uniqKey="Thomay A">AA Thomay</name>
</author>
<author><name sortKey="Nagorney, Dm" uniqKey="Nagorney D">DM Nagorney</name>
</author>
<author><name sortKey="Cohen, Sj" uniqKey="Cohen S">SJ Cohen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Peng, Sl" uniqKey="Peng S">SL Peng</name>
</author>
<author><name sortKey="Thomas, M" uniqKey="Thomas M">M Thomas</name>
</author>
<author><name sortKey="Ruszkiewicz, A" uniqKey="Ruszkiewicz A">A Ruszkiewicz</name>
</author>
<author><name sortKey="Hunter, A" uniqKey="Hunter A">A Hunter</name>
</author>
<author><name sortKey="Lawrence, M" uniqKey="Lawrence M">M Lawrence</name>
</author>
<author><name sortKey="Moore, J" uniqKey="Moore J">J Moore</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Duncan, W" uniqKey="Duncan W">W Duncan</name>
</author>
<author><name sortKey="Macdougall, Rh" uniqKey="Macdougall R">RH MacDougall</name>
</author>
<author><name sortKey="Kerr, Gr" uniqKey="Kerr G">GR Kerr</name>
</author>
<author><name sortKey="Downing, D" uniqKey="Downing D">D Downing</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rades, D" uniqKey="Rades D">D Rades</name>
</author>
<author><name sortKey="Fehlauer, F" uniqKey="Fehlauer F">F Fehlauer</name>
</author>
<author><name sortKey="Bajrovic, A" uniqKey="Bajrovic A">A Bajrovic</name>
</author>
<author><name sortKey="Mahlmann, B" uniqKey="Mahlmann B">B Mahlmann</name>
</author>
<author><name sortKey="Richter, E" uniqKey="Richter E">E Richter</name>
</author>
<author><name sortKey="Alberti, W" uniqKey="Alberti W">W Alberti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kerns, Sl" uniqKey="Kerns S">SL Kerns</name>
</author>
<author><name sortKey="Ostrer, H" uniqKey="Ostrer H">H Ostrer</name>
</author>
<author><name sortKey="Rosenstein, Bs" uniqKey="Rosenstein B">BS Rosenstein</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Palucka, K" uniqKey="Palucka K">K Palucka</name>
</author>
<author><name sortKey="Banchereau, J" uniqKey="Banchereau J">J Banchereau</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Patel, Ph" uniqKey="Patel P">PH Patel</name>
</author>
<author><name sortKey="Kockler, Dr" uniqKey="Kockler D">DR Kockler</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Small, Ej" uniqKey="Small E">EJ Small</name>
</author>
<author><name sortKey="Schellhammer, Pf" uniqKey="Schellhammer P">PF Schellhammer</name>
</author>
<author><name sortKey="Higano, Cs" uniqKey="Higano C">CS Higano</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kantoff, Pw" uniqKey="Kantoff P">PW Kantoff</name>
</author>
<author><name sortKey="Higano, Cs" uniqKey="Higano C">CS Higano</name>
</author>
<author><name sortKey="Shore, Nd" uniqKey="Shore N">ND Shore</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nemunaitis, J" uniqKey="Nemunaitis J">J Nemunaitis</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dummer, R" uniqKey="Dummer R">R Dummer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Geary, Sm" uniqKey="Geary S">SM Geary</name>
</author>
<author><name sortKey="Lemke, Cd" uniqKey="Lemke C">CD Lemke</name>
</author>
<author><name sortKey="Lubaroff, Dm" uniqKey="Lubaroff D">DM Lubaroff</name>
</author>
<author><name sortKey="Salem, Ak" uniqKey="Salem A">AK Salem</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Callahan, Mk" uniqKey="Callahan M">MK Callahan</name>
</author>
<author><name sortKey="Wolchok, Jd" uniqKey="Wolchok J">JD Wolchok</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Clin Exp Vaccine Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Clin Exp Vaccine Res</journal-id>
<journal-id journal-id-type="publisher-id">CEVR</journal-id>
<journal-title-group><journal-title>Clinical and Experimental Vaccine Research</journal-title>
</journal-title-group>
<issn pub-type="ppub">2287-3651</issn>
<issn pub-type="epub">2287-366X</issn>
<publisher><publisher-name>The Korean Vaccine Society</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26273573</article-id>
<article-id pub-id-type="pmc">4524899</article-id>
<article-id pub-id-type="doi">10.7774/cevr.2015.4.2.145</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Application of radiation technology in vaccines development</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Seo</surname>
<given-names>Ho Seong</given-names>
</name>
<xref ref-type="aff" rid="A1"></xref>
</contrib>
</contrib-group>
<aff id="A1">Radiation Biotechnology Research Division, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Korea.</aff>
<author-notes><corresp>Corresponding author: Ho Seong Seo, PhD. Radiation Biotechnology Research Division (136A), Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Genmgu-gil, Jeongeup 580-185, Korea. Tel: +82-63-570-3140, Fax: +82-63-570-3149, <email>hoseongseo@kaeri.re.kr</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>7</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub"><day>29</day>
<month>7</month>
<year>2015</year>
</pub-date>
<volume>4</volume>
<issue>2</issue>
<fpage>145</fpage>
<lpage>158</lpage>
<history><date date-type="received"><day>13</day>
<month>5</month>
<year>2015</year>
</date>
<date date-type="rev-recd"><day>10</day>
<month>6</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>20</day>
<month>6</month>
<year>2015</year>
</date>
</history>
<permissions><copyright-statement>© Korean Vaccine Society.</copyright-statement>
<copyright-year>2015</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link>
) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract><p>One of the earliest methods used in the manufacture of stable and safe vaccines is the use of chemical and physical treatments to produce inactivated forms of pathogens. Although these types of vaccines have been successful in eliciting specific humoral immune responses to pathogen-associated immunogens, there is a large demand for the development of fast, safe, and effective vaccine manufacturing strategies. Radiation sterilization has been used to develop a variety of vaccine types, because it can eradicate chemical contaminants and penetrate pathogens to destroy nucleic acids without damaging the pathogen surface antigens. Nevertheless, irradiated vaccines have not widely been used at an industrial level because of difficulties obtaining the necessary equipment. Recent successful clinical trials of irradiated vaccines against pathogens and tumors have led to a reevaluation of radiation technology as an alternative method to produce vaccines. In the present article, we review the challenges associated with creating irradiated vaccines and discuss potential strategies for developing vaccines using radiation technology.</p>
</abstract>
<kwd-group><kwd>Gamma-radiation</kwd>
<kwd>Irradiated vaccine</kwd>
<kwd>GVAX</kwd>
<kwd>Killed vaccine</kwd>
</kwd-group>
</article-meta>
</front>
<body><sec><title>Radiation and Vaccines</title>
<p>Radiation is the emission or transmission of energy in the form of waves (ionizing radiation) or electron particles (non-ionizing radiation) [<xref rid="B1" ref-type="bibr">1</xref>
]. The use of ionizing radiation, including X-rays and gamma rays, has increased substantially over the last 30 years in both medicine and industry [<xref rid="B2" ref-type="bibr">2</xref>
<xref rid="B3" ref-type="bibr">3</xref>
<xref rid="B4" ref-type="bibr">4</xref>
<xref rid="B5" ref-type="bibr">5</xref>
]. In addition to its initial applications in the diagnosis and treatment of disease, radiation technology has expanded into other areas such as crop breeding, sterilization of food, polymer processing, and processing of environmental pollutants [<xref rid="B6" ref-type="bibr">6</xref>
<xref rid="B7" ref-type="bibr">7</xref>
<xref rid="B8" ref-type="bibr">8</xref>
<xref rid="B9" ref-type="bibr">9</xref>
]. Radiation technology has also been used in the development of human and animal vaccines, especially in the sterilization and generation of random mutations.</p>
<p>Many vaccines used today rely on technologies developed over 100 years ago, and involve some form of attenuation (i.e., the use of an alternative or mutant strain of pathogenic organism with reduced virulence that maintains its immunogenicity, or inactivation, where chemical or physical methods are used to kill virulent pathogenic strains) [<xref rid="B10" ref-type="bibr">10</xref>
<xref rid="B11" ref-type="bibr">11</xref>
<xref rid="B12" ref-type="bibr">12</xref>
<xref rid="B13" ref-type="bibr">13</xref>
]. These vaccines have been extremely successful in protecting against animal and human diseases caused by viruses and bacteria. Smallpox and Rinderpest have now been successfully eradicated throughout the world since the introduction of vaccines [<xref rid="B14" ref-type="bibr">14</xref>
<xref rid="B15" ref-type="bibr">15</xref>
<xref rid="B16" ref-type="bibr">16</xref>
<xref rid="B17" ref-type="bibr">17</xref>
]. Nevertheless, the aim remains to maximize the effectiveness and quality of currently available or new vaccines, because current methods of vaccine manufacture are not cost-effective, are susceptible to chemical contamination, are difficult to match to current circulating strains, and are susceptible to other manufacturing issues.</p>
<p>Radiation technology is of interest to vaccine manufacturers, because it can remove chemical contaminants and penetrate pathogens to damage the DNA [<xref rid="B18" ref-type="bibr">18</xref>
<xref rid="B19" ref-type="bibr">19</xref>
]. However, the development of irradiated vaccines has not been pursued avidly over the past 20 years for two main reasons. First, the development of new radiation techniques has been considered impractical or difficult due to issues accessing the radiation equipment. Second, it has been thought that modern subunit vaccines would provide a solution, as they can be developed more easily [<xref rid="B20" ref-type="bibr">20</xref>
]. However, there are several reasons to reevaluate the use of radiated inactivation and attenuation for the production of vaccines [<xref rid="B20" ref-type="bibr">20</xref>
<xref rid="B21" ref-type="bibr">21</xref>
]. The recent successful development of irradiated vaccines for human malaria and influenza have demonstrated the feasibility and practicality of this technique, and have shown that technical problems can be overcome using existing expertise, without needing to resort to sophisticated technology [<xref rid="B22" ref-type="bibr">22</xref>
<xref rid="B23" ref-type="bibr">23</xref>
]. Moreover, this technology has been used to produce an anti-cancer vaccine by inactivating cancer cells [<xref rid="B24" ref-type="bibr">24</xref>
<xref rid="B25" ref-type="bibr">25</xref>
<xref rid="B26" ref-type="bibr">26</xref>
]. In the present review, we discuss several promising candidates for irradiated vaccines that have undergone clinical trials, and assess recent advances in radiation vaccine technologies.</p>
</sec>
<sec><title>Vaccines Based on Inactivated Microorganisms and Tumor Cells</title>
<p>Inactivated vaccines are produced by killing the pathogens with chemicals, heat, or radiation. These vaccines are more stable and safer than live vaccines, as they can be stored and transported in a freeze-dried form that makes them accessible to people in developing countries [<xref rid="B27" ref-type="bibr">27</xref>
<xref rid="B28" ref-type="bibr">28</xref>
]. Formaldehyde, the most common chemical used in vaccine production, was first tested in a vaccine by Madsen [<xref rid="B29" ref-type="bibr">29</xref>
], and was later shown to be successful in preventing several infectious diseases such as typhoid, cholera, poliovirus, hepatitis A, Japanese encephalitis, and tick-borne encephalitis virus [<xref rid="B28" ref-type="bibr">28</xref>
]. However, it can cause irreversible modifications by cross-linking antigens that can damage key antigenic epitopes, leading to reduced immunogenicity or even exacerbated disease following a microbial infection [<xref rid="B30" ref-type="bibr">30</xref>
].</p>
<p>β-Propiolactone (BPL) is also a common inactivation method that was first described in 1955 [<xref rid="B20" ref-type="bibr">20</xref>
]. It is used in the production of influenza and rabies vaccines, and is also used in vaccines currently under development, such as those for <italic>Streptococcus pneumoniae</italic>
. The advantages of this chemical are that it is rapidly neutralized into a nontoxic, noncarcinogenic product by the addition of thiosulphate, and it interacts directly with nucleic acids by inducing DNA double helix cross-linking [<xref rid="B31" ref-type="bibr">31</xref>
]. However, BPL may also interact with amino acids, which contain nucleophilic moieties that induce conformational changes on surface antigens [<xref rid="B32" ref-type="bibr">32</xref>
]. Thus, inactivation of pathogens with BPL may also trigger adverse immune reactions, including the induction of allergic responses through chemical modification of the vaccine components [<xref rid="B33" ref-type="bibr">33</xref>
<xref rid="B34" ref-type="bibr">34</xref>
]. Therefore, there is an increasing demand to identify safe and effective strategies to produce inactivated vaccines, which are crucial for the future of vaccine development.</p>
<p>Radiation inactivation of pathogens has potential applications in sterilization and the manufacture of biological reagents and laboratory supplies [<xref rid="B35" ref-type="bibr">35</xref>
]. Since the 1940s, when ionizing radiation (e.g., gamma rays and X-rays) was introduced for the sterilization of pathogens, vaccine development using irradiation has been extensively investigated [<xref rid="B36" ref-type="bibr">36</xref>
<xref rid="B37" ref-type="bibr">37</xref>
]. The major advantages of ionizing radiation in vaccine development compared to ultraviolet light or chemical agents are its ability to penetrate through most biological materials, and the fact that it targets both double and single stranded nucleic acids while causing less damage to surface antigenic proteins. Moreover, there is no need to remove any chemical residue after inactivation. Although the argument remains that irradiated vaccines elicit different immune responses than those generated by heat-killed or chemically killed methods, the demand for the application of gamma radiation is increasing for the development safe vaccines [<xref rid="B38" ref-type="bibr">38</xref>
<xref rid="B39" ref-type="bibr">39</xref>
<xref rid="B40" ref-type="bibr">40</xref>
].</p>
</sec>
<sec><title>Irradiated Viral Vaccines</title>
<p>Trivalent inactivated or live attenuated influenza vaccines are commonly used worldwide [<xref rid="B11" ref-type="bibr">11</xref>
<xref rid="B41" ref-type="bibr">41</xref>
<xref rid="B42" ref-type="bibr">42</xref>
<xref rid="B43" ref-type="bibr">43</xref>
]. Inactivated influenza vaccine is prepared by treating the virus with a chemical agent that contains either the whole inactivated virus or the active part (split or subunit vaccines) [<xref rid="B11" ref-type="bibr">11</xref>
<xref rid="B43" ref-type="bibr">43</xref>
<xref rid="B44" ref-type="bibr">44</xref>
]. The live attenuated influenza virus has the reduced ability to replicate in human cells, but can still stimulate immune responses [<xref rid="B45" ref-type="bibr">45</xref>
<xref rid="B46" ref-type="bibr">46</xref>
]. Each year, predictions are made of three potential influenza strains for the coming season, which are based on a continuous worldwide surveillance program by the World Health Organization [<xref rid="B42" ref-type="bibr">42</xref>
]. However, most influenza vaccines against any predicted seasonal flu provide only modest protection for the given strains, and have little efficacy in the elderly [<xref rid="B47" ref-type="bibr">47</xref>
<xref rid="B48" ref-type="bibr">48</xref>
<xref rid="B49" ref-type="bibr">49</xref>
<xref rid="B50" ref-type="bibr">50</xref>
]. This is because the influenza vaccine is highly dependent on how well the vaccine strain matches the newly emerging virus. Research is underway to develop a universal vaccine that has a broad coverage of influenza antigenic drift that will not require annual modification [<xref rid="B42" ref-type="bibr">42</xref>
<xref rid="B43" ref-type="bibr">43</xref>
].</p>
<p>Over the last 60 years, the development of new methods of virus inactivation has been explored [<xref rid="B51" ref-type="bibr">51</xref>
<xref rid="B52" ref-type="bibr">52</xref>
<xref rid="B53" ref-type="bibr">53</xref>
<xref rid="B54" ref-type="bibr">54</xref>
<xref rid="B55" ref-type="bibr">55</xref>
<xref rid="B56" ref-type="bibr">56</xref>
<xref rid="B57" ref-type="bibr">57</xref>
<xref rid="B58" ref-type="bibr">58</xref>
<xref rid="B59" ref-type="bibr">59</xref>
]. Gamma radiation inactivation has been suggested as an alternative method for inactivation of virus reproduction, primarily by damaging the nucleic acid while preserving immunogenicity. Mullbacher et al. [<xref rid="B60" ref-type="bibr">60</xref>
] first demonstrated a high cross-protective immune response of irradiated influenza A virus against other influenza A strains. Gamma irradiated influenza vaccine was more effective at priming cross reactive cytotoxic T cells, and protected mice against a heterologous influenza virus [<xref rid="B60" ref-type="bibr">60</xref>
<xref rid="B61" ref-type="bibr">61</xref>
<xref rid="B62" ref-type="bibr">62</xref>
]. Alsharifi and Mullbacher [<xref rid="B63" ref-type="bibr">63</xref>
] showed that a single dose of nonadjuvanted intranasal gamma-irradiated influenza A vaccine (GammaFlu) provided robust protection in mice, which was mainly mediated by cytotoxic T cells. Unlike the chemical inactivation method, gamma irradiation preserved the functional domains of the viral proteins, which facilitated uptake and presentation on major histocompatibility complex class I (MHC-I) of antigen presenting cells. This approach has been tested in pre-clinical studies by Gamma Vaccines Pty (Manuka, ACT, Australia), and is now moving towards a full clinical trial.</p>
<p>A vaccine against the human immunodeficiency virus (HIV) would be highly effective for preventing acquired immunodeficiency syndrome. Because HIV was identified in 1983, significant progress has been made in the development of an HIV vaccine worldwide. However, to date, no vaccine has been fully successful. Initially, subunit vaccines, GP120 (VaxGen Inc., San Francisco, CA, USA) and Ad5 (Merck & Co., Kenilworth, NJ, USA), were approved in clinical trials, but have not shown sufficient efficacy in human subjects. In a recent clinical trial conducted by Sanofi Pasteur (Lyon, France), GP120 carrying the Canarypox virus vaccine showed ~25% improved protection compared to a non-vaccinated group of 60,000 human subjects; however, it was dropped at clinical phase III. Over the past 15 years, several groups have initiated the pre-clinical development of inactivated HIV or simian immunodeficiency virus (SIV) vaccines, which conferred potent serological responses against host cell components incorporated into HIV/SIV virions. Currently, the most promising result has come from two gamma-irradiated whole-killed attenuated HIV vaccines, SAV0001 and Remune [<xref rid="B64" ref-type="bibr">64</xref>
<xref rid="B65" ref-type="bibr">65</xref>
].</p>
<p>Remune, invented by Jonas Salk in 1987 in collaboration with Dr. Dennis Carlo of the Immune Response Corporation (<ext-link ext-link-type="uri" xlink:href="http://www.immuneresponsebiopharma.com">http://www.immuneresponsebiopharma.com</ext-link>
) [<xref rid="B66" ref-type="bibr">66</xref>
<xref rid="B67" ref-type="bibr">67</xref>
], was the first to go to large national trials to ascertain whether it could assist current antivirals by enabling the immune system to control HIV more effectively. This vaccine, derived from an intersubtype recombinant of clade A envelope and clade G Cag, is inactivated through the sequential application of BPL and gamma irradiation. The HIV envelope gp120 glycoprotein is depleted during preparation and inactivation [<xref rid="B68" ref-type="bibr">68</xref>
]. Although a large-scale multi-center phase III trial with HIV patients on antiretroviral therapy showed no significant differences in the incidence of opportunistic infections or death, a statistically significant decline in viral load, increased CD4+ T cell counts, and enhanced HIV-1 specific antibody responses were observed in the subjects treated with Remune.</p>
<p>SAV001 was developed by Dr. Chil-Yong Kang at Western University, Canada [<xref rid="B69" ref-type="bibr">69</xref>
]. This represents the first and only preventive HIV vaccine tested in clinical trials, and is based on a genetically modified killed whole-virus. The <italic>nef</italic>
and <italic>vpu</italic>
genes were deleted in the HIV-1 strain to make the attenuated strain, and the env signal peptide was replaced with the honey bee antimicrobial peptide melittin to enhance viral replication and production. Thus, this genetically modified HIV-1 strain is non-pathogenic, and can be produced in large quantities in a cell culture-based system. It is manufactured as a killed vaccine, by harvesting HIV-1 that is completely inactivated by aldrithiol-2 and sequential gamma irradiation [<xref rid="B70" ref-type="bibr">70</xref>
<xref rid="B71" ref-type="bibr">71</xref>
]. The phase I clinical trial (ClinicalTrials.gov Identifier: NCT01546818) was completed in 2013, and resulted in significant increases in the levels of gp120-specific and P24-specific antibodies, whereas no adverse effects were observed. Phase II/III large multi-center clinical trials on higher risk HIV patients will be conducted shortly.</p>
</sec>
<sec><title>Irradiated Bacterial Whole Cell Vaccines</title>
<p>Since the typhoid vaccine was first introduced as an inactivated bacterial vaccine at the end of the 19th century, the administration of inactivated whole cell bacterial vaccines is one of the most well-studied methods of vaccination against bacterial infections [<xref rid="B20" ref-type="bibr">20</xref>
]. This approach offers several advantages. First, they are naturally occurring microparticles that can carry multiple antigens that can be important in providing protection. Second, this approach is relatively quick and inexpensive to manufacture. Although pertussis and anthrax vaccines are the only current licensed inactivated bacterial vaccine used for immunization of the general public, the demand to develop new inactivated bacterial vaccines for emerging pathogens is increasing [<xref rid="B72" ref-type="bibr">72</xref>
<xref rid="B73" ref-type="bibr">73</xref>
<xref rid="B74" ref-type="bibr">74</xref>
]. Irradiated bacterial vaccines, which prevent replication but retain their metabolic activity, generate higher humoral immune responses and protection against extracellular and intracellular bacteria, including human and animal pathogens (<xref ref-type="table" rid="T1">Table 1</xref>
) [<xref rid="B75" ref-type="bibr">75</xref>
<xref rid="B76" ref-type="bibr">76</xref>
<xref rid="B77" ref-type="bibr">77</xref>
<xref rid="B78" ref-type="bibr">78</xref>
<xref rid="B79" ref-type="bibr">79</xref>
<xref rid="B80" ref-type="bibr">80</xref>
<xref rid="B81" ref-type="bibr">81</xref>
<xref rid="B82" ref-type="bibr">82</xref>
<xref rid="B83" ref-type="bibr">83</xref>
<xref rid="B84" ref-type="bibr">84</xref>
<xref rid="B85" ref-type="bibr">85</xref>
<xref rid="B86" ref-type="bibr">86</xref>
]. Inactivated bacterial vaccines were originally intended for intranasal or oral administration to activate a mucosal immune response [<xref rid="B87" ref-type="bibr">87</xref>
<xref rid="B88" ref-type="bibr">88</xref>
<xref rid="B89" ref-type="bibr">89</xref>
<xref rid="B90" ref-type="bibr">90</xref>
]. Intranasal immunization with inactivated bacterial vaccines elicits serotype independent humoral as well as cellular immune responses [<xref rid="B91" ref-type="bibr">91</xref>
<xref rid="B92" ref-type="bibr">92</xref>
].</p>
<p>Leprosy and tuberculosis are the most common mycobacterial diseases representing a major cause of death worldwide [<xref rid="B93" ref-type="bibr">93</xref>
<xref rid="B94" ref-type="bibr">94</xref>
<xref rid="B95" ref-type="bibr">95</xref>
]. The most effective strategy for treating tuberculosis (TB) is vaccination. Live bacille Calmette-Guerin (BCG), which was introduced in 1921, is the only available vaccine against both diseases [<xref rid="B96" ref-type="bibr">96</xref>
]. Although it provides immunization protection for infants and young adults, it has had inconsistent and unpredictable results in adults, sometimes causing severe allergenic reactions in the skin, and offers less durable protection that often requires a second boosting immunization [<xref rid="B96" ref-type="bibr">96</xref>
<xref rid="B97" ref-type="bibr">97</xref>
]. More than 10 TB vaccines are in the early development stages [<xref rid="B98" ref-type="bibr">98</xref>
<xref rid="B99" ref-type="bibr">99</xref>
<xref rid="B100" ref-type="bibr">100</xref>
]. The most effective clinical results have being obtained using the heat-killed inactivated <italic>Mycobacterium obuense</italic>
vaccine, DAR-901 (ClinicalTrials.gov Identifier: NCT02063555) [<xref rid="B101" ref-type="bibr">101</xref>
<xref rid="B102" ref-type="bibr">102</xref>
<xref rid="B103" ref-type="bibr">103</xref>
]. A trial in Tanzania of >2,000 HIV positive subjects showed it to be both safe and effective. Irradiated killed TB vaccines were first reported by Olson et al. in 1947 [<xref rid="B104" ref-type="bibr">104</xref>
] and Paterson et al. in 1949 [<xref rid="B105" ref-type="bibr">105</xref>
]. Although the irradiated-killed TB vaccine gave a similar degree of protection as the live BCG vaccine in animal models, the allergenic effect was markedly reduced. Because many previous studies have shown that irradiated TB elicits the robust production of antibodies and protection against the challenge of infectious TB, this strategy should be considered an alternative inactivation method for TB whole-cell vaccines (WCVs).</p>
<p><italic>Streptococcus pneumoniae</italic>
is a causative agent in children and older adults. Currently the available polysaccharide conjugate vaccine (PCV) generates serotype-specific antibody responses [<xref rid="B106" ref-type="bibr">106</xref>
<xref rid="B107" ref-type="bibr">107</xref>
]. Phase IV surveillance studies in many countries found an increasing number of non-vaccine serotypes and the appearance of new serotypes [<xref rid="B108" ref-type="bibr">108</xref>
]. Thus, alternative approaches are being considered, such as protein-based vaccines and WCVs. An inactivated whole-cell pneumococcal vaccine has been sought since the beginning of the 20th century. More recently, a collaboration between PATH Vaccine Solutions (Seattle, WA, USA) and Malley's group [<xref rid="B109" ref-type="bibr">109</xref>
<xref rid="B110" ref-type="bibr">110</xref>
] showed successful results using a chemically killed non-encapsulated pneumococcal vaccine in an animal model and in a clinical phase I trial (ClinicalTrials.gov Identifier: NCT01537185) [<xref rid="B93" ref-type="bibr">93</xref>
<xref rid="B111" ref-type="bibr">111</xref>
]. No serious adverse events were reported in these clinical trials, and currently, participants are being recruited to test its safety and tolerability with intramuscular administration in healthy Kenyan adults and toddlers who have been primed with PCV vaccines. We also investigated the possibility of creating an irradiated pneumococcal vaccine using non-encapsulated pneumococci. Irradiated killed pneumococci showed non-toxic effects <italic>in vitro</italic>
, whereas chemically killed pneumonia did (unpublished data). In addition, irradiated WCVs elicited a significantly higher level of antibody responses in mice with intranasal and intramuscular vaccinations (<xref ref-type="fig" rid="F1">Fig. 1</xref>
). This shows that irradiation is one possible method to manufacture a whole killed pneumococcal vaccine.</p>
<p><italic>Salmonella enterica</italic>
causes a variety of infectious diseases in animals and humans [<xref rid="B112" ref-type="bibr">112</xref>
<xref rid="B113" ref-type="bibr">113</xref>
]. Live attenuated vaccines generally confer better protection than killed vaccines; however, they are limited by their toxicity and cause mild diarrhea. Previte [<xref rid="B114" ref-type="bibr">114</xref>
] first described the use of radiation to increase immunogenicity and decrease the toxicity of Salmonella compared to acetone-, alcohol-, and heat-killed vaccines in mouse and bovine salmonellosis models [<xref rid="B115" ref-type="bibr">115</xref>
<xref rid="B116" ref-type="bibr">116</xref>
]. <italic>Brucella</italic>
species (<italic>B. melitensis</italic>
, <italic>B. abortus</italic>
, <italic>B. suis</italic>
) are the causative agents of brucellosis, a chronic bacterial infection in animals and humans. Some live attenuated vaccines (S19, RB51, Rev1) are licensed for use in animals, but not in humans. However, the live vaccine has been implicated in several accidental infections in humans and animals [<xref rid="B117" ref-type="bibr">117</xref>
<xref rid="B118" ref-type="bibr">118</xref>
]. Several inactivated <italic>Brucella</italic>
vaccines have been tested as alternative, safer vaccines. In a mouse model, irradiated <italic>B. abortus</italic>
RB51 and <italic>B. neotomae</italic>
induced protection against systemic and mucosal challenge with <italic>Brucella</italic>
spp. Oral vaccination in mice also elicited the activation of CD4 and CD8+ T lymphocytes specific to infectious <italic>Brucella</italic>
species [<xref rid="B40" ref-type="bibr">40</xref>
<xref rid="B77" ref-type="bibr">77</xref>
<xref rid="B119" ref-type="bibr">119</xref>
<xref rid="B120" ref-type="bibr">120</xref>
<xref rid="B121" ref-type="bibr">121</xref>
<xref rid="B122" ref-type="bibr">122</xref>
<xref rid="B123" ref-type="bibr">123</xref>
<xref rid="B124" ref-type="bibr">124</xref>
].</p>
</sec>
<sec><title>Irradiated Malaria Vaccines</title>
<p>Human malaria is primarily due to infection with one of five Plasmodium species: <italic>Plasmodium falciparum</italic>
, <italic>Plasmodium vivax</italic>
, <italic>Plasmodium malariae</italic>
, <italic>Plasmodium ovale</italic>
, and <italic>Plasmodium knowlesi</italic>
. Of these, <italic>P. falciparum</italic>
is responsible for 92% of deaths that mostly occur in children living in sub-Saharan Africa [<xref rid="B125" ref-type="bibr">125</xref>
]. In 2012 there was an estimated 220 million clinical cases and 0.63 million deaths worldwide from malaria infection [<xref rid="B23" ref-type="bibr">23</xref>
]. An effective vaccine for <italic>P. falciparum</italic>
is needed for use in malaria-endemic populations, but no licensed malaria vaccines and candidates have consistently produced a protective level of efficacy [<xref rid="B126" ref-type="bibr">126</xref>
].</p>
<p>Based on the life cycle of the malaria parasite and the process of infection, malaria vaccines are divided into four potential target groups; interruption of human to mosquito transmission (parasite sexual and mosquito stages), inhibition of clinical consequences (asexual blood stage), prevention of mosquito to human transmission, and pre-erythrocytic infections (sporozoite [SPZ]/liver stages) [<xref rid="B127" ref-type="bibr">127</xref>
]. Among them, only vaccines targeting pre-erythrocytic infections showed any significant levels of protection in human clinical trials [<xref rid="B128" ref-type="bibr">128</xref>
]. The RTS,S/AS01 subunit vaccine consisting of the <italic>P. falciparum</italic>
circumsporozoite protein (CSP) fused with the hepatitis B surface antigen (HBsAg) is one of most advanced anti-malaria vaccines at a clinical level. Although this vaccine did not appear to elicit a CD8+ T cell response, CSP-HBsAg induced a specific CD4+ T cell response targeting the whole SPZ. A large-scale clinical phase III trial (ClinicalTrials.gov Identifier: NCT00866619) in African infants aged 6-8 weeks showed that RTS,S/A01 vaccines provided modest protection (26.0%-36.6% of vaccine efficacy) with no serious adverse effects [<xref rid="B129" ref-type="bibr">129</xref>
].</p>
<p>A recent landmark finding that set the standards for immunological protection against malaria infection was established by immunization with irradiated SPZ [<xref rid="B130" ref-type="bibr">130</xref>
<xref rid="B131" ref-type="bibr">131</xref>
]. Because the parasite undergoes morphological changes and displays antigenic variation at each stage of infection, whole parasite vaccines have an advantage [<xref rid="B132" ref-type="bibr">132</xref>
<xref rid="B133" ref-type="bibr">133</xref>
<xref rid="B134" ref-type="bibr">134</xref>
]. In the early 1940s, Russell and Mohan [<xref rid="B130" ref-type="bibr">130</xref>
] first demonstrated that inactivated <italic>P. gallinaceum</italic>
SPZ provided protection against challenge with infectious <italic>P. gallinaceum</italic>
. In 1967, Nussenzweig et al. [<xref rid="B131" ref-type="bibr">131</xref>
] reported that a killed <italic>P. berghei</italic>
SPZ vaccine was unsuccessful, but that an X-ray irradiated SPZ vaccine provided significant protection in an SPZ-challenge mouse model.</p>
<p>In the 1970s, researchers showed that immunizing human volunteers with bites from irradiated mosquitoes carrying <italic>P. falciparum</italic>
SPZ (PfSPZ) or <italic>P. vivax</italic>
SPZ (PvSPZ) provided protection against challenges with infectious SPZ [<xref rid="B135" ref-type="bibr">135</xref>
<xref rid="B136" ref-type="bibr">136</xref>
<xref rid="B137" ref-type="bibr">137</xref>
<xref rid="B138" ref-type="bibr">138</xref>
<xref rid="B139" ref-type="bibr">139</xref>
]. Because infected mosquitoes cannot be used for immunizing large numbers of individuals, a team at the Vaccine Research Center (VRC) of the National Institutes of Health (NIH) and Sanaria Inc. (Rockville, MD, USA), developed an injectable and cryopreserved irradiated PfSPZ vaccine that met the vaccine regulatory standards [<xref rid="B18" ref-type="bibr">18</xref>
]. Sanaria Inc. succeeded in raising mosquitoes on an industrial scale to good manufacturing practice (GMP) levels and harvested large amounts of PfSPZ from the mosquito salivary glands. In the phase 1 clinical trials of irradiated PfSPZ (ClinicalTrials.gov Identifier: NCT01001650), all of the subjects administered five or six doses intravenously showed complete resistance to challenges by bites from infected mosquitoes at 3 weeks after their final immunization, whereas five of six unvaccinated controls developed malaria [<xref rid="B136" ref-type="bibr">136</xref>
<xref rid="B139" ref-type="bibr">139</xref>
]. Additional clinical trials of intravenous administration of the PfSPZ vaccine are planned in multiple locations (ClinicalTrials.gov Identifier: NCT02132299, NCT02215707, NCT0215091, NCT02115 516, NCT02418962).</p>
</sec>
<sec><title>Irradiated Cancer Cell-Based Vaccine Therapy</title>
<p>Cancer, which is a major health concern worldwide, is a leading cause of morbidity and mortality in developed and developing countries. There were ~14 million new cases and 8.2 million cancer deaths in 2012 [<xref rid="B140" ref-type="bibr">140</xref>
]. Currently, traditional therapeutic treatments for cancer control and cure include radiotherapy and chemotherapy, which are commonly used worldwide and are considered the most effective ways to prevent tumor growth [<xref rid="B3" ref-type="bibr">3</xref>
<xref rid="B141" ref-type="bibr">141</xref>
<xref rid="B142" ref-type="bibr">142</xref>
]. Chemotherapy targets the cells that grow and divide quickly, one of the major properties of tumor cells, but causes serious adverse effects as it also targets healthy, fast-dividing cells, such as blood cells and those lining the mouth, stomach, intestines and hair follicles. Hence, myelosuppression (decreased production of blood cells), mucositis (inflammation of the lining of the digestive tract), and alopecia (hair loss) commonly occur after chemotherapy [<xref rid="B143" ref-type="bibr">143</xref>
<xref rid="B144" ref-type="bibr">144</xref>
<xref rid="B145" ref-type="bibr">145</xref>
<xref rid="B146" ref-type="bibr">146</xref>
<xref rid="B147" ref-type="bibr">147</xref>
]. Radiation therapy using ionizing radiation works by damaging the DNA of tumor cells, leading to cell death. Compared to surgery, radiotherapy is less painful, but the severity and longevity of side effects depend on the dose and duration of radiation administered. The symptoms vary from patient to patient and depend on the concurrent treatment, such as chemotherapy. Common acute side effects include nausea, vomiting, epithelial damage, stomach sores, intestinal discomfort and even infertility [<xref rid="B148" ref-type="bibr">148</xref>
<xref rid="B149" ref-type="bibr">149</xref>
<xref rid="B150" ref-type="bibr">150</xref>
]. The side effects are caused by damage to the blood vessels and connective tissues, which can lead to fibrosis, lymphedema, and heart disease, which represent hidden future threats. Thus, new and better prophylactic treatments are needed.</p>
<p>A recently developed therapeutic treatment in cancer prevention is a cancer vaccine. Numerous different kinds of cancer vaccines have been tested in clinical trials, but the clinical benefits for the majority of cancer patients still need to be evaluated and confirmed. Cancer vaccines are designed to prevent or cure cancers using the patient's own whole tumor cells or part of the tumor-specific cancer antigens as the source of the vaccines. Unlike chemotherapies and radiotherapies, these vaccines would not cause serious side effects, which would offer an alternative treatment for patients in cases where traditional treatments are not effective. Furthermore, the combination of a cancer vaccine with other cancer therapies could enhance the efficacy of any treatment.</p>
<p>Cancer treatment vaccines are made with the patient's own blood dendrite cells stimulated with cancer antigen(s). These can effectively inhibit or stop tumor cell growth and prevent re-occurrence of cancer after chemotherapy and radiotherapy [<xref rid="B151" ref-type="bibr">151</xref>
]. In 2010, the Food and Drug Administration (FDA) approved the first cancer treatment vaccine, Provenge (Dendreon, Seattle, WA, USA), which is a patient-customized vaccine targeting metastatic prostate cancer [<xref rid="B152" ref-type="bibr">152</xref>
]. This vaccine is made from cultured dendritic cells taken from the patient and stimulated with prostatic acid phosphatase (PAP) antigen with granulocyte-macrophage colony-stimulating factor (GM-CSF). Re-infusion of the stimulated dendritic cells into the patient effectively stimulates T-cell dependent immunity, which kills the tumor cells expressing PAP [<xref rid="B153" ref-type="bibr">153</xref>
]. Results from a clinical trial showed that Provenge reduced the risk of death by 22% and increased survival by 4.1 months compared to the placebo group [<xref rid="B154" ref-type="bibr">154</xref>
]. However, the cost of current patient-customized therapeutic cancer vaccines is extremely high and the time interval of treatment is long. Both these factors will prevent the vaccine from being widely used worldwide. Provenge treatment consists of three infusions at ~two-week intervals for one month, and the cost for a complete course of treatment is $93,000 [<xref rid="B140" ref-type="bibr">140</xref>
]. Because of these limitations, new types of cell-based cancer vaccines are being developed.</p>
<p>One of most promising therapeutic cell-based cancer vaccines is GVAX (GM-CSF gene-transduced irradiated cancer vaccine cells) which is one of the vaccines furthest along the process in pre-clinical and clinical trials [<xref rid="B155" ref-type="bibr">155</xref>
]. Unlike patient-specific cancer vaccines, this vaccine has been developed using patient-specific cancer cells genetically modified to secrete GM-CSF. This makes it easy to manufacture vaccines for various tumor types, such as melanoma, renal, lung, prostate, and pancreatic tumors [<xref rid="B156" ref-type="bibr">156</xref>
]. Irradiated tumor cells can involve the apoptotic bodies, which would be accepted by the dendritic cells. When the dendritic cells interact with the antigens expressed by irradiated tumor cells, they become mature and present the antigens. In addition, allogenic tumor cell secreting recombinant GM-CSF chemotactically attract immature dendritic cells to induce maturation. The dendritic cells presenting the antigen expressed by the irradiated tumor cells then activate CD4 and CD8 lymphocytes directly [<xref rid="B157" ref-type="bibr">157</xref>
]. To date, there are many types of GVAX vaccine in clinical trials, either alone or in combination with other therapies, to improve treatment options (<xref ref-type="table" rid="T2">Table 2</xref>
). For example, a GVAX vaccine for prostate cancer (GVAX-PCa) with a co-treatment of Ipilimumab, which is a humanized monoclonal antibody and functions as a CTLA-4 blocker, was first approved by the FDA for the treatment of advanced melanoma in 2011 [<xref rid="B158" ref-type="bibr">158</xref>
]. Clinically, GVAX immunotherapy combined with Ipilimumab leads to the development of specific antibodies against the tumor cells which prolonged patient survival in cases of pancreatic and prostate cancers in clinical trials (ClinicalTrials.gov Identifier: NCT00836407 and NCT01510288) [<xref rid="B25" ref-type="bibr">25</xref>
].</p>
</sec>
<sec sec-type="conclusions"><title>Conclusion</title>
<p>Gamma radiation is not a new technique, and has been extensively utilized in the past to sterilize foods and create inactivated vaccines. Whether gamma radiation is superior to conventional inactivation methods, such as heat and chemical treatments, remains a controversial issue. However, due to its ability to effectively penetrate pathogens and cancer cells and specifically target nucleic acids whilst causing less damage to surface antigenic proteins, demands for the use of gamma radiation are increasing to develop safe and simple vaccines. In addition, gamma radiation has several advantages over the use of inactive forms of vaccines, such as the ability to inactivate large volumes, they can be stored in closed containers, and there is no requirement to remove chemical compounds after inactivation. Despite these advantages, no irradiated vaccines have been licensed to date. Here, we reviewed and summarized the current situation regarding irradiated vaccines in pre-clinical and clinical studies. Some irradiated vaccines showed no surprising results compared to live attenuated- or chemically inactivated vaccines, but most of the pre-clinical studies suggested that irradiated vaccines provide more potential immunogenicity than other inactivation methods. Moreover, the metabolically active form of irradiated vaccines were able to activate cytotoxic T cells, which are important immune cells for treating intracellular pathogens and cancers. Therefore, radiation inactivation might provide a feasible, broad-spectrum, simple, and effective technique for the development of novel vaccines.</p>
</sec>
</body>
<back><fn-group><fn fn-type="conflict"><p>No potential conflict of interest relevant to this article was reported.</p>
</fn>
</fn-group>
<ref-list><ref id="B1"><label>1</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>DeLaney</surname>
<given-names>TF</given-names>
</name>
<name><surname>Trofimov</surname>
<given-names>AV</given-names>
</name>
<name><surname>Engelsman</surname>
<given-names>M</given-names>
</name>
<name><surname>Suit</surname>
<given-names>HD</given-names>
</name>
</person-group>
<article-title>Advanced-technology radiation therapy in the management of bone and soft tissue sarcomas</article-title>
<source>Cancer Control</source>
<year>2005</year>
<volume>12</volume>
<fpage>27</fpage>
<lpage>35</lpage>
<pub-id pub-id-type="pmid">15668650</pub-id>
</element-citation>
</ref>
<ref id="B2"><label>2</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barker</surname>
<given-names>CA</given-names>
</name>
<name><surname>Postow</surname>
<given-names>MA</given-names>
</name>
</person-group>
<article-title>Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes</article-title>
<source>Int J Radiat Oncol Biol Phys</source>
<year>2014</year>
<volume>88</volume>
<fpage>986</fpage>
<lpage>997</lpage>
<pub-id pub-id-type="pmid">24661650</pub-id>
</element-citation>
</ref>
<ref id="B3"><label>3</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amin</surname>
<given-names>NP</given-names>
</name>
<name><surname>Sher</surname>
<given-names>DJ</given-names>
</name>
<name><surname>Konski</surname>
<given-names>AA</given-names>
</name>
</person-group>
<article-title>Systematic review of the cost effectiveness of radiation therapy for prostate cancer from 2003 to 2013</article-title>
<source>Appl Health Econ Health Policy</source>
<year>2014</year>
<volume>12</volume>
<fpage>391</fpage>
<lpage>408</lpage>
<pub-id pub-id-type="pmid">25022451</pub-id>
</element-citation>
</ref>
<ref id="B4"><label>4</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McDonald</surname>
<given-names>JC</given-names>
</name>
</person-group>
<article-title>Industrial radiation processing: working behind the scenes</article-title>
<source>Radiat Prot Dosimetry</source>
<year>2004</year>
<volume>109</volume>
<fpage>173</fpage>
<lpage>174</lpage>
<pub-id pub-id-type="pmid">15254319</pub-id>
</element-citation>
</ref>
<ref id="B5"><label>5</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Musilek</surname>
<given-names>L</given-names>
</name>
</person-group>
<article-title>Applied Radiation and Isotopes. The 7th International Topical Meeting on Industrial Radiation and Radio isotope Measurement Application (IRRMA-7). Foreword</article-title>
<source>Appl Radiat Isot</source>
<year>2010</year>
<volume>68</volume>
<fpage>517</fpage>
<pub-id pub-id-type="pmid">20129795</pub-id>
</element-citation>
</ref>
<ref id="B6"><label>6</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Awan</surname>
<given-names>MS</given-names>
</name>
<name><surname>Tabbasam</surname>
<given-names>N</given-names>
</name>
<name><surname>Ayub</surname>
<given-names>N</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Gamma radiation induced mutagenesis in Aspergillus niger to enhance its microbial fermentation activity for industrial enzyme production</article-title>
<source>Mol Biol Rep</source>
<year>2011</year>
<volume>38</volume>
<fpage>1367</fpage>
<lpage>1374</lpage>
<pub-id pub-id-type="pmid">20632114</pub-id>
</element-citation>
</ref>
<ref id="B7"><label>7</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Galante</surname>
<given-names>AM</given-names>
</name>
<name><surname>Campos</surname>
<given-names>LL</given-names>
</name>
</person-group>
<article-title>Mapping radiation fields in containers for industrial gamma-irradiation using polycarbonate dosimeters</article-title>
<source>Appl Radiat Isot</source>
<year>2012</year>
<volume>70</volume>
<fpage>1264</fpage>
<lpage>1266</lpage>
<pub-id pub-id-type="pmid">22264796</pub-id>
</element-citation>
</ref>
<ref id="B8"><label>8</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Choi</surname>
<given-names>JI</given-names>
</name>
<name><surname>Yoon</surname>
<given-names>M</given-names>
</name>
<name><surname>Joe</surname>
<given-names>M</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Development of microalga Scenedesmus dimorphus mutant with higher lipid content by radiation breeding</article-title>
<source>Bioprocess Biosyst Eng</source>
<year>2014</year>
<volume>37</volume>
<fpage>2437</fpage>
<lpage>2444</lpage>
<pub-id pub-id-type="pmid">24871276</pub-id>
</element-citation>
</ref>
<ref id="B9"><label>9</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sugimoto</surname>
<given-names>T</given-names>
</name>
<name><surname>Shinozaki</surname>
<given-names>T</given-names>
</name>
<name><surname>Naruse</surname>
<given-names>T</given-names>
</name>
<name><surname>Miyamoto</surname>
<given-names>Y</given-names>
</name>
</person-group>
<article-title>Who was concerned about radiation, food safety, and natural disasters after the great East Japan earthquake and Fukushima catastrophe? A nationwide cross-sectional survey in 2012</article-title>
<source>PLoS One</source>
<year>2014</year>
<volume>9</volume>
<fpage>e106377</fpage>
<pub-id pub-id-type="pmid">25181292</pub-id>
</element-citation>
</ref>
<ref id="B10"><label>10</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cho</surname>
<given-names>HW</given-names>
</name>
<name><surname>Howard</surname>
<given-names>CR</given-names>
</name>
<name><surname>Lee</surname>
<given-names>HW</given-names>
</name>
</person-group>
<article-title>Review of an inactivated vaccine against hantaviruses</article-title>
<source>Intervirology</source>
<year>2002</year>
<volume>45</volume>
<fpage>328</fpage>
<lpage>333</lpage>
<pub-id pub-id-type="pmid">12602351</pub-id>
</element-citation>
</ref>
<ref id="B11"><label>11</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McKeage</surname>
<given-names>K</given-names>
</name>
</person-group>
<article-title>Inactivated quadrivalent split-virus seasonal influenza vaccine (Fluarix(R) quadrivalent): a review of its use in the prevention of disease caused by influenza A and B</article-title>
<source>Drugs</source>
<year>2013</year>
<volume>73</volume>
<fpage>1587</fpage>
<lpage>1594</lpage>
<pub-id pub-id-type="pmid">24022123</pub-id>
</element-citation>
</ref>
<ref id="B12"><label>12</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Grassly</surname>
<given-names>NC</given-names>
</name>
</person-group>
<article-title>Immunogenicity and effectiveness of routine immunization with 1 or 2 doses of inactivated poliovirus vaccine: systematic review and meta-analysis</article-title>
<source>J Infect Dis</source>
<year>2014</year>
<volume>210</volume>
<issue>Suppl 1</issue>
<fpage>S439</fpage>
<lpage>S446</lpage>
<pub-id pub-id-type="pmid">24634499</pub-id>
</element-citation>
</ref>
<ref id="B13"><label>13</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gasparini</surname>
<given-names>R</given-names>
</name>
<name><surname>Amicizia</surname>
<given-names>D</given-names>
</name>
<name><surname>Lai</surname>
<given-names>PL</given-names>
</name>
<name><surname>Panatto</surname>
<given-names>D</given-names>
</name>
</person-group>
<article-title>Live attenuated influenza vaccine: a review</article-title>
<source>J Prev Med Hyg</source>
<year>2011</year>
<volume>52</volume>
<fpage>95</fpage>
<lpage>101</lpage>
<pub-id pub-id-type="pmid">22010534</pub-id>
</element-citation>
</ref>
<ref id="B14"><label>14</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mayr</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>Historical review of smallpox, the eradication of smallpox and the attenuated smallpox MVA vaccine</article-title>
<source>Berl Munch Tierarztl Wochenschr</source>
<year>1999</year>
<volume>112</volume>
<fpage>322</fpage>
<lpage>328</lpage>
<pub-id pub-id-type="pmid">10507180</pub-id>
</element-citation>
</ref>
<ref id="B15"><label>15</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thomas</surname>
<given-names>TN</given-names>
</name>
<name><surname>Reef</surname>
<given-names>S</given-names>
</name>
<name><surname>Neff</surname>
<given-names>L</given-names>
</name>
<name><surname>Sniadack</surname>
<given-names>MM</given-names>
</name>
<name><surname>Mootrey</surname>
<given-names>GT</given-names>
</name>
</person-group>
<article-title>A review of the smallpox vaccine adverse events active surveillance system</article-title>
<source>Clin Infect Dis</source>
<year>2008</year>
<volume>46</volume>
<issue>Suppl 3</issue>
<fpage>S212</fpage>
<lpage>S220</lpage>
<pub-id pub-id-type="pmid">18284361</pub-id>
</element-citation>
</ref>
<ref id="B16"><label>16</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brown</surname>
<given-names>CC</given-names>
</name>
</person-group>
<article-title>A review of three pathology-based techniques for retrospective diagnosis of rinderpest, with comparison to virus isolation</article-title>
<source>Res Vet Sci</source>
<year>1997</year>
<volume>63</volume>
<fpage>103</fpage>
<lpage>106</lpage>
<pub-id pub-id-type="pmid">9429240</pub-id>
</element-citation>
</ref>
<ref id="B17"><label>17</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Njeumi</surname>
<given-names>F</given-names>
</name>
<name><surname>Taylor</surname>
<given-names>W</given-names>
</name>
<name><surname>Diallo</surname>
<given-names>A</given-names>
</name>
<etal></etal>
</person-group>
<article-title>The long journey: a brief review of the eradication of rinderpest</article-title>
<source>Rev Sci Tech</source>
<year>2012</year>
<volume>31</volume>
<fpage>729</fpage>
<lpage>746</lpage>
<pub-id pub-id-type="pmid">23520729</pub-id>
</element-citation>
</ref>
<ref id="B18"><label>18</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Luke</surname>
<given-names>TC</given-names>
</name>
<name><surname>Hoffman</surname>
<given-names>SL</given-names>
</name>
</person-group>
<article-title>Rationale and plans for developing a non-replicating, metabolically active, radiation-attenuated Plasmodium falciparum sporozoite vaccine</article-title>
<source>J Exp Biol</source>
<year>2003</year>
<volume>206</volume>
<fpage>3803</fpage>
<lpage>3808</lpage>
<pub-id pub-id-type="pmid">14506215</pub-id>
</element-citation>
</ref>
<ref id="B19"><label>19</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hewitson</surname>
<given-names>JP</given-names>
</name>
<name><surname>Hamblin</surname>
<given-names>PA</given-names>
</name>
<name><surname>Mountford</surname>
<given-names>AP</given-names>
</name>
</person-group>
<article-title>Immunity induced by the radiation-attenuated schistosome vaccine</article-title>
<source>Parasite Immunol</source>
<year>2005</year>
<volume>27</volume>
<fpage>271</fpage>
<lpage>280</lpage>
<pub-id pub-id-type="pmid">16138848</pub-id>
</element-citation>
</ref>
<ref id="B20"><label>20</label>
<element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Plotkin</surname>
<given-names>SA</given-names>
</name>
</person-group>
<source>History of vaccine development</source>
<publisher-loc>New York</publisher-loc>
<publisher-name>Springer</publisher-name>
<year>2011</year>
</element-citation>
</ref>
<ref id="B21"><label>21</label>
<element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Artenstein</surname>
<given-names>AW</given-names>
</name>
</person-group>
<source>Vaccines: a biography</source>
<publisher-loc>New York</publisher-loc>
<publisher-name>Springer</publisher-name>
<year>2010</year>
</element-citation>
</ref>
<ref id="B22"><label>22</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arama</surname>
<given-names>C</given-names>
</name>
<name><surname>Troye-Blomberg</surname>
<given-names>M</given-names>
</name>
</person-group>
<article-title>The path of malaria vaccine development: challenges and perspectives</article-title>
<source>J Intern Med</source>
<year>2014</year>
<volume>275</volume>
<fpage>456</fpage>
<lpage>466</lpage>
<pub-id pub-id-type="pmid">24635625</pub-id>
</element-citation>
</ref>
<ref id="B23"><label>23</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jindal</surname>
<given-names>H</given-names>
</name>
<name><surname>Bhatt</surname>
<given-names>B</given-names>
</name>
<name><surname>Malik</surname>
<given-names>JS</given-names>
</name>
<name><surname>Sk</surname>
<given-names>S</given-names>
</name>
<name><surname>Mehta</surname>
<given-names>B</given-names>
</name>
</person-group>
<article-title>Malaria vaccine: a step toward elimination</article-title>
<source>Hum Vaccin Immunother</source>
<year>2014</year>
<volume>10</volume>
<fpage>1752</fpage>
<lpage>1754</lpage>
<pub-id pub-id-type="pmid">24643280</pub-id>
</element-citation>
</ref>
<ref id="B24"><label>24</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Qin</surname>
<given-names>L</given-names>
</name>
<name><surname>Smith</surname>
<given-names>BD</given-names>
</name>
<name><surname>Tsai</surname>
<given-names>HL</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Induction of high-titer IgG antibodies against multiple leukemia-associated antigens in CML patients with clinical responses to K562/GVAX immunotherapy</article-title>
<source>Blood Cancer J</source>
<year>2013</year>
<volume>3</volume>
<fpage>e145</fpage>
<pub-id pub-id-type="pmid">24013666</pub-id>
</element-citation>
</ref>
<ref id="B25"><label>25</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>De Remigis</surname>
<given-names>A</given-names>
</name>
<name><surname>de Gruijl</surname>
<given-names>TD</given-names>
</name>
<name><surname>Uram</surname>
<given-names>JN</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Development of thyroglobulin antibodies after GVAX immunotherapy is associated with prolonged survival</article-title>
<source>Int J Cancer</source>
<year>2015</year>
<volume>136</volume>
<fpage>127</fpage>
<lpage>137</lpage>
<pub-id pub-id-type="pmid">24832153</pub-id>
</element-citation>
</ref>
<ref id="B26"><label>26</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Le</surname>
<given-names>DT</given-names>
</name>
<name><surname>Wang-Gillam</surname>
<given-names>A</given-names>
</name>
<name><surname>Picozzi</surname>
<given-names>V</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer</article-title>
<source>J Clin Oncol</source>
<year>2015</year>
<volume>33</volume>
<fpage>1325</fpage>
<lpage>1333</lpage>
<pub-id pub-id-type="pmid">25584002</pub-id>
</element-citation>
</ref>
<ref id="B27"><label>27</label>
<element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Rappuoli</surname>
<given-names>R</given-names>
</name>
<name><surname>Bagnoli</surname>
<given-names>F</given-names>
</name>
</person-group>
<source>Vaccine design: innovative approaches and novel strategies</source>
<publisher-loc>Norfolk</publisher-loc>
<publisher-name>Caister Academic Press</publisher-name>
<year>2011</year>
</element-citation>
</ref>
<ref id="B28"><label>28</label>
<element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Plotkin</surname>
<given-names>SA</given-names>
</name>
<name><surname>Orenstein</surname>
<given-names>WA</given-names>
</name>
<name><surname>Offit</surname>
<given-names>PA</given-names>
</name>
</person-group>
<source>Vaccines</source>
<publisher-loc>Philadelphia, PA</publisher-loc>
<publisher-name>Elsevier</publisher-name>
<year>2008</year>
</element-citation>
</ref>
<ref id="B29"><label>29</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Madsen</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title>Vaccination against whooping cough</article-title>
<source>JAMA</source>
<year>1933</year>
<volume>101</volume>
<fpage>187</fpage>
<lpage>188</lpage>
</element-citation>
</ref>
<ref id="B30"><label>30</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brown</surname>
<given-names>F</given-names>
</name>
</person-group>
<article-title>Review of accidents caused by incomplete inactivation of viruses</article-title>
<source>Dev Biol Stand</source>
<year>1993</year>
<volume>81</volume>
<fpage>103</fpage>
<lpage>107</lpage>
<pub-id pub-id-type="pmid">8174792</pub-id>
</element-citation>
</ref>
<ref id="B31"><label>31</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Perrin</surname>
<given-names>P</given-names>
</name>
<name><surname>Morgeaux</surname>
<given-names>S</given-names>
</name>
</person-group>
<article-title>Inactivation of DNA by beta-propiolactone</article-title>
<source>Biologicals</source>
<year>1995</year>
<volume>23</volume>
<fpage>207</fpage>
<lpage>211</lpage>
<pub-id pub-id-type="pmid">8527119</pub-id>
</element-citation>
</ref>
<ref id="B32"><label>32</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Uittenbogaard</surname>
<given-names>JP</given-names>
</name>
<name><surname>Zomer</surname>
<given-names>B</given-names>
</name>
<name><surname>Hoogerhout</surname>
<given-names>P</given-names>
</name>
<name><surname>Metz</surname>
<given-names>B</given-names>
</name>
</person-group>
<article-title>Reactions of beta-propiolactone with nucleobase analogues, nucleosides, and peptides: implications for the inactivation of viruses</article-title>
<source>J Biol Chem</source>
<year>2011</year>
<volume>286</volume>
<fpage>36198</fpage>
<lpage>36214</lpage>
<pub-id pub-id-type="pmid">21868382</pub-id>
</element-citation>
</ref>
<ref id="B33"><label>33</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Swanson</surname>
<given-names>MC</given-names>
</name>
<name><surname>Rosanoff</surname>
<given-names>E</given-names>
</name>
<name><surname>Gurwith</surname>
<given-names>M</given-names>
</name>
<name><surname>Deitch</surname>
<given-names>M</given-names>
</name>
<name><surname>Schnurrenberger</surname>
<given-names>P</given-names>
</name>
<name><surname>Reed</surname>
<given-names>CE</given-names>
</name>
</person-group>
<article-title>IgE and IgG antibodies to beta-propiolactone and human serum albumin associated with urticarial reactions to rabies vaccine</article-title>
<source>J Infect Dis</source>
<year>1987</year>
<volume>155</volume>
<fpage>909</fpage>
<lpage>913</lpage>
<pub-id pub-id-type="pmid">3559291</pub-id>
</element-citation>
</ref>
<ref id="B34"><label>34</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stauffer</surname>
<given-names>AO</given-names>
</name>
<name><surname>Barbosa</surname>
<given-names>VC</given-names>
</name>
</person-group>
<article-title>Dissemination strategy for immunizing scale-free networks</article-title>
<source>Phys Rev E Stat Nonlin Soft Matter Phys</source>
<year>2006</year>
<volume>74</volume>
<fpage>056105</fpage>
<pub-id pub-id-type="pmid">17279966</pub-id>
</element-citation>
</ref>
<ref id="B35"><label>35</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Horl</surname>
<given-names>WH</given-names>
</name>
<name><surname>Riegel</surname>
<given-names>W</given-names>
</name>
<name><surname>Schollmeyer</surname>
<given-names>P</given-names>
</name>
</person-group>
<article-title>Effect of gamma radiation versus ethylene oxide sterilization of dialyzers and blood lines on plasma levels of granulocyte elastase in hemodialyzed patients</article-title>
<source>Clin Nephrol</source>
<year>1985</year>
<volume>24</volume>
<fpage>232</fpage>
<lpage>236</lpage>
<pub-id pub-id-type="pmid">3852707</pub-id>
</element-citation>
</ref>
<ref id="B36"><label>36</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dean</surname>
<given-names>EE</given-names>
</name>
<name><surname>Howie</surname>
<given-names>DL</given-names>
</name>
</person-group>
<article-title>Safety of food sterilization by ionizing radiation</article-title>
<source>Bull Parenter Drug Assoc</source>
<year>1964</year>
<volume>18</volume>
<fpage>12</fpage>
<lpage>26</lpage>
<pub-id pub-id-type="pmid">14169958</pub-id>
</element-citation>
</ref>
<ref id="B37"><label>37</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goldblith</surname>
<given-names>SA</given-names>
</name>
</person-group>
<article-title>Radiation sterilization of food</article-title>
<source>Nature</source>
<year>1966</year>
<volume>210</volume>
<fpage>433</fpage>
<lpage>434</lpage>
<pub-id pub-id-type="pmid">5963249</pub-id>
</element-citation>
</ref>
<ref id="B38"><label>38</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Datta</surname>
<given-names>M</given-names>
</name>
</person-group>
<article-title>The 5 component acellular pertussis vaccine combined with tetanus and diphtheria toxoids was efficacious in adolescents and adults</article-title>
<source>Evid Based Med</source>
<year>2006</year>
<volume>11</volume>
<fpage>51</fpage>
<pub-id pub-id-type="pmid">17213081</pub-id>
</element-citation>
</ref>
<ref id="B39"><label>39</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Datta</surname>
<given-names>SK</given-names>
</name>
<name><surname>Okamoto</surname>
<given-names>S</given-names>
</name>
<name><surname>Hayashi</surname>
<given-names>T</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Vaccination with irradiated Listeria induces protective T cell immunity</article-title>
<source>Immunity</source>
<year>2006</year>
<volume>25</volume>
<fpage>143</fpage>
<lpage>152</lpage>
<pub-id pub-id-type="pmid">16860763</pub-id>
</element-citation>
</ref>
<ref id="B40"><label>40</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Magnani</surname>
<given-names>DM</given-names>
</name>
<name><surname>Harms</surname>
<given-names>JS</given-names>
</name>
<name><surname>Durward</surname>
<given-names>MA</given-names>
</name>
<name><surname>Splitter</surname>
<given-names>GA</given-names>
</name>
</person-group>
<article-title>Nondividing but metabolically active gamma-irradiated Brucella melitensis is protective against virulent B. melitensis challenge in mice</article-title>
<source>Infect Immun</source>
<year>2009</year>
<volume>77</volume>
<fpage>5181</fpage>
<lpage>5189</lpage>
<pub-id pub-id-type="pmid">19703982</pub-id>
</element-citation>
</ref>
<ref id="B41"><label>41</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Quach</surname>
<given-names>C</given-names>
</name>
</person-group>
<article-title>Vaccinating high-risk children with the intranasal live-attenuated influenza vaccine: the Quebec experience</article-title>
<source>Paediatr Respir Rev</source>
<year>2014</year>
<volume>15</volume>
<fpage>340</fpage>
<lpage>347</lpage>
<pub-id pub-id-type="pmid">25242731</pub-id>
</element-citation>
</ref>
<ref id="B42"><label>42</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wutzler</surname>
<given-names>P</given-names>
</name>
<name><surname>Hardt</surname>
<given-names>R</given-names>
</name>
<name><surname>Knuf</surname>
<given-names>M</given-names>
</name>
<name><surname>Wahle</surname>
<given-names>K</given-names>
</name>
</person-group>
<article-title>Targeted vaccine selection in influenza vaccination</article-title>
<source>Dtsch Arztebl Int</source>
<year>2013</year>
<volume>110</volume>
<fpage>793</fpage>
<lpage>798</lpage>
<pub-id pub-id-type="pmid">24314622</pub-id>
</element-citation>
</ref>
<ref id="B43"><label>43</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pica</surname>
<given-names>N</given-names>
</name>
<name><surname>Palese</surname>
<given-names>P</given-names>
</name>
</person-group>
<article-title>Toward a universal influenza virus vaccine: prospects and challenges</article-title>
<source>Annu Rev Med</source>
<year>2013</year>
<volume>64</volume>
<fpage>189</fpage>
<lpage>202</lpage>
<pub-id pub-id-type="pmid">23327522</pub-id>
</element-citation>
</ref>
<ref id="B44"><label>44</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Johnston</surname>
<given-names>JA</given-names>
</name>
<name><surname>Tincher</surname>
<given-names>LB</given-names>
</name>
<name><surname>Lowe</surname>
<given-names>DK</given-names>
</name>
</person-group>
<article-title>Booster and higher antigen doses of inactivated influenza vaccine in HIV-infected patients</article-title>
<source>Ann Pharmacother</source>
<year>2013</year>
<volume>47</volume>
<fpage>1712</fpage>
<lpage>1716</lpage>
<pub-id pub-id-type="pmid">24259616</pub-id>
</element-citation>
</ref>
<ref id="B45"><label>45</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Haber</surname>
<given-names>P</given-names>
</name>
<name><surname>Moro</surname>
<given-names>PL</given-names>
</name>
<name><surname>McNeil</surname>
<given-names>MM</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Post-licensure surveillance of trivalent live attenuated influenza vaccine in adults, United States, Vaccine Adverse Event Reporting System (VAERS), July 2005-June 2013</article-title>
<source>Vaccine</source>
<year>2014</year>
<volume>32</volume>
<fpage>6499</fpage>
<lpage>6504</lpage>
<pub-id pub-id-type="pmid">25258101</pub-id>
</element-citation>
</ref>
<ref id="B46"><label>46</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Prutsky</surname>
<given-names>GJ</given-names>
</name>
<name><surname>Domecq</surname>
<given-names>JP</given-names>
</name>
<name><surname>Elraiyah</surname>
<given-names>T</given-names>
</name>
<name><surname>Prokop</surname>
<given-names>LJ</given-names>
</name>
<name><surname>Murad</surname>
<given-names>MH</given-names>
</name>
</person-group>
<article-title>Assessing the evidence: live attenuated influenza vaccine in children younger than 2 years: a systematic review</article-title>
<source>Pediatr Infect Dis J</source>
<year>2014</year>
<volume>33</volume>
<fpage>e106</fpage>
<lpage>e115</lpage>
<pub-id pub-id-type="pmid">24632668</pub-id>
</element-citation>
</ref>
<ref id="B47"><label>47</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jefferson</surname>
<given-names>T</given-names>
</name>
<name><surname>Di Pietrantonj</surname>
<given-names>C</given-names>
</name>
<name><surname>Al-Ansary</surname>
<given-names>LA</given-names>
</name>
<name><surname>Ferroni</surname>
<given-names>E</given-names>
</name>
<name><surname>Thorning</surname>
<given-names>S</given-names>
</name>
<name><surname>Thomas</surname>
<given-names>RE</given-names>
</name>
</person-group>
<article-title>Vaccines for preventing influenza in the elderly</article-title>
<source>Cochrane Database Syst Rev</source>
<year>2010</year>
<issue>2</issue>
<fpage>CD004876</fpage>
<pub-id pub-id-type="pmid">20166072</pub-id>
</element-citation>
</ref>
<ref id="B48"><label>48</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jefferson</surname>
<given-names>T</given-names>
</name>
<name><surname>Rivetti</surname>
<given-names>A</given-names>
</name>
<name><surname>Di Pietrantonj</surname>
<given-names>C</given-names>
</name>
<name><surname>Demicheli</surname>
<given-names>V</given-names>
</name>
<name><surname>Ferroni</surname>
<given-names>E</given-names>
</name>
</person-group>
<article-title>Vaccines for preventing influenza in healthy children</article-title>
<source>Cochrane Database Syst Rev</source>
<year>2012</year>
<volume>8</volume>
<fpage>CD004879</fpage>
<pub-id pub-id-type="pmid">22895945</pub-id>
</element-citation>
</ref>
<ref id="B49"><label>49</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Govaert</surname>
<given-names>TM</given-names>
</name>
<name><surname>Thijs</surname>
<given-names>CT</given-names>
</name>
<name><surname>Masurel</surname>
<given-names>N</given-names>
</name>
<name><surname>Sprenger</surname>
<given-names>MJ</given-names>
</name>
<name><surname>Dinant</surname>
<given-names>GJ</given-names>
</name>
<name><surname>Knottnerus</surname>
<given-names>JA</given-names>
</name>
</person-group>
<article-title>The efficacy of influenza vaccination in elderly individuals: a randomized double-blind placebo-controlled trial</article-title>
<source>JAMA</source>
<year>1994</year>
<volume>272</volume>
<fpage>1661</fpage>
<lpage>1665</lpage>
<pub-id pub-id-type="pmid">7966893</pub-id>
</element-citation>
</ref>
<ref id="B50"><label>50</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thompson</surname>
<given-names>WW</given-names>
</name>
<name><surname>Shay</surname>
<given-names>DK</given-names>
</name>
<name><surname>Weintraub</surname>
<given-names>E</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Mortality associated with influenza and respiratory syncytial virus in the United States</article-title>
<source>JAMA</source>
<year>2003</year>
<volume>289</volume>
<fpage>179</fpage>
<lpage>186</lpage>
<pub-id pub-id-type="pmid">12517228</pub-id>
</element-citation>
</ref>
<ref id="B51"><label>51</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Warfield</surname>
<given-names>KL</given-names>
</name>
<name><surname>Swenson</surname>
<given-names>DL</given-names>
</name>
<name><surname>Olinger</surname>
<given-names>GG</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Ebola virus inactivation with preservation of antigenic and structural integrity by a photoinducible alkylating agent</article-title>
<source>J Infect Dis</source>
<year>2007</year>
<volume>196</volume>
<issue>Suppl 2</issue>
<fpage>S276</fpage>
<lpage>S283</lpage>
<pub-id pub-id-type="pmid">17940961</pub-id>
</element-citation>
</ref>
<ref id="B52"><label>52</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sharma</surname>
<given-names>A</given-names>
</name>
<name><surname>Gupta</surname>
<given-names>P</given-names>
</name>
<name><surname>Maheshwari</surname>
<given-names>RK</given-names>
</name>
</person-group>
<article-title>Inactivation of Chikungunya virus by 1,5 iodonapthyl azide</article-title>
<source>Virol J</source>
<year>2012</year>
<volume>9</volume>
<fpage>301</fpage>
<pub-id pub-id-type="pmid">23210745</pub-id>
</element-citation>
</ref>
<ref id="B53"><label>53</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nagayama</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>Inactivation of influenza A virus by gentian violet (GV) and GV-dyed cotton cloth, and bactericidal activities of these agents</article-title>
<source>J Infect Chemother</source>
<year>2006</year>
<volume>12</volume>
<fpage>73</fpage>
<lpage>79</lpage>
<pub-id pub-id-type="pmid">16648946</pub-id>
</element-citation>
</ref>
<ref id="B54"><label>54</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kap</surname>
<given-names>M</given-names>
</name>
<name><surname>Arron</surname>
<given-names>GI</given-names>
</name>
<name><surname>Loibner</surname>
<given-names>M</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Inactivation of influenza A virus, adenovirus, and cytomegalovirus with PAXgene tissue fixative and formalin</article-title>
<source>Biopreserv Biobank</source>
<year>2013</year>
<volume>11</volume>
<fpage>229</fpage>
<lpage>234</lpage>
<pub-id pub-id-type="pmid">24845590</pub-id>
</element-citation>
</ref>
<ref id="B55"><label>55</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fedorova</surname>
<given-names>AA</given-names>
</name>
<name><surname>Azzami</surname>
<given-names>K</given-names>
</name>
<name><surname>Ryabchikova</surname>
<given-names>EI</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Inactivation of a non-enveloped RNA virus by artificial ribonucleases: honey bees and acute bee paralysis virus as a new experimental model for in vivo antiviral activity assessment</article-title>
<source>Antiviral Res</source>
<year>2011</year>
<volume>91</volume>
<fpage>267</fpage>
<lpage>277</lpage>
<pub-id pub-id-type="pmid">21722669</pub-id>
</element-citation>
</ref>
<ref id="B56"><label>56</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dumard</surname>
<given-names>CH</given-names>
</name>
<name><surname>Barroso</surname>
<given-names>SP</given-names>
</name>
<name><surname>de Oliveira</surname>
<given-names>GA</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Full inactivation of human influenza virus by high hydrostatic pressure preserves virus structure and membrane fusion while conferring protection to mice against infection</article-title>
<source>PLoS One</source>
<year>2013</year>
<volume>8</volume>
<fpage>e80785</fpage>
<pub-id pub-id-type="pmid">24282553</pub-id>
</element-citation>
</ref>
<ref id="B57"><label>57</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dembinski</surname>
<given-names>JL</given-names>
</name>
<name><surname>Hungnes</surname>
<given-names>O</given-names>
</name>
<name><surname>Hauge</surname>
<given-names>AG</given-names>
</name>
<name><surname>Kristoffersen</surname>
<given-names>AC</given-names>
</name>
<name><surname>Haneberg</surname>
<given-names>B</given-names>
</name>
<name><surname>Mjaaland</surname>
<given-names>S</given-names>
</name>
</person-group>
<article-title>Hydrogen peroxide inactivation of influenza virus preserves antigenic structure and immunogenicity</article-title>
<source>J Virol Methods</source>
<year>2014</year>
<volume>207</volume>
<fpage>232</fpage>
<lpage>237</lpage>
<pub-id pub-id-type="pmid">25025814</pub-id>
</element-citation>
</ref>
<ref id="B58"><label>58</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Belanger</surname>
<given-names>JM</given-names>
</name>
<name><surname>Raviv</surname>
<given-names>Y</given-names>
</name>
<name><surname>Viard</surname>
<given-names>M</given-names>
</name>
<name><surname>de la Cruz</surname>
<given-names>MJ</given-names>
</name>
<name><surname>Nagashima</surname>
<given-names>K</given-names>
</name>
<name><surname>Blumenthal</surname>
<given-names>R</given-names>
</name>
</person-group>
<article-title>Effects of UVA irradiation, aryl azides, and reactive oxygen species on the orthogonal inactivation of the human immunodeficiency virus (HIV-1)</article-title>
<source>Virology</source>
<year>2011</year>
<volume>417</volume>
<fpage>221</fpage>
<lpage>228</lpage>
<pub-id pub-id-type="pmid">21726886</pub-id>
</element-citation>
</ref>
<ref id="B59"><label>59</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ada</surname>
<given-names>G</given-names>
</name>
</person-group>
<article-title>Vaccines and vaccination</article-title>
<source>N Engl J Med</source>
<year>2001</year>
<volume>345</volume>
<fpage>1042</fpage>
<lpage>1053</lpage>
<pub-id pub-id-type="pmid">11586958</pub-id>
</element-citation>
</ref>
<ref id="B60"><label>60</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mullbacher</surname>
<given-names>A</given-names>
</name>
<name><surname>Ada</surname>
<given-names>GL</given-names>
</name>
<name><surname>Hla</surname>
<given-names>RT</given-names>
</name>
</person-group>
<article-title>Gamma-irradiated influenza A virus can prime for a cross-reactive and cross-protective immune response against influenza A viruses</article-title>
<source>Immunol Cell Biol</source>
<year>1988</year>
<volume>66</volume>
<issue>Pt 2</issue>
<fpage>153</fpage>
<lpage>157</lpage>
<pub-id pub-id-type="pmid">2846435</pub-id>
</element-citation>
</ref>
<ref id="B61"><label>61</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mullbacher</surname>
<given-names>A</given-names>
</name>
<name><surname>Marshall</surname>
<given-names>ID</given-names>
</name>
<name><surname>Blanden</surname>
<given-names>RV</given-names>
</name>
</person-group>
<article-title>Cross-reactive cytotoxic T cells to alphavirus infection</article-title>
<source>Scand J Immunol</source>
<year>1979</year>
<volume>10</volume>
<fpage>291</fpage>
<lpage>296</lpage>
<pub-id pub-id-type="pmid">316916</pub-id>
</element-citation>
</ref>
<ref id="B62"><label>62</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mullbacher</surname>
<given-names>A</given-names>
</name>
<name><surname>Marshall</surname>
<given-names>ID</given-names>
</name>
<name><surname>Ferris</surname>
<given-names>P</given-names>
</name>
</person-group>
<article-title>Classification of Barmah Forest virus as an alphavirus using cytotoxic T cell assays</article-title>
<source>J Gen Virol</source>
<year>1986</year>
<volume>67</volume>
<issue>Pt 2</issue>
<fpage>295</fpage>
<lpage>299</lpage>
<pub-id pub-id-type="pmid">3003237</pub-id>
</element-citation>
</ref>
<ref id="B63"><label>63</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alsharifi</surname>
<given-names>M</given-names>
</name>
<name><surname>Mullbacher</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>The gamma-irradiated influenza vaccine and the prospect of producing safe vaccines in general</article-title>
<source>Immunol Cell Biol</source>
<year>2010</year>
<volume>88</volume>
<fpage>103</fpage>
<lpage>104</lpage>
<pub-id pub-id-type="pmid">19859081</pub-id>
</element-citation>
</ref>
<ref id="B64"><label>64</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Putkonen</surname>
<given-names>P</given-names>
</name>
<name><surname>Thorstensson</surname>
<given-names>R</given-names>
</name>
<name><surname>Cranage</surname>
<given-names>M</given-names>
</name>
<etal></etal>
</person-group>
<article-title>A formalin inactivated whole SIVmac vaccine in Ribi adjuvant protects against homologous and heterologous SIV challenge</article-title>
<source>J Med Primatol</source>
<year>1992</year>
<volume>21</volume>
<fpage>108</fpage>
<lpage>112</lpage>
<pub-id pub-id-type="pmid">1433260</pub-id>
</element-citation>
</ref>
<ref id="B65"><label>65</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Murphey-Corb</surname>
<given-names>M</given-names>
</name>
<name><surname>Martin</surname>
<given-names>LN</given-names>
</name>
<name><surname>Davison-Fairburn</surname>
<given-names>B</given-names>
</name>
<etal></etal>
</person-group>
<article-title>A formalin-inactivated whole SIV vaccine confers protection in macaques</article-title>
<source>Science</source>
<year>1989</year>
<volume>246</volume>
<fpage>1293</fpage>
<lpage>1297</lpage>
<pub-id pub-id-type="pmid">2555923</pub-id>
</element-citation>
</ref>
<ref id="B66"><label>66</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Trauger</surname>
<given-names>R</given-names>
</name>
</person-group>
<article-title>Remune response</article-title>
<source>Nat Biotechnol</source>
<year>1998</year>
<volume>16</volume>
<fpage>314</fpage>
<pub-id pub-id-type="pmid">9555714</pub-id>
</element-citation>
</ref>
<ref id="B67"><label>67</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Churdboonchart</surname>
<given-names>V</given-names>
</name>
<name><surname>Sakondhavat</surname>
<given-names>C</given-names>
</name>
<name><surname>Kulpradist</surname>
<given-names>S</given-names>
</name>
<etal></etal>
</person-group>
<article-title>A double-blind, adjuvant-controlled trial of human immunodeficiency virus type 1 (HIV-1) immunogen (Remune) monotherapy in asymptomatic, HIV-1-infected thai subjects with CD4-cell counts of >300</article-title>
<source>Clin Diagn Lab Immunol</source>
<year>2000</year>
<volume>7</volume>
<fpage>728</fpage>
<lpage>733</lpage>
<pub-id pub-id-type="pmid">10973445</pub-id>
</element-citation>
</ref>
<ref id="B68"><label>68</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moss</surname>
<given-names>RB</given-names>
</name>
<name><surname>Giermakowska</surname>
<given-names>W</given-names>
</name>
<name><surname>Lanza</surname>
<given-names>P</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Cross-clade immune responses after immunization with a whole-killed gp120-depleted human immunodeficiency virus type-1 immunogen in incomplete Freund’s adjuvant (HIV-1 immunogen, REMUNE) in human immunodeficiency virus type-1 seropositive subjects</article-title>
<source>Viral Immunol</source>
<year>1997</year>
<volume>10</volume>
<fpage>221</fpage>
<lpage>228</lpage>
<pub-id pub-id-type="pmid">9473153</pub-id>
</element-citation>
</ref>
<ref id="B69"><label>69</label>
<element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Kang</surname>
<given-names>CY</given-names>
</name>
<name><surname>Michalski</surname>
<given-names>C</given-names>
</name>
</person-group>
<source>HIV combination vaccine and prime boost</source>
<publisher-name>Google Patents</publisher-name>
<year>2011</year>
</element-citation>
</ref>
<ref id="B70"><label>70</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rossio</surname>
<given-names>JL</given-names>
</name>
<name><surname>Esser</surname>
<given-names>MT</given-names>
</name>
<name><surname>Suryanarayana</surname>
<given-names>K</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Inactivation of human immunodeficiency virus type 1 infectivity with preservation of conformational and functional integrity of virion surface proteins</article-title>
<source>J Virol</source>
<year>1998</year>
<volume>72</volume>
<fpage>7992</fpage>
<lpage>8001</lpage>
<pub-id pub-id-type="pmid">9733838</pub-id>
</element-citation>
</ref>
<ref id="B71"><label>71</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sheppard</surname>
<given-names>HW</given-names>
</name>
</person-group>
<article-title>Inactivated- or killed-virus HIV/AIDS vaccines</article-title>
<source>Curr Drug Targets Infect Disord</source>
<year>2005</year>
<volume>5</volume>
<fpage>131</fpage>
<lpage>141</lpage>
<pub-id pub-id-type="pmid">15975019</pub-id>
</element-citation>
</ref>
<ref id="B72"><label>72</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Patel</surname>
<given-names>SS</given-names>
</name>
<name><surname>Wagstaff</surname>
<given-names>AJ</given-names>
</name>
</person-group>
<article-title>A cellular pertussis vaccine (Infanrix-DTPa; SB-3): a review of its immunogenicity, protective efficacy and tolerability in the prevention of Bordetella pertussis infection</article-title>
<source>Drugs</source>
<year>1996</year>
<volume>52</volume>
<fpage>254</fpage>
<lpage>275</lpage>
<pub-id pub-id-type="pmid">8841742</pub-id>
</element-citation>
</ref>
<ref id="B73"><label>73</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cherry</surname>
<given-names>JD</given-names>
</name>
</person-group>
<article-title>Historical review of pertussis and the classical vaccine</article-title>
<source>J Infect Dis</source>
<year>1996</year>
<volume>174</volume>
<issue>Suppl 3</issue>
<fpage>S259</fpage>
<lpage>S263</lpage>
<pub-id pub-id-type="pmid">8896526</pub-id>
</element-citation>
</ref>
<ref id="B74"><label>74</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Grabenstein</surname>
<given-names>JD</given-names>
</name>
</person-group>
<article-title>Anthrax vaccine: a review</article-title>
<source>Immunol Allergy Clin North Am</source>
<year>2003</year>
<volume>23</volume>
<fpage>713</fpage>
<lpage>730</lpage>
<pub-id pub-id-type="pmid">14753388</pub-id>
</element-citation>
</ref>
<ref id="B75"><label>75</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Buddle</surname>
<given-names>BM</given-names>
</name>
<name><surname>Aldwell</surname>
<given-names>FE</given-names>
</name>
<name><surname>Skinner</surname>
<given-names>MA</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Effect of oral vaccination of cattle with lipid-formulated BCG on immune responses and protection against bovine tuberculosis</article-title>
<source>Vaccine</source>
<year>2005</year>
<volume>23</volume>
<fpage>3581</fpage>
<lpage>3589</lpage>
<pub-id pub-id-type="pmid">15855017</pub-id>
</element-citation>
</ref>
<ref id="B76"><label>76</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Secanella-Fandos</surname>
<given-names>S</given-names>
</name>
<name><surname>Noguera-Ortega</surname>
<given-names>E</given-names>
</name>
<name><surname>Olivares</surname>
<given-names>F</given-names>
</name>
<name><surname>Luquin</surname>
<given-names>M</given-names>
</name>
<name><surname>Julian</surname>
<given-names>E</given-names>
</name>
</person-group>
<article-title>Killed but metabolically active Mycobacterium bovis bacillus Calmette-Guerin retains the antitumor ability of live bacillus Calmette-Guerin</article-title>
<source>J Urol</source>
<year>2014</year>
<volume>191</volume>
<fpage>1422</fpage>
<lpage>1428</lpage>
<pub-id pub-id-type="pmid">24333111</pub-id>
</element-citation>
</ref>
<ref id="B77"><label>77</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sanakkayala</surname>
<given-names>N</given-names>
</name>
<name><surname>Sokolovska</surname>
<given-names>A</given-names>
</name>
<name><surname>Gulani</surname>
<given-names>J</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Induction of antigen-specific Th1-type immune responses by gamma-irradiated recombinant Brucella abortus RB51</article-title>
<source>Clin Diagn Lab Immunol</source>
<year>2005</year>
<volume>12</volume>
<fpage>1429</fpage>
<lpage>1436</lpage>
<pub-id pub-id-type="pmid">16339067</pub-id>
</element-citation>
</ref>
<ref id="B78"><label>78</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yamamoto</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title>Current status of cholera and rise of novel mucosal vaccine</article-title>
<source>Jpn J Infect Dis</source>
<year>2000</year>
<volume>53</volume>
<fpage>181</fpage>
<lpage>188</lpage>
<pub-id pub-id-type="pmid">11135702</pub-id>
</element-citation>
</ref>
<ref id="B79"><label>79</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kabir</surname>
<given-names>S</given-names>
</name>
</person-group>
<article-title>Cholera vaccines: the current status and problems</article-title>
<source>Rev Med Microbiol</source>
<year>2005</year>
<volume>16</volume>
<fpage>101</fpage>
<lpage>116</lpage>
</element-citation>
</ref>
<ref id="B80"><label>80</label>
<element-citation publication-type="book"><collab>MDS</collab>
<source>Development of 60Co-irradiated cholera vaccine [Internet]</source>
<publisher-loc>Niigata</publisher-loc>
<publisher-name>Niigata University Graduate School of Medical and Dental Science</publisher-name>
<date-in-citation content-type="access-date">cited 2015 Mar 2</date-in-citation>
<comment>Available from: <ext-link ext-link-type="uri" xlink:href="http://www.mds.niigata-u.ac.jp/topics/index.html">http://www.mds.niigata-u.ac.jp/topics/index.html</ext-link>
</comment>
</element-citation>
</ref>
<ref id="B81"><label>81</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pasnik</surname>
<given-names>DJ</given-names>
</name>
<name><surname>Evans</surname>
<given-names>JJ</given-names>
</name>
<name><surname>Klesius</surname>
<given-names>PH</given-names>
</name>
</person-group>
<article-title>A microwave-irradiated Streptococcus agalactiae vaccine provides partial protection against experimental challenge in Nile Tilapia, Oreochromis niloticus</article-title>
<source>World J Vaccines</source>
<year>2014</year>
<volume>4</volume>
<fpage>184</fpage>
<lpage>189</lpage>
</element-citation>
</ref>
<ref id="B82"><label>82</label>
<element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Tuasikal</surname>
<given-names>BJ</given-names>
</name>
</person-group>
<source>Streptococcus agalactiae irradiated vaccine candidate for subclinical mastitis prevention in ruminants [dissertation]</source>
<publisher-loc>Bogor</publisher-loc>
<publisher-name>Bogor Agricultural University</publisher-name>
<year>2012</year>
</element-citation>
</ref>
<ref id="B83"><label>83</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tuasikal</surname>
<given-names>BJ</given-names>
</name>
<name><surname>Wibawan</surname>
<given-names>IW</given-names>
</name>
<name><surname>Pasaribu</surname>
<given-names>FH</given-names>
</name>
<name><surname>Estuningsih</surname>
<given-names>S</given-names>
</name>
</person-group>
<article-title>Bacterial protein characterization of Streptococcus agalactiae by SDS-PAGE method for subclinical mastitis irradiated vaccine materials in dairy cattle</article-title>
<source>Atom Indonesia</source>
<year>2012</year>
<volume>38</volume>
<fpage>66</fpage>
<lpage>70</lpage>
</element-citation>
</ref>
<ref id="B84"><label>84</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gaidamakova</surname>
<given-names>EK</given-names>
</name>
<name><surname>Myles</surname>
<given-names>IA</given-names>
</name>
<name><surname>McDaniel</surname>
<given-names>DP</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Preserving immunogenicity of lethally irradiated viral and bacterial vaccine epitopes using a radio-protective Mn2+-Peptide complex from Deinococcus</article-title>
<source>Cell Host Microbe</source>
<year>2012</year>
<volume>12</volume>
<fpage>117</fpage>
<lpage>124</lpage>
<pub-id pub-id-type="pmid">22817993</pub-id>
</element-citation>
</ref>
<ref id="B85"><label>85</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van Diemen</surname>
<given-names>PM</given-names>
</name>
<name><surname>Yamaguchi</surname>
<given-names>Y</given-names>
</name>
<name><surname>Paterson</surname>
<given-names>GK</given-names>
</name>
<name><surname>Rollier</surname>
<given-names>CS</given-names>
</name>
<name><surname>Hill</surname>
<given-names>AV</given-names>
</name>
<name><surname>Wyllie</surname>
<given-names>DH</given-names>
</name>
</person-group>
<article-title>Irradiated wild-type and Spa mutant Staphylococcus aureus induce anti-S. aureus immune responses in mice which do not protect against subsequent intravenous challenge</article-title>
<source>Pathog Dis</source>
<year>2013</year>
<volume>68</volume>
<fpage>20</fpage>
<lpage>26</lpage>
<pub-id pub-id-type="pmid">23620394</pub-id>
</element-citation>
</ref>
<ref id="B86"><label>86</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Burnside</surname>
<given-names>K</given-names>
</name>
<name><surname>Lembo</surname>
<given-names>A</given-names>
</name>
<name><surname>Harrell</surname>
<given-names>MI</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Vaccination with a UV-irradiated genetically attenuated mutant of Staphylococcus aureus provides protection against subsequent systemic infection</article-title>
<source>J Infect Dis</source>
<year>2012</year>
<volume>206</volume>
<fpage>1734</fpage>
<lpage>1744</lpage>
<pub-id pub-id-type="pmid">22966130</pub-id>
</element-citation>
</ref>
<ref id="B87"><label>87</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Malley</surname>
<given-names>R</given-names>
</name>
<name><surname>Srivastava</surname>
<given-names>A</given-names>
</name>
<name><surname>Lipsitch</surname>
<given-names>M</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Antibody-independent, interleukin-17A-mediated, cross-serotype immunity to pneumococci in mice immunized intranasally with the cell wall polysaccharide</article-title>
<source>Infect Immun</source>
<year>2006</year>
<volume>74</volume>
<fpage>2187</fpage>
<lpage>2195</lpage>
<pub-id pub-id-type="pmid">16552049</pub-id>
</element-citation>
</ref>
<ref id="B88"><label>88</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Malley</surname>
<given-names>R</given-names>
</name>
<name><surname>Lipsitch</surname>
<given-names>M</given-names>
</name>
<name><surname>Stack</surname>
<given-names>A</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Intranasal immunization with killed unencapsulated whole cells prevents colonization and invasive disease by capsulated pneumococci</article-title>
<source>Infect Immun</source>
<year>2001</year>
<volume>69</volume>
<fpage>4870</fpage>
<lpage>4873</lpage>
<pub-id pub-id-type="pmid">11447162</pub-id>
</element-citation>
</ref>
<ref id="B89"><label>89</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname>
<given-names>SB</given-names>
</name>
<name><surname>Kim</surname>
<given-names>SJ</given-names>
</name>
<name><surname>Lee</surname>
<given-names>BM</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Oral administration of Salmonella enterica serovar Typhimurium expressing swine interleukin-18 induces Th1-biased protective immunity against inactivated vaccine of pseudorabies virus</article-title>
<source>Vet Microbiol</source>
<year>2012</year>
<volume>155</volume>
<fpage>172</fpage>
<lpage>182</lpage>
<pub-id pub-id-type="pmid">21940117</pub-id>
</element-citation>
</ref>
<ref id="B90"><label>90</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rahman</surname>
<given-names>MM</given-names>
</name>
<name><surname>Uyangaa</surname>
<given-names>E</given-names>
</name>
<name><surname>Han</surname>
<given-names>YW</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Enhancement of Th1-biased protective immunity against avian influenza H9N2 virus via oral co-administration of attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-alpha and interleukin-18 along with an inactivated vaccine</article-title>
<source>BMC Vet Res</source>
<year>2012</year>
<volume>8</volume>
<fpage>105</fpage>
<pub-id pub-id-type="pmid">22776696</pub-id>
</element-citation>
</ref>
<ref id="B91"><label>91</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eldar</surname>
<given-names>A</given-names>
</name>
<name><surname>Shapiro</surname>
<given-names>O</given-names>
</name>
<name><surname>Bejerano</surname>
<given-names>Y</given-names>
</name>
<name><surname>Bercovier</surname>
<given-names>H</given-names>
</name>
</person-group>
<article-title>Vaccination with whole-cell vaccine and bacterial protein extract protects tilapia against Streptococcus difficile meningoencephalitis</article-title>
<source>Vaccine</source>
<year>1995</year>
<volume>13</volume>
<fpage>867</fpage>
<lpage>870</lpage>
<pub-id pub-id-type="pmid">7483810</pub-id>
</element-citation>
</ref>
<ref id="B92"><label>92</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liberman</surname>
<given-names>C</given-names>
</name>
<name><surname>Takagi</surname>
<given-names>M</given-names>
</name>
<name><surname>Cabrera-Crespo</surname>
<given-names>J</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Pneumococcal whole-cell vaccine: optimization of cell growth of unencapsulated Streptococcus pneumoniae in bioreactor using animal-free medium</article-title>
<source>J Ind Microbiol Biotechnol</source>
<year>2008</year>
<volume>35</volume>
<fpage>1441</fpage>
<lpage>1445</lpage>
<pub-id pub-id-type="pmid">18712539</pub-id>
</element-citation>
</ref>
<ref id="B93"><label>93</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chawla</surname>
<given-names>S</given-names>
</name>
<name><surname>Garg</surname>
<given-names>D</given-names>
</name>
<name><surname>Jain</surname>
<given-names>RB</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Tuberculosis vaccine: time to look into future</article-title>
<source>Hum Vaccin Immunother</source>
<year>2014</year>
<volume>10</volume>
<fpage>420</fpage>
<lpage>422</lpage>
<pub-id pub-id-type="pmid">24231233</pub-id>
</element-citation>
</ref>
<ref id="B94"><label>94</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kaufmann</surname>
<given-names>SH</given-names>
</name>
</person-group>
<article-title>Tuberculosis vaccine development at a divide</article-title>
<source>Curr Opin Pulm Med</source>
<year>2014</year>
<volume>20</volume>
<fpage>294</fpage>
<lpage>300</lpage>
<pub-id pub-id-type="pmid">24626237</pub-id>
</element-citation>
</ref>
<ref id="B95"><label>95</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kaufmann</surname>
<given-names>SH</given-names>
</name>
<name><surname>Lange</surname>
<given-names>C</given-names>
</name>
<name><surname>Rao</surname>
<given-names>M</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Progress in tuberculosis vaccine development and host-directed therapies: a state of the art review</article-title>
<source>Lancet Respir Med</source>
<year>2014</year>
<volume>2</volume>
<fpage>301</fpage>
<lpage>320</lpage>
<pub-id pub-id-type="pmid">24717627</pub-id>
</element-citation>
</ref>
<ref id="B96"><label>96</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cha</surname>
<given-names>SB</given-names>
</name>
<name><surname>Shin</surname>
<given-names>SJ</given-names>
</name>
</person-group>
<article-title>Mycobacterium bovis Bacillus Calmette-Guerin (BCG) and BCG-based vaccines against tuberculosis</article-title>
<source>J Bacteriol Virol</source>
<year>2014</year>
<volume>44</volume>
<fpage>236</fpage>
<lpage>243</lpage>
</element-citation>
</ref>
<ref id="B97"><label>97</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>White</surname>
<given-names>AD</given-names>
</name>
<name><surname>Sibley</surname>
<given-names>L</given-names>
</name>
<name><surname>Dennis</surname>
<given-names>MJ</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Evaluation of the safety and immunogenicity of a candidate tuberculosis vaccine, MVA85A, delivered by aerosol to the lungs of macaques</article-title>
<source>Clin Vaccine Immunol</source>
<year>2013</year>
<volume>20</volume>
<fpage>663</fpage>
<lpage>672</lpage>
<pub-id pub-id-type="pmid">23446219</pub-id>
</element-citation>
</ref>
<ref id="B98"><label>98</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Davids</surname>
<given-names>V</given-names>
</name>
<name><surname>Hanekom</surname>
<given-names>W</given-names>
</name>
<name><surname>Gelderbloem</surname>
<given-names>SJ</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Dose-dependent immune response to Mycobacterium bovis BCG vaccination in neonates</article-title>
<source>Clin Vaccine Immunol</source>
<year>2007</year>
<volume>14</volume>
<fpage>198</fpage>
<lpage>200</lpage>
<pub-id pub-id-type="pmid">17182761</pub-id>
</element-citation>
</ref>
<ref id="B99"><label>99</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McShane</surname>
<given-names>H</given-names>
</name>
<name><surname>Williams</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>A review of preclinical animal models utilised for TB vaccine evaluation in the context of recent human efficacy data</article-title>
<source>Tuberculosis (Edinb)</source>
<year>2014</year>
<volume>94</volume>
<fpage>105</fpage>
<lpage>110</lpage>
<pub-id pub-id-type="pmid">24369986</pub-id>
</element-citation>
</ref>
<ref id="B100"><label>100</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>da Costa</surname>
<given-names>C</given-names>
</name>
<name><surname>Walker</surname>
<given-names>B</given-names>
</name>
<name><surname>Bonavia</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>Tuberculosis vaccines: state of the art, and novel approaches to vaccine development</article-title>
<source>Int J Infect Dis</source>
<year>2015</year>
<volume>32</volume>
<fpage>5</fpage>
<lpage>12</lpage>
<pub-id pub-id-type="pmid">25809749</pub-id>
</element-citation>
</ref>
<ref id="B101"><label>101</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mayo</surname>
<given-names>RE</given-names>
</name>
<name><surname>Stanford</surname>
<given-names>JL</given-names>
</name>
</person-group>
<article-title>Double-blind placebo-controlled trial of Mycobacterium vaccae immunotherapy for tuberculosis in KwaZulu, South Africa, 1991-97</article-title>
<source>Trans R Soc Trop Med Hyg</source>
<year>2000</year>
<volume>94</volume>
<fpage>563</fpage>
<lpage>568</lpage>
<pub-id pub-id-type="pmid">11132390</pub-id>
</element-citation>
</ref>
<ref id="B102"><label>102</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>von Reyn</surname>
<given-names>CF</given-names>
</name>
<name><surname>Mtei</surname>
<given-names>L</given-names>
</name>
<name><surname>Arbeit</surname>
<given-names>RD</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Prevention of tuberculosis in Bacille Calmette-Guerin-primed, HIV-infected adults boosted with an inactivated whole-cell mycobacterial vaccine</article-title>
<source>AIDS</source>
<year>2010</year>
<volume>24</volume>
<fpage>675</fpage>
<lpage>685</lpage>
<pub-id pub-id-type="pmid">20118767</pub-id>
</element-citation>
</ref>
<ref id="B103"><label>103</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Johnson</surname>
<given-names>JL</given-names>
</name>
<name><surname>Kamya</surname>
<given-names>RM</given-names>
</name>
<name><surname>Okwera</surname>
<given-names>A</given-names>
</name>
<etal></etal>
</person-group>
<collab>The Uganda-Case Western Reserve University Research Collaboration</collab>
<article-title>Randomized controlled trial of Mycobacterium vaccae immunotherapy in non-human immunodeficiency virus-infected ugandan adults with newly diagnosed pulmonary tuberculosis</article-title>
<source>J Infect Dis</source>
<year>2000</year>
<volume>181</volume>
<fpage>1304</fpage>
<lpage>1312</lpage>
<pub-id pub-id-type="pmid">10753731</pub-id>
</element-citation>
</ref>
<ref id="B104"><label>104</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Olson</surname>
<given-names>BJ</given-names>
</name>
<name><surname>Habel</surname>
<given-names>K</given-names>
</name>
<name><surname>Piggott</surname>
<given-names>WR</given-names>
</name>
</person-group>
<article-title>A comparative study of live and killed vaccines in experimental tuberculosis</article-title>
<source>Public Health Rep</source>
<year>1947</year>
<volume>62</volume>
<fpage>293</fpage>
<lpage>296</lpage>
<pub-id pub-id-type="pmid">20341594</pub-id>
</element-citation>
</ref>
<ref id="B105"><label>105</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Paterson</surname>
<given-names>JC</given-names>
</name>
<name><surname>Crombie</surname>
<given-names>DW</given-names>
</name>
<name><surname>Coles</surname>
<given-names>JC</given-names>
</name>
</person-group>
<article-title>Protection by killed vole bacillus vaccine against experimental tuberculosis in guinea pigs</article-title>
<source>Can J Res E Med Sci</source>
<year>1949</year>
<volume>27</volume>
<fpage>37</fpage>
<lpage>42</lpage>
<pub-id pub-id-type="pmid">18124252</pub-id>
</element-citation>
</ref>
<ref id="B106"><label>106</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>O'Brien</surname>
<given-names>KL</given-names>
</name>
</person-group>
<article-title>PCV13 impact evaluations: the obvious and the unpredicted</article-title>
<source>Pediatr Infect Dis J</source>
<year>2013</year>
<volume>32</volume>
<fpage>264</fpage>
<lpage>265</lpage>
<pub-id pub-id-type="pmid">23558322</pub-id>
</element-citation>
</ref>
<ref id="B107"><label>107</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dagan</surname>
<given-names>R</given-names>
</name>
<name><surname>Juergens</surname>
<given-names>C</given-names>
</name>
<name><surname>Trammel</surname>
<given-names>J</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) versus that of 7-valent PCV (PCV7) against nasopharyngeal colonization of antibiotic-nonsusceptible Streptococcus pneumoniae</article-title>
<source>J Infect Dis</source>
<year>2015</year>
<volume>211</volume>
<fpage>1144</fpage>
<lpage>1153</lpage>
<pub-id pub-id-type="pmid">25355940</pub-id>
</element-citation>
</ref>
<ref id="B108"><label>108</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chapman</surname>
<given-names>KE</given-names>
</name>
<name><surname>Wilson</surname>
<given-names>D</given-names>
</name>
<name><surname>Gorton</surname>
<given-names>R</given-names>
</name>
</person-group>
<article-title>Serotype dynamics of invasive pneumococcal disease post-PCV7 and pre-PCV13 introduction in North East England</article-title>
<source>Epidemiol Infect</source>
<year>2013</year>
<volume>141</volume>
<fpage>344</fpage>
<lpage>352</lpage>
<pub-id pub-id-type="pmid">22564258</pub-id>
</element-citation>
</ref>
<ref id="B109"><label>109</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goncalves</surname>
<given-names>VM</given-names>
</name>
<name><surname>Dias</surname>
<given-names>WO</given-names>
</name>
<name><surname>Campos</surname>
<given-names>IB</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Development of a whole cell pneumococcal vaccine: BPL inactivation, cGMP production, and stability</article-title>
<source>Vaccine</source>
<year>2014</year>
<volume>32</volume>
<fpage>1113</fpage>
<lpage>1120</lpage>
<pub-id pub-id-type="pmid">24342254</pub-id>
</element-citation>
</ref>
<ref id="B110"><label>110</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moffitt</surname>
<given-names>KL</given-names>
</name>
<name><surname>Yadav</surname>
<given-names>P</given-names>
</name>
<name><surname>Weinberger</surname>
<given-names>DM</given-names>
</name>
<name><surname>Anderson</surname>
<given-names>PW</given-names>
</name>
<name><surname>Malley</surname>
<given-names>R</given-names>
</name>
</person-group>
<article-title>Broad antibody and T cell reactivity induced by a pneumococcal whole-cell vaccine</article-title>
<source>Vaccine</source>
<year>2012</year>
<volume>30</volume>
<fpage>4316</fpage>
<lpage>4322</lpage>
<pub-id pub-id-type="pmid">22682288</pub-id>
</element-citation>
</ref>
<ref id="B111"><label>111</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lu</surname>
<given-names>YJ</given-names>
</name>
<name><surname>Leite</surname>
<given-names>L</given-names>
</name>
<name><surname>Goncalves</surname>
<given-names>VM</given-names>
</name>
<etal></etal>
</person-group>
<article-title>GMP-grade pneumococcal whole-cell vaccine injected subcutaneously protects mice from nasopharyngeal colonization and fatal aspiration-sepsis</article-title>
<source>Vaccine</source>
<year>2010</year>
<volume>28</volume>
<fpage>7468</fpage>
<lpage>7475</lpage>
<pub-id pub-id-type="pmid">20858450</pub-id>
</element-citation>
</ref>
<ref id="B112"><label>112</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Coburn</surname>
<given-names>B</given-names>
</name>
<name><surname>Grassl</surname>
<given-names>GA</given-names>
</name>
<name><surname>Finlay</surname>
<given-names>BB</given-names>
</name>
</person-group>
<article-title>Salmonella, the host and disease: a brief review</article-title>
<source>Immunol Cell Biol</source>
<year>2007</year>
<volume>85</volume>
<fpage>112</fpage>
<lpage>118</lpage>
<pub-id pub-id-type="pmid">17146467</pub-id>
</element-citation>
</ref>
<ref id="B113"><label>113</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname>
<given-names>K</given-names>
</name>
<name><surname>Shim</surname>
<given-names>J</given-names>
</name>
<name><surname>Park</surname>
<given-names>S</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Evaluation of immune response for Vi-CRM(197) conjugated vaccine against Salmonella enterica serovar Typhi in mice</article-title>
<source>J Bacteriol Virol</source>
<year>2014</year>
<volume>44</volume>
<fpage>52</fpage>
<lpage>58</lpage>
</element-citation>
</ref>
<ref id="B114"><label>114</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Previte</surname>
<given-names>JJ</given-names>
</name>
</person-group>
<article-title>Immunogenicity of irradiated Salmonella typhimurium cells and endotoxin</article-title>
<source>J Bacteriol</source>
<year>1968</year>
<volume>95</volume>
<fpage>2165</fpage>
<lpage>2170</lpage>
<pub-id pub-id-type="pmid">4876130</pub-id>
</element-citation>
</ref>
<ref id="B115"><label>115</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dima</surname>
<given-names>FV</given-names>
</name>
<name><surname>Ivanov</surname>
<given-names>D</given-names>
</name>
<name><surname>Dima</surname>
<given-names>SV</given-names>
</name>
</person-group>
<article-title>Active immunization against Salmonella typhi by oral administration of fast neutron irradiated cells</article-title>
<source>Ann N Y Acad Sci</source>
<year>1994</year>
<volume>730</volume>
<fpage>348</fpage>
<lpage>349</lpage>
<pub-id pub-id-type="pmid">8080207</pub-id>
</element-citation>
</ref>
<ref id="B116"><label>116</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Begum</surname>
<given-names>RH</given-names>
</name>
<name><surname>Rahman</surname>
<given-names>H</given-names>
</name>
<name><surname>Ahmed</surname>
<given-names>G</given-names>
</name>
</person-group>
<article-title>Development and evaluation of gamma irradiated toxoid vaccine of Salmonella enterica var Typhimurium</article-title>
<source>Vet Microbiol</source>
<year>2011</year>
<volume>153</volume>
<fpage>191</fpage>
<lpage>197</lpage>
<pub-id pub-id-type="pmid">21763085</pub-id>
</element-citation>
</ref>
<ref id="B117"><label>117</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Elzer</surname>
<given-names>PH</given-names>
</name>
<name><surname>Edmonds</surname>
<given-names>MD</given-names>
</name>
<name><surname>Hagius</surname>
<given-names>SD</given-names>
</name>
<name><surname>Walker</surname>
<given-names>JV</given-names>
</name>
<name><surname>Gilsdorf</surname>
<given-names>MJ</given-names>
</name>
<name><surname>Davis</surname>
<given-names>DS</given-names>
</name>
</person-group>
<article-title>Safety of Brucella abortus strain RB51 in Bison</article-title>
<source>J Wildl Dis</source>
<year>1998</year>
<volume>34</volume>
<fpage>825</fpage>
<lpage>829</lpage>
<pub-id pub-id-type="pmid">9813857</pub-id>
</element-citation>
</ref>
<ref id="B118"><label>118</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Olsen</surname>
<given-names>SC</given-names>
</name>
<name><surname>Holland</surname>
<given-names>SD</given-names>
</name>
</person-group>
<article-title>Safety of revaccination of pregnant bison with Brucella abortus strain RB51</article-title>
<source>J Wildl Dis</source>
<year>2003</year>
<volume>39</volume>
<fpage>824</fpage>
<lpage>829</lpage>
<pub-id pub-id-type="pmid">14733277</pub-id>
</element-citation>
</ref>
<ref id="B119"><label>119</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ahn</surname>
<given-names>TH</given-names>
</name>
<name><surname>Nishihara</surname>
<given-names>H</given-names>
</name>
<name><surname>Carpenter</surname>
<given-names>CM</given-names>
</name>
<name><surname>Taplin</surname>
<given-names>GV</given-names>
</name>
</person-group>
<article-title>Respiration of gamma irradiated Brucella abortus and Mycobacterium tuberculosis</article-title>
<source>Proc Soc Exp Biol Med</source>
<year>1962</year>
<volume>111</volume>
<fpage>771</fpage>
<lpage>773</lpage>
<pub-id pub-id-type="pmid">14011360</pub-id>
</element-citation>
</ref>
<ref id="B120"><label>120</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nishihara</surname>
<given-names>H</given-names>
</name>
<name><surname>Ahn</surname>
<given-names>TH</given-names>
</name>
<name><surname>Taplin</surname>
<given-names>GV</given-names>
</name>
<name><surname>Carpenter</surname>
<given-names>CM</given-names>
</name>
</person-group>
<article-title>Immunogenicity of a gamma-irradiated Brucella melitensis vaccine in mice</article-title>
<source>Cornell Vet</source>
<year>1964</year>
<volume>54</volume>
<fpage>573</fpage>
<lpage>583</lpage>
<pub-id pub-id-type="pmid">14234061</pub-id>
</element-citation>
</ref>
<ref id="B121"><label>121</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oliveira</surname>
<given-names>SC</given-names>
</name>
<name><surname>Zhu</surname>
<given-names>Y</given-names>
</name>
<name><surname>Splitter</surname>
<given-names>GA</given-names>
</name>
</person-group>
<article-title>Recombinant L7/L12 ribosomal protein and gamma-irradiated Brucella abortus induce a T-helper 1 subset response from murine CD4+ T cells</article-title>
<source>Immunology</source>
<year>1994</year>
<volume>83</volume>
<fpage>659</fpage>
<lpage>664</lpage>
<pub-id pub-id-type="pmid">7875746</pub-id>
</element-citation>
</ref>
<ref id="B122"><label>122</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Surendran</surname>
<given-names>N</given-names>
</name>
<name><surname>Hiltbold</surname>
<given-names>EM</given-names>
</name>
<name><surname>Heid</surname>
<given-names>B</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Heat-killed and gamma-irradiated Brucella strain RB51 stimulates enhanced dendritic cell activation, but not function compared with the virulent smooth strain 2308</article-title>
<source>FEMS Immunol Med Microbiol</source>
<year>2010</year>
<volume>60</volume>
<fpage>147</fpage>
<lpage>155</lpage>
<pub-id pub-id-type="pmid">20812951</pub-id>
</element-citation>
</ref>
<ref id="B123"><label>123</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moustafa</surname>
<given-names>D</given-names>
</name>
<name><surname>Garg</surname>
<given-names>VK</given-names>
</name>
<name><surname>Jain</surname>
<given-names>N</given-names>
</name>
<name><surname>Sriranganathan</surname>
<given-names>N</given-names>
</name>
<name><surname>Vemulapalli</surname>
<given-names>R</given-names>
</name>
</person-group>
<article-title>Immunization of mice with gamma-irradiated Brucella neotomae and its recombinant strains induces protection against virulent B. abortus, B. melitensis, and B. suis challenge</article-title>
<source>Vaccine</source>
<year>2011</year>
<volume>29</volume>
<fpage>784</fpage>
<lpage>794</lpage>
<pub-id pub-id-type="pmid">21109033</pub-id>
</element-citation>
</ref>
<ref id="B124"><label>124</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dabral</surname>
<given-names>N</given-names>
</name>
<name><surname>Martha Moreno</surname>
<given-names>L</given-names>
</name>
<name><surname>Sriranganathan</surname>
<given-names>N</given-names>
</name>
<name><surname>Vemulapalli</surname>
<given-names>R</given-names>
</name>
</person-group>
<article-title>Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308</article-title>
<source>PLoS One</source>
<year>2014</year>
<volume>9</volume>
<fpage>e107180</fpage>
<pub-id pub-id-type="pmid">25225910</pub-id>
</element-citation>
</ref>
<ref id="B125"><label>125</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gething</surname>
<given-names>PW</given-names>
</name>
<name><surname>Patil</surname>
<given-names>AP</given-names>
</name>
<name><surname>Smith</surname>
<given-names>DL</given-names>
</name>
<etal></etal>
</person-group>
<article-title>A new world malaria map: Plasmodium falciparum endemicity in 2010</article-title>
<source>Malar J</source>
<year>2011</year>
<volume>10</volume>
<fpage>378</fpage>
<pub-id pub-id-type="pmid">22185615</pub-id>
</element-citation>
</ref>
<ref id="B126"><label>126</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schwartz</surname>
<given-names>L</given-names>
</name>
<name><surname>Brown</surname>
<given-names>GV</given-names>
</name>
<name><surname>Genton</surname>
<given-names>B</given-names>
</name>
<name><surname>Moorthy</surname>
<given-names>VS</given-names>
</name>
</person-group>
<article-title>A review of malaria vaccine clinical projects based on the WHO rainbow table</article-title>
<source>Malar J</source>
<year>2012</year>
<volume>11</volume>
<fpage>11</fpage>
<pub-id pub-id-type="pmid">22230255</pub-id>
</element-citation>
</ref>
<ref id="B127"><label>127</label>
<element-citation publication-type="journal"><article-title>In brief: PCV13 for adults 65 years and older</article-title>
<source>Med Lett Drugs Ther</source>
<year>2014</year>
<volume>56</volume>
<fpage>102</fpage>
<pub-id pub-id-type="pmid">25296261</pub-id>
</element-citation>
</ref>
<ref id="B128"><label>128</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Okie</surname>
<given-names>S</given-names>
</name>
</person-group>
<article-title>Betting on a malaria vaccine</article-title>
<source>N Engl J Med</source>
<year>2005</year>
<volume>353</volume>
<fpage>1877</fpage>
<lpage>1881</lpage>
<pub-id pub-id-type="pmid">16267316</pub-id>
</element-citation>
</ref>
<ref id="B129"><label>129</label>
<element-citation publication-type="journal"><collab>RTS,S Clinical Trials Partnership</collab>
<person-group person-group-type="author"><name><surname>Agnandji</surname>
<given-names>ST</given-names>
</name>
<name><surname>Lell</surname>
<given-names>B</given-names>
</name>
<etal></etal>
</person-group>
<article-title>A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants</article-title>
<source>N Engl J Med</source>
<year>2012</year>
<volume>367</volume>
<fpage>2284</fpage>
<lpage>2295</lpage>
<pub-id pub-id-type="pmid">23136909</pub-id>
</element-citation>
</ref>
<ref id="B130"><label>130</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Russell</surname>
<given-names>PF</given-names>
</name>
<name><surname>Mohan</surname>
<given-names>BN</given-names>
</name>
</person-group>
<article-title>The immunization of fowls against mosquito-borne Plasmodium gallinaceum by injections of serum and of inactivated homologous sporozoites</article-title>
<source>J Exp Med</source>
<year>1942</year>
<volume>76</volume>
<fpage>477</fpage>
<lpage>495</lpage>
<pub-id pub-id-type="pmid">19871251</pub-id>
</element-citation>
</ref>
<ref id="B131"><label>131</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nussenzweig</surname>
<given-names>RS</given-names>
</name>
<name><surname>Vanderberg</surname>
<given-names>J</given-names>
</name>
<name><surname>Most</surname>
<given-names>H</given-names>
</name>
<name><surname>Orton</surname>
<given-names>C</given-names>
</name>
</person-group>
<article-title>Protective immunity produced by the injection of x-irradiated sporozoites of plasmodium berghei</article-title>
<source>Nature</source>
<year>1967</year>
<volume>216</volume>
<fpage>160</fpage>
<lpage>162</lpage>
<pub-id pub-id-type="pmid">6057225</pub-id>
</element-citation>
</ref>
<ref id="B132"><label>132</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hoffman</surname>
<given-names>SL</given-names>
</name>
<name><surname>Goh</surname>
<given-names>LM</given-names>
</name>
<name><surname>Luke</surname>
<given-names>TC</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites</article-title>
<source>J Infect Dis</source>
<year>2002</year>
<volume>185</volume>
<fpage>1155</fpage>
<lpage>1164</lpage>
<pub-id pub-id-type="pmid">11930326</pub-id>
</element-citation>
</ref>
<ref id="B133"><label>133</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Roestenberg</surname>
<given-names>M</given-names>
</name>
<name><surname>McCall</surname>
<given-names>M</given-names>
</name>
<name><surname>Hopman</surname>
<given-names>J</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Protection against a malaria challenge by sporozoite inoculation</article-title>
<source>N Engl J Med</source>
<year>2009</year>
<volume>361</volume>
<fpage>468</fpage>
<lpage>477</lpage>
<pub-id pub-id-type="pmid">19641203</pub-id>
</element-citation>
</ref>
<ref id="B134"><label>134</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Roestenberg</surname>
<given-names>M</given-names>
</name>
<name><surname>Teirlinck</surname>
<given-names>AC</given-names>
</name>
<name><surname>McCall</surname>
<given-names>MB</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Long-term protection against malaria after experimental sporozoite inoculation: an open-label follow-up study</article-title>
<source>Lancet</source>
<year>2011</year>
<volume>377</volume>
<fpage>1770</fpage>
<lpage>1776</lpage>
<pub-id pub-id-type="pmid">21514658</pub-id>
</element-citation>
</ref>
<ref id="B135"><label>135</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Laurens</surname>
<given-names>MB</given-names>
</name>
<name><surname>Billingsley</surname>
<given-names>P</given-names>
</name>
<name><surname>Richman</surname>
<given-names>A</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Successful human infection with P. falciparum using three aseptic Anopheles stephensi mosquitoes: a new model for controlled human malaria infection</article-title>
<source>PLoS One</source>
<year>2013</year>
<volume>8</volume>
<fpage>e68969</fpage>
<pub-id pub-id-type="pmid">23874828</pub-id>
</element-citation>
</ref>
<ref id="B136"><label>136</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Seder</surname>
<given-names>RA</given-names>
</name>
<name><surname>Chang</surname>
<given-names>LJ</given-names>
</name>
<name><surname>Enama</surname>
<given-names>ME</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine</article-title>
<source>Science</source>
<year>2013</year>
<volume>341</volume>
<fpage>1359</fpage>
<lpage>1365</lpage>
<pub-id pub-id-type="pmid">23929949</pub-id>
</element-citation>
</ref>
<ref id="B137"><label>137</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Epstein</surname>
<given-names>JE</given-names>
</name>
<name><surname>Richie</surname>
<given-names>TL</given-names>
</name>
</person-group>
<article-title>The whole parasite, pre-erythrocytic stage approach to malaria vaccine development: a review</article-title>
<source>Curr Opin Infect Dis</source>
<year>2013</year>
<volume>26</volume>
<fpage>420</fpage>
<lpage>428</lpage>
<pub-id pub-id-type="pmid">23982233</pub-id>
</element-citation>
</ref>
<ref id="B138"><label>138</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hoffman</surname>
<given-names>SL</given-names>
</name>
<name><surname>Billingsley</surname>
<given-names>PF</given-names>
</name>
<name><surname>James</surname>
<given-names>E</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria</article-title>
<source>Hum Vaccin</source>
<year>2010</year>
<volume>6</volume>
<fpage>97</fpage>
<lpage>106</lpage>
<pub-id pub-id-type="pmid">19946222</pub-id>
</element-citation>
</ref>
<ref id="B139"><label>139</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Epstein</surname>
<given-names>JE</given-names>
</name>
<name><surname>Tewari</surname>
<given-names>K</given-names>
</name>
<name><surname>Lyke</surname>
<given-names>KE</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Live attenuated malaria vaccine designed to protect through hepatic CD8(+) T cell immunity</article-title>
<source>Science</source>
<year>2011</year>
<volume>334</volume>
<fpage>475</fpage>
<lpage>480</lpage>
<pub-id pub-id-type="pmid">21903775</pub-id>
</element-citation>
</ref>
<ref id="B140"><label>140</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Anassi</surname>
<given-names>E</given-names>
</name>
<name><surname>Ndefo</surname>
<given-names>UA</given-names>
</name>
</person-group>
<article-title>Sipuleucel-T (provenge) injection: the first immunotherapy agent (vaccine) for hormone-refractory prostate cancer</article-title>
<source>P T</source>
<year>2011</year>
<volume>36</volume>
<fpage>197</fpage>
<lpage>202</lpage>
<pub-id pub-id-type="pmid">21572775</pub-id>
</element-citation>
</ref>
<ref id="B141"><label>141</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Walls</surname>
<given-names>B</given-names>
</name>
<name><surname>Jordan</surname>
<given-names>L</given-names>
</name>
<name><surname>Diaz</surname>
<given-names>L</given-names>
</name>
<name><surname>Miller</surname>
<given-names>R</given-names>
</name>
</person-group>
<article-title>Targeted therapy for cutaneous oncology: a review of novel treatment options for non-melanoma skin cancer: part II</article-title>
<source>J Drugs Dermatol</source>
<year>2014</year>
<volume>13</volume>
<fpage>955</fpage>
<lpage>958</lpage>
<pub-id pub-id-type="pmid">25116974</pub-id>
</element-citation>
</ref>
<ref id="B142"><label>142</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Iacovelli</surname>
<given-names>R</given-names>
</name>
<name><surname>Pietrantonio</surname>
<given-names>F</given-names>
</name>
<name><surname>Farcomeni</surname>
<given-names>A</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Chemotherapy or targeted therapy as second-line treatment of advanced gastric cancer: a systematic review and meta-analysis of published studies</article-title>
<source>PLoS One</source>
<year>2014</year>
<volume>9</volume>
<fpage>e108940</fpage>
<pub-id pub-id-type="pmid">25268988</pub-id>
</element-citation>
</ref>
<ref id="B143"><label>143</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jansman</surname>
<given-names>FG</given-names>
</name>
<name><surname>Sleijfer</surname>
<given-names>DT</given-names>
</name>
<name><surname>de Graaf</surname>
<given-names>JC</given-names>
</name>
<name><surname>Coenen</surname>
<given-names>JL</given-names>
</name>
<name><surname>Brouwers</surname>
<given-names>JR</given-names>
</name>
</person-group>
<article-title>Management of chemotherapy-induced adverse effects in the treatment of colorectal cancer</article-title>
<source>Drug Saf</source>
<year>2001</year>
<volume>24</volume>
<fpage>353</fpage>
<lpage>367</lpage>
<pub-id pub-id-type="pmid">11419562</pub-id>
</element-citation>
</ref>
<ref id="B144"><label>144</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cortes</surname>
<given-names>J</given-names>
</name>
<name><surname>Calvo</surname>
<given-names>V</given-names>
</name>
<name><surname>Ramirez-Merino</surname>
<given-names>N</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Adverse events risk associated with bevacizumab addition to breast cancer chemotherapy: a meta-analysis</article-title>
<source>Ann Oncol</source>
<year>2012</year>
<volume>23</volume>
<fpage>1130</fpage>
<lpage>1137</lpage>
<pub-id pub-id-type="pmid">21976387</pub-id>
</element-citation>
</ref>
<ref id="B145"><label>145</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cartwright</surname>
<given-names>TH</given-names>
</name>
</person-group>
<article-title>Adverse events associated with antiangiogenic agents in combination with cytotoxic chemotherapy in metastatic colorectal cancer and their management</article-title>
<source>Clin Colorectal Cancer</source>
<year>2013</year>
<volume>12</volume>
<fpage>86</fpage>
<lpage>94</lpage>
<pub-id pub-id-type="pmid">23562587</pub-id>
</element-citation>
</ref>
<ref id="B146"><label>146</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thomay</surname>
<given-names>AA</given-names>
</name>
<name><surname>Nagorney</surname>
<given-names>DM</given-names>
</name>
<name><surname>Cohen</surname>
<given-names>SJ</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Modern chemotherapy mitigates adverse prognostic effect of regional nodal metastases in stage IV colorectal cancer</article-title>
<source>J Gastrointest Surg</source>
<year>2014</year>
<volume>18</volume>
<fpage>69</fpage>
<lpage>74</lpage>
<pub-id pub-id-type="pmid">24002765</pub-id>
</element-citation>
</ref>
<ref id="B147"><label>147</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Peng</surname>
<given-names>SL</given-names>
</name>
<name><surname>Thomas</surname>
<given-names>M</given-names>
</name>
<name><surname>Ruszkiewicz</surname>
<given-names>A</given-names>
</name>
<name><surname>Hunter</surname>
<given-names>A</given-names>
</name>
<name><surname>Lawrence</surname>
<given-names>M</given-names>
</name>
<name><surname>Moore</surname>
<given-names>J</given-names>
</name>
</person-group>
<article-title>Conventional adverse features do not predict response to adjuvant chemotherapy in stage II colon cancer</article-title>
<source>ANZ J Surg</source>
<year>2014</year>
<volume>84</volume>
<fpage>837</fpage>
<lpage>841</lpage>
<pub-id pub-id-type="pmid">24224835</pub-id>
</element-citation>
</ref>
<ref id="B148"><label>148</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Duncan</surname>
<given-names>W</given-names>
</name>
<name><surname>MacDougall</surname>
<given-names>RH</given-names>
</name>
<name><surname>Kerr</surname>
<given-names>GR</given-names>
</name>
<name><surname>Downing</surname>
<given-names>D</given-names>
</name>
</person-group>
<article-title>Adverse effect of treatment gaps in the outcome of radiotherapy for laryngeal cancer</article-title>
<source>Radiother Oncol</source>
<year>1996</year>
<volume>41</volume>
<fpage>203</fpage>
<lpage>207</lpage>
<pub-id pub-id-type="pmid">9027934</pub-id>
</element-citation>
</ref>
<ref id="B149"><label>149</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rades</surname>
<given-names>D</given-names>
</name>
<name><surname>Fehlauer</surname>
<given-names>F</given-names>
</name>
<name><surname>Bajrovic</surname>
<given-names>A</given-names>
</name>
<name><surname>Mahlmann</surname>
<given-names>B</given-names>
</name>
<name><surname>Richter</surname>
<given-names>E</given-names>
</name>
<name><surname>Alberti</surname>
<given-names>W</given-names>
</name>
</person-group>
<article-title>Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients</article-title>
<source>Radiother Oncol</source>
<year>2004</year>
<volume>70</volume>
<fpage>261</fpage>
<lpage>264</lpage>
<pub-id pub-id-type="pmid">15064010</pub-id>
</element-citation>
</ref>
<ref id="B150"><label>150</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kerns</surname>
<given-names>SL</given-names>
</name>
<name><surname>Ostrer</surname>
<given-names>H</given-names>
</name>
<name><surname>Rosenstein</surname>
<given-names>BS</given-names>
</name>
</person-group>
<article-title>Radiogenomics: using genetics to identify cancer patients at risk for development of adverse effects following radiotherapy</article-title>
<source>Cancer Discov</source>
<year>2014</year>
<volume>4</volume>
<fpage>155</fpage>
<lpage>165</lpage>
<pub-id pub-id-type="pmid">24441285</pub-id>
</element-citation>
</ref>
<ref id="B151"><label>151</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Palucka</surname>
<given-names>K</given-names>
</name>
<name><surname>Banchereau</surname>
<given-names>J</given-names>
</name>
</person-group>
<article-title>Cancer immunotherapy via dendritic cells</article-title>
<source>Nat Rev Cancer</source>
<year>2012</year>
<volume>12</volume>
<fpage>265</fpage>
<lpage>277</lpage>
<pub-id pub-id-type="pmid">22437871</pub-id>
</element-citation>
</ref>
<ref id="B152"><label>152</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Patel</surname>
<given-names>PH</given-names>
</name>
<name><surname>Kockler</surname>
<given-names>DR</given-names>
</name>
</person-group>
<article-title>Sipuleucel-T: a vaccine for metastatic, asymptomatic, androgen-independent prostate cancer</article-title>
<source>Ann Pharmacother</source>
<year>2008</year>
<volume>42</volume>
<fpage>91</fpage>
<lpage>98</lpage>
<pub-id pub-id-type="pmid">18094343</pub-id>
</element-citation>
</ref>
<ref id="B153"><label>153</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Small</surname>
<given-names>EJ</given-names>
</name>
<name><surname>Schellhammer</surname>
<given-names>PF</given-names>
</name>
<name><surname>Higano</surname>
<given-names>CS</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer</article-title>
<source>J Clin Oncol</source>
<year>2006</year>
<volume>24</volume>
<fpage>3089</fpage>
<lpage>3094</lpage>
<pub-id pub-id-type="pmid">16809734</pub-id>
</element-citation>
</ref>
<ref id="B154"><label>154</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kantoff</surname>
<given-names>PW</given-names>
</name>
<name><surname>Higano</surname>
<given-names>CS</given-names>
</name>
<name><surname>Shore</surname>
<given-names>ND</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Sipuleucel-T immunotherapy for castration-resistant prostate cancer</article-title>
<source>N Engl J Med</source>
<year>2010</year>
<volume>363</volume>
<fpage>411</fpage>
<lpage>422</lpage>
<pub-id pub-id-type="pmid">20818862</pub-id>
</element-citation>
</ref>
<ref id="B155"><label>155</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nemunaitis</surname>
<given-names>J</given-names>
</name>
</person-group>
<article-title>Vaccines in cancer: GVAX, a GM-CSF gene vaccine</article-title>
<source>Expert Rev Vaccines</source>
<year>2005</year>
<volume>4</volume>
<fpage>259</fpage>
<lpage>274</lpage>
<pub-id pub-id-type="pmid">16026242</pub-id>
</element-citation>
</ref>
<ref id="B156"><label>156</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dummer</surname>
<given-names>R</given-names>
</name>
</person-group>
<article-title>GVAX (Cell Genesys)</article-title>
<source>Curr Opin Investig Drugs</source>
<year>2001</year>
<volume>2</volume>
<fpage>844</fpage>
<lpage>848</lpage>
</element-citation>
</ref>
<ref id="B157"><label>157</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Geary</surname>
<given-names>SM</given-names>
</name>
<name><surname>Lemke</surname>
<given-names>CD</given-names>
</name>
<name><surname>Lubaroff</surname>
<given-names>DM</given-names>
</name>
<name><surname>Salem</surname>
<given-names>AK</given-names>
</name>
</person-group>
<article-title>Proposed mechanisms of action for prostate cancer vaccines</article-title>
<source>Nat Rev Urol</source>
<year>2013</year>
<volume>10</volume>
<fpage>149</fpage>
<lpage>160</lpage>
<pub-id pub-id-type="pmid">23399727</pub-id>
</element-citation>
</ref>
<ref id="B158"><label>158</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Callahan</surname>
<given-names>MK</given-names>
</name>
<name><surname>Wolchok</surname>
<given-names>JD</given-names>
</name>
</person-group>
<article-title>At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy</article-title>
<source>J Leukoc Biol</source>
<year>2013</year>
<volume>94</volume>
<fpage>41</fpage>
<lpage>53</lpage>
<pub-id pub-id-type="pmid">23667165</pub-id>
</element-citation>
</ref>
</ref-list>
</back>
<floats-group><fig id="F1" orientation="portrait" position="float"><label>Fig. 1</label>
<caption><p>Irradiated pneumococcal vaccine induced antibody titers. Irradiated or formalin-treated vaccines were administered intranasally to CD-1 mice (n = 5) with phosphate buffered saline (PBS), cholera toxin (CT), or lipid A at days 0 and 14. Pneumococcal specific immunoglobulin A in bronchoalveolar lavage fluid (BALF) (A) and total immunoglobulin (B) were measured at 5 days after final immunization.</p>
</caption>
<graphic xlink:href="cevr-4-145-g001"></graphic>
</fig>
<table-wrap id="T1" orientation="portrait" position="float"><label>Table 1</label>
<caption><p>Summary of irradiated bacterial vaccines</p>
</caption>
<alternatives><graphic xlink:href="cevr-4-145-i001"></graphic>
<table frame="hsides" rules="rows"><thead><tr><th valign="middle" align="left" rowspan="1" colspan="1">Bacteria</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Vaccine efficacy</th>
<th valign="middle" align="center" rowspan="1" colspan="1">References</th>
</tr>
</thead>
<tbody><tr><td valign="top" align="left" rowspan="1" colspan="1">Gram negative bacteria</td>
<td valign="top" align="left" rowspan="1" colspan="1"></td>
<td valign="top" align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1"> <italic>Mycobacteria lepae</italic>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">Reduce <italic>M. leprae</italic>
by boosting vaccination with irradiated <italic>M. leprae</italic>
vaccine in a human study</td>
<td valign="top" align="center" rowspan="1" colspan="1">[<xref rid="B75" ref-type="bibr">75</xref>
<xref rid="B76" ref-type="bibr">76</xref>
]</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1"> <italic>M. avium</italic>
subsp. <italic>paratuberculosis</italic>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">Irradiated mycobacteria vaccine elicits a similar level of protection with live <italic>M. bovis </italic>
BCG vaccine in both mouse and human models</td>
<td valign="top" align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1"> Bacillus Calmette-Guerin</td>
<td valign="top" align="left" rowspan="1" colspan="1">Elicits both CD4- and CD8-specific immune responses in mouse, cow, and chicken models</td>
<td valign="top" align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1"> <italic>Salmonella typhimurium</italic>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">Induce antigen-specific antibody and T-cell responses</td>
<td valign="top" align="center" rowspan="1" colspan="1">[<xref rid="B40" ref-type="bibr">40</xref>
<xref rid="B77" ref-type="bibr">77</xref>
]</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1"> <italic>Brucella neotomae</italic>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">Protect <italic>B. abortus, B. melitensis</italic>
, and <italic>B. suis </italic>
infections in a mouse model</td>
<td valign="top" align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1"> <italic>Brucella melitensis</italic>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">Induces mucosal immune response without adjuvant</td>
<td valign="top" align="center" rowspan="1" colspan="1">[<xref rid="B78" ref-type="bibr">78</xref>
<xref rid="B79" ref-type="bibr">79</xref>
<xref rid="B80" ref-type="bibr">80</xref>
]</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1"> <italic>Vibrio cholera</italic>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">Prevents <italic>V. cholera </italic>
colonization and toxin neutralization</td>
<td valign="top" align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">Gram positive bacteria</td>
<td valign="top" align="left" rowspan="1" colspan="1"></td>
<td valign="top" align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td valign="top" align="left" rowspan="3" colspan="1"> <italic>Streptococcus agalactiae</italic>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">Does not cause inflammation of the mammary glands of mice</td>
<td valign="top" align="center" rowspan="3" colspan="1">[<xref rid="B81" ref-type="bibr">81</xref>
<xref rid="B82" ref-type="bibr">82</xref>
<xref rid="B83" ref-type="bibr">83</xref>
]</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">Elicits GBS antibody response in mice</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">Partial protection against Nile Tilapia</td>
</tr>
<tr><td valign="top" align="left" rowspan="2" colspan="1"> <italic>Staphylococcus aureus</italic>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">Elicits anti-<italic>S. aureus </italic>
specific antibodies</td>
<td valign="top" align="center" rowspan="2" colspan="1">[<xref rid="B84" ref-type="bibr">84</xref>
<xref rid="B85" ref-type="bibr">85</xref>
<xref rid="B86" ref-type="bibr">86</xref>
]</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">Reduces <italic>S. aureus</italic>
colonization in the kidneys and skin</td>
</tr>
<tr><td valign="top" align="left" rowspan="2" colspan="1"> <italic>Listeria monocytogens</italic>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">Provides higher protection against a <italic>Listeria</italic>
challenge model than heat and chemically killed vaccine</td>
<td valign="top" align="center" rowspan="2" colspan="1">[<xref rid="B39" ref-type="bibr">39</xref>
]</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">Elicits an effective and specific CD8+ T-cell response</td>
</tr>
</tbody>
</table>
</alternatives>
<table-wrap-foot><fn><p>BCG, bacille Calmette-Guerin; GBS, Group B Streptococci.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="T2" orientation="portrait" position="float"><label>Table 2</label>
<caption><p>Clinical trials of the GVAX vaccine</p>
</caption>
<alternatives><graphic xlink:href="cevr-4-145-i002"></graphic>
<table frame="hsides" rules="rows"><thead><tr><th valign="middle" align="left" rowspan="1" colspan="1">Trial code</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Status</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Sponsor</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Conditions</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Features</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Combination</th>
</tr>
</thead>
<tbody><tr><td valign="top" align="left" rowspan="1" colspan="1">NCT00140400</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase III</td>
<td valign="top" align="left" rowspan="1" colspan="1">Cell Genesys Inc.</td>
<td valign="top" align="left" rowspan="1" colspan="1">Metastatic hormone-refractory prostate cancer</td>
<td valign="top" align="left" rowspan="1" colspan="1">Non-patient specific</td>
<td valign="top" align="left" rowspan="1" colspan="1">Docetaxel and Prednisone</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">NCT00133224</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase III</td>
<td valign="top" align="left" rowspan="1" colspan="1">Cell Genesys Inc.</td>
<td valign="top" align="left" rowspan="1" colspan="1">Metastatic hormone-refractory prostate cancer with pain</td>
<td valign="top" align="left" rowspan="1" colspan="1">Non-patient specific</td>
<td valign="top" align="left" rowspan="1" colspan="1">Docetaxel and Prednisone</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">NCT00089726</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II</td>
<td valign="top" align="left" rowspan="1" colspan="1">Cell Genesys Inc.</td>
<td valign="top" align="left" rowspan="1" colspan="1">Advanced stage non-small-cell lung cancer</td>
<td valign="top" align="left" rowspan="1" colspan="1">Patient-specific</td>
<td valign="top" align="left" rowspan="1" colspan="1">Cyclophosphamide</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">NCT00084383</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II</td>
<td valign="top" align="left" rowspan="1" colspan="1">Sidney Kimmel Comprehensive Cancer Center</td>
<td valign="top" align="left" rowspan="1" colspan="1">Resectable pancreatic cancer</td>
<td valign="top" align="left" rowspan="1" colspan="1">Non-patient specific</td>
<td valign="top" align="left" rowspan="1" colspan="1">Nil</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">NCT00116467</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II</td>
<td valign="top" align="left" rowspan="1" colspan="1">Cell Genesys Inc.</td>
<td valign="top" align="left" rowspan="1" colspan="1">Acute myelogenous leukemia</td>
<td valign="top" align="left" rowspan="1" colspan="1">Patient-specific</td>
<td valign="top" align="left" rowspan="1" colspan="1">Nil</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">NCT00116441</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II</td>
<td valign="top" align="left" rowspan="1" colspan="1">Cell Genesys Inc.</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multiple myeloma</td>
<td valign="top" align="left" rowspan="1" colspan="1">Patient-specific</td>
<td valign="top" align="left" rowspan="1" colspan="1">Nil</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">NCT00656123</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase I</td>
<td valign="top" align="left" rowspan="1" colspan="1">Sidney Kimmel Comprehensive Cancer Center</td>
<td valign="top" align="left" rowspan="1" colspan="1">Colorectal cancer</td>
<td valign="top" align="left" rowspan="1" colspan="1">Non-patient specific</td>
<td valign="top" align="left" rowspan="1" colspan="1">Cyclophosphamide</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">NCT00836407</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase I</td>
<td valign="top" align="left" rowspan="1" colspan="1">Sidney Kimmel Comprehensive Cancer Center</td>
<td valign="top" align="left" rowspan="1" colspan="1">Pancreatic cancer</td>
<td valign="top" align="left" rowspan="1" colspan="1">Non-patient specific</td>
<td valign="top" align="left" rowspan="1" colspan="1">Ipilimumab</td>
</tr>
<tr><td valign="top" align="left" rowspan="1" colspan="1">NCT01510288</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase I</td>
<td valign="top" align="left" rowspan="1" colspan="1">VU University Medical Center</td>
<td valign="top" align="left" rowspan="1" colspan="1">Prostate cancer</td>
<td valign="top" align="left" rowspan="1" colspan="1">Non-patient specific</td>
<td valign="top" align="left" rowspan="1" colspan="1">Ipilimumab</td>
</tr>
</tbody>
</table>
</alternatives>
</table-wrap>
</floats-group>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000506 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000506 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= LymphedemaV1 |flux= Pmc |étape= Corpus |type= RBID |clé= PMC:4524899 |texte= Application of radiation technology in vaccines development }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:26273573" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \ | NlmPubMed2Wicri -a LymphedemaV1
![]() | This area was generated with Dilib version V0.6.31. | ![]() |