A vaccine consisting of Schistosoma mansoni cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis
Identifieur interne : 000094 ( Pmc/Curation ); précédent : 000093; suivant : 000095A vaccine consisting of Schistosoma mansoni cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis
Auteurs : Alessandra Ricciardi [Canada] ; Kittipos Visitsunthorn [Canada] ; John P. Dalton [Canada, Royaume-Uni] ; Momar Ndao [Canada]Source :
- BMC Infectious Diseases [ 1471-2334 ] ; 2016.
Abstract
Schistosomiasis is the most important human helminth infection due to its impact on public health. The clinical manifestations are chronic and significantly decrease an individual’s quality of life. Infected individuals suffer from long-term organ pathologies including fibrosis which eventually leads to organ failure. The development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission.
Our group has chosen
The Sm-cathepsin B and Montanide formulation conferred protection against a challenge infection by significantly reducing all forms of parasitological burdens. Worm burden, hepatic egg burden and intestinal egg burden were decreased by 60 %, 62 %, and 56 %, respectively in immunized animals compared to controls (
The formulation tested in this study was able to significantly reduce all forms of parasite burden, stimulate robust production of antigen-specific antibodies, and induce a mixed Th1/Th2 response. These results highlight the potential of Sm-cathepsin B/Montanide ISA 720 VG as a vaccine candidate against schistosomiasis.
The online version of this article (doi:10.1186/s12879-016-1444-z) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12879-016-1444-z
PubMed: 26945988
PubMed Central: 4779570
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000095
Links to Exploration step
PMC:4779570Curation
No country items
Alessandra Ricciardi<affiliation><nlm:aff id="Aff4">National Reference Center for Parasitology, Research Institute of the McGill University Health Center, Montreal, QC Canada</nlm:aff>
<wicri:noCountry code="subfield">QC Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff4">National Reference Center for Parasitology, Research Institute of the McGill University Health Center, Montreal, QC Canada</nlm:aff>
<wicri:noCountry code="subfield">QC Canada</wicri:noCountry>
</affiliation>
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A vaccine consisting of <italic>Schistosoma mansoni</italic>
cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis</title>
<author><name sortKey="Ricciardi, Alessandra" sort="Ricciardi, Alessandra" uniqKey="Ricciardi A" first="Alessandra" last="Ricciardi">Alessandra Ricciardi</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</nlm:aff>
<orgName type="university">Université McGill</orgName>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="Aff4">National Reference Center for Parasitology, Research Institute of the McGill University Health Center, Montreal, QC Canada</nlm:aff>
<wicri:noCountry code="subfield">QC Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Visitsunthorn, Kittipos" sort="Visitsunthorn, Kittipos" uniqKey="Visitsunthorn K" first="Kittipos" last="Visitsunthorn">Kittipos Visitsunthorn</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</nlm:aff>
<orgName type="university">Université McGill</orgName>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dalton, John P" sort="Dalton, John P" uniqKey="Dalton J" first="John P." last="Dalton">John P. Dalton</name>
<affiliation wicri:level="4"><nlm:aff id="Aff2">Institute of Parasitology, McGill University, Montreal, QC Canada</nlm:aff>
<orgName type="university">Université McGill</orgName>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff3">School of Biological Sciences, Medical Biology Centre (MBC) Queen’s University Belfast, Belfast, Northern Ireland</nlm:aff>
<country>Royaume-Uni</country>
<placeName><region type="country">Irlande du Nord</region>
</placeName>
<wicri:cityArea>School of Biological Sciences, Medical Biology Centre (MBC) Queen’s University Belfast, Belfast</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Ndao, Momar" sort="Ndao, Momar" uniqKey="Ndao M" first="Momar" last="Ndao">Momar Ndao</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</nlm:aff>
<orgName type="university">Université McGill</orgName>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="Aff4">National Reference Center for Parasitology, Research Institute of the McGill University Health Center, Montreal, QC Canada</nlm:aff>
<wicri:noCountry code="subfield">QC Canada</wicri:noCountry>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">26945988</idno>
<idno type="pmc">4779570</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779570</idno>
<idno type="RBID">PMC:4779570</idno>
<idno type="doi">10.1186/s12879-016-1444-z</idno>
<date when="2016">2016</date>
<idno type="wicri:Area/Pmc/Corpus">000095</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000095</idno>
<idno type="wicri:Area/Pmc/Curation">000094</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000094</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A vaccine consisting of <italic>Schistosoma mansoni</italic>
cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis</title>
<author><name sortKey="Ricciardi, Alessandra" sort="Ricciardi, Alessandra" uniqKey="Ricciardi A" first="Alessandra" last="Ricciardi">Alessandra Ricciardi</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</nlm:aff>
<orgName type="university">Université McGill</orgName>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="Aff4">National Reference Center for Parasitology, Research Institute of the McGill University Health Center, Montreal, QC Canada</nlm:aff>
<wicri:noCountry code="subfield">QC Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Visitsunthorn, Kittipos" sort="Visitsunthorn, Kittipos" uniqKey="Visitsunthorn K" first="Kittipos" last="Visitsunthorn">Kittipos Visitsunthorn</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</nlm:aff>
<orgName type="university">Université McGill</orgName>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dalton, John P" sort="Dalton, John P" uniqKey="Dalton J" first="John P." last="Dalton">John P. Dalton</name>
<affiliation wicri:level="4"><nlm:aff id="Aff2">Institute of Parasitology, McGill University, Montreal, QC Canada</nlm:aff>
<orgName type="university">Université McGill</orgName>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff3">School of Biological Sciences, Medical Biology Centre (MBC) Queen’s University Belfast, Belfast, Northern Ireland</nlm:aff>
<country>Royaume-Uni</country>
<placeName><region type="country">Irlande du Nord</region>
</placeName>
<wicri:cityArea>School of Biological Sciences, Medical Biology Centre (MBC) Queen’s University Belfast, Belfast</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Ndao, Momar" sort="Ndao, Momar" uniqKey="Ndao M" first="Momar" last="Ndao">Momar Ndao</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</nlm:aff>
<orgName type="university">Université McGill</orgName>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="Aff4">National Reference Center for Parasitology, Research Institute of the McGill University Health Center, Montreal, QC Canada</nlm:aff>
<wicri:noCountry code="subfield">QC Canada</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series><title level="j">BMC Infectious Diseases</title>
<idno type="eISSN">1471-2334</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Schistosomiasis is the most important human helminth infection due to its impact on public health. The clinical manifestations are chronic and significantly decrease an individual’s quality of life. Infected individuals suffer from long-term organ pathologies including fibrosis which eventually leads to organ failure. The development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission.</p>
</sec>
<sec><title>Method</title>
<p>Our group has chosen <italic>Schistosoma mansoni</italic>
(Sm) cathepsin B, a peptidase involved in parasite feeding, as a prospective vaccine candidate. Our experimental formulation consisted of recombinant Sm-cathepsin B formulated in Montanide ISA 720 VG, a squalene based adjuvant containing a mannide mono-oleate emulsifier. Parasitological burden was assessed by determining adult worm, hepatic egg, and intestinal egg numbers in each mouse. Serum was used in ELISAs to evaluate production of antigen-specific antibodies, and isolated splenocytes were stimulated with the antigen for the analysis of cytokine secretion levels.</p>
</sec>
<sec><title>Results</title>
<p>The Sm-cathepsin B and Montanide formulation conferred protection against a challenge infection by significantly reducing all forms of parasitological burdens. Worm burden, hepatic egg burden and intestinal egg burden were decreased by 60 %, 62 %, and 56 %, respectively in immunized animals compared to controls (<italic>P</italic>
= 0.0002, <italic>P</italic>
< 0.0001, <italic>P</italic>
= 0.0009, respectively). Immunizations with the vaccine elicited robust production of Sm-cathepsin B specific antibodies (endpoint titers = 122,880). Both antigen-specific IgG1 and IgG2c titers were observed, with the former having more elevated titers. Furthermore, splenocytes isolated from the immunized animals, compared to control animals, secreted higher levels of key Th1 cytokines, IFN-γ, IL-12, and TNF-α, as well as the Th2 cytokines IL-5 and IL-4 when stimulated with recombinant Sm-cathepsin B. The Th17 cytokine IL-17, the chemokine CCL5, and the growth factor GM-CSF were also significantly increased in the immunized animals compared to the controls.</p>
</sec>
<sec><title>Conclusion</title>
<p>The formulation tested in this study was able to significantly reduce all forms of parasite burden, stimulate robust production of antigen-specific antibodies, and induce a mixed Th1/Th2 response. These results highlight the potential of Sm-cathepsin B/Montanide ISA 720 VG as a vaccine candidate against schistosomiasis.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s12879-016-1444-z) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Chitsulo, L" uniqKey="Chitsulo L">L Chitsulo</name>
</author>
<author><name sortKey="Engels, D" uniqKey="Engels D">D Engels</name>
</author>
<author><name sortKey="Montresor, A" uniqKey="Montresor A">A Montresor</name>
</author>
<author><name sortKey="Saviolo, L" uniqKey="Saviolo L">L Saviolo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gryseels, B" uniqKey="Gryseels B">B Gryseels</name>
</author>
<author><name sortKey="Polman, K" uniqKey="Polman K">K Polman</name>
</author>
<author><name sortKey="Clerinx, J" uniqKey="Clerinx J">J Clerinx</name>
</author>
<author><name sortKey="Kestens, L" uniqKey="Kestens L">L Kestens</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hotez, Pj" uniqKey="Hotez P">PJ Hotez</name>
</author>
<author><name sortKey="Fenwick, A" uniqKey="Fenwick A">A Fenwick</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="King, Ch" uniqKey="King C">CH King</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="King, Ch" uniqKey="King C">CH King</name>
</author>
<author><name sortKey="Dangerfield Cha, M" uniqKey="Dangerfield Cha M">M Dangerfield-Cha</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Terer, Cc" uniqKey="Terer C">CC Terer</name>
</author>
<author><name sortKey="Bustinduy, Al" uniqKey="Bustinduy A">AL Bustinduy</name>
</author>
<author><name sortKey="Magtanong, Rv" uniqKey="Magtanong R">RV Magtanong</name>
</author>
<author><name sortKey="Muhoho, N" uniqKey="Muhoho N">N Muhoho</name>
</author>
<author><name sortKey="Mungai, Pl" uniqKey="Mungai P">PL Mungai</name>
</author>
<author><name sortKey="Muchiri, Em" uniqKey="Muchiri E">EM Muchiri</name>
</author>
<author><name sortKey="Kitron, Ch" uniqKey="Kitron C">CH Kitron</name>
</author>
<author><name sortKey="King, Ch" uniqKey="King C">CH King</name>
</author>
<author><name sortKey="Mutuku, Fm" uniqKey="Mutuku F">FM Mutuku</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Rollinson, D" uniqKey="Rollinson D">D Rollinson</name>
</author>
<author><name sortKey="Knopp, S" uniqKey="Knopp S">S Knopp</name>
</author>
<author><name sortKey="Levitz, S" uniqKey="Levitz S">S Levitz</name>
</author>
<author><name sortKey="Stothard, Jr" uniqKey="Stothard J">JR Stothard</name>
</author>
<author><name sortKey="Tchuem Tchuente, La" uniqKey="Tchuem Tchuente L">LA Tchuem Tchuenté</name>
</author>
<author><name sortKey="Garba, A" uniqKey="Garba A">A Garba</name>
</author>
<author><name sortKey="Mohammed, Ka" uniqKey="Mohammed K">KA Mohammed</name>
</author>
<author><name sortKey="Schur, N" uniqKey="Schur N">N Schur</name>
</author>
<author><name sortKey="Person, B" uniqKey="Person B">B Person</name>
</author>
<author><name sortKey="Colley, Dg" uniqKey="Colley D">DG Colley</name>
</author>
<author><name sortKey="Utzinger, J" uniqKey="Utzinger J">J Utzinger</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hotez, Pj" uniqKey="Hotez P">PJ Hotez</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="King, Ch" uniqKey="King C">CH King</name>
</author>
<author><name sortKey="Olbrych, Sk" uniqKey="Olbrych S">SK Olbrych</name>
</author>
<author><name sortKey="Soon, M" uniqKey="Soon M">M Soon</name>
</author>
<author><name sortKey="Singer, Me" uniqKey="Singer M">ME Singer</name>
</author>
<author><name sortKey="Carter, J" uniqKey="Carter J">J Carter</name>
</author>
<author><name sortKey="Colley, Dg" uniqKey="Colley D">DG Colley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bergquist, Nr" uniqKey="Bergquist N">NR Bergquist</name>
</author>
<author><name sortKey="Leonardo, Lr" uniqKey="Leonardo L">LR Leonardo</name>
</author>
<author><name sortKey="Mitchell, Gf" uniqKey="Mitchell G">GF Mitchell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bergquist, R" uniqKey="Bergquist R">R Bergquist</name>
</author>
<author><name sortKey="Utzinger, J" uniqKey="Utzinger J">J Utzinger</name>
</author>
<author><name sortKey="Mcmanus, Dp" uniqKey="Mcmanus D">DP McManus</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Klinkert, Mq" uniqKey="Klinkert M">MQ Klinkert</name>
</author>
<author><name sortKey="Ruppel, A" uniqKey="Ruppel A">A Ruppel</name>
</author>
<author><name sortKey="Beck, E" uniqKey="Beck E">E Beck</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Klinkert, Mq" uniqKey="Klinkert M">MQ Klinkert</name>
</author>
<author><name sortKey="Felleisen, R" uniqKey="Felleisen R">R Felleisen</name>
</author>
<author><name sortKey="Link, G" uniqKey="Link G">G Link</name>
</author>
<author><name sortKey="Ruppel, A" uniqKey="Ruppel A">A Ruppel</name>
</author>
<author><name sortKey="Beck, E" uniqKey="Beck E">E Beck</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Brindley, Pj" uniqKey="Brindley P">PJ Brindley</name>
</author>
<author><name sortKey="Kalinna, Bh" uniqKey="Kalinna B">BH Kalinna</name>
</author>
<author><name sortKey="Dalton, Jp" uniqKey="Dalton J">JP Dalton</name>
</author>
<author><name sortKey="Day, Sr" uniqKey="Day S">SR Day</name>
</author>
<author><name sortKey="Wong, Jy" uniqKey="Wong J">JY Wong</name>
</author>
<author><name sortKey="Smythe, Ml" uniqKey="Smythe M">ML Smythe</name>
</author>
<author><name sortKey="Mcmanus, Dp" uniqKey="Mcmanus D">DP McManus</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Caffrey, Cr" uniqKey="Caffrey C">CR Caffrey</name>
</author>
<author><name sortKey="Mckerrow, Jh" uniqKey="Mckerrow J">JH McKerrow</name>
</author>
<author><name sortKey="Salter, Jp" uniqKey="Salter J">JP Salter</name>
</author>
<author><name sortKey="Sajid, M" uniqKey="Sajid M">M Sajid</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Delcroix, M" uniqKey="Delcroix M">M Delcroix</name>
</author>
<author><name sortKey="Sajid, M" uniqKey="Sajid M">M Sajid</name>
</author>
<author><name sortKey="Caffrey, Cr" uniqKey="Caffrey C">CR Caffrey</name>
</author>
<author><name sortKey="Lim, Kc" uniqKey="Lim K">KC Lim</name>
</author>
<author><name sortKey="Dvorak, J" uniqKey="Dvorak J">J Dvorák</name>
</author>
<author><name sortKey="Hsieh, I" uniqKey="Hsieh I">I Hsieh</name>
</author>
<author><name sortKey="Bahgat, M" uniqKey="Bahgat M">M Bahgat</name>
</author>
<author><name sortKey="Dissous, C" uniqKey="Dissous C">C Dissous</name>
</author>
<author><name sortKey="Mckerrow, Jh" uniqKey="Mckerrow J">JH McKerrow</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Delcroix, M" uniqKey="Delcroix M">M Delcroix</name>
</author>
<author><name sortKey="Medzihradsky, K" uniqKey="Medzihradsky K">K Medzihradsky</name>
</author>
<author><name sortKey="Caffrey, Cr" uniqKey="Caffrey C">CR Caffrey</name>
</author>
<author><name sortKey="Fetter, Rd" uniqKey="Fetter R">RD Fetter</name>
</author>
<author><name sortKey="Mckerrow, Jh" uniqKey="Mckerrow J">JH McKerrow</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sajid, M" uniqKey="Sajid M">M Sajid</name>
</author>
<author><name sortKey="Mckerrow, Jh" uniqKey="Mckerrow J">JH McKerrow</name>
</author>
<author><name sortKey="Hansell, E" uniqKey="Hansell E">E Hansell</name>
</author>
<author><name sortKey="Mathieu, Ma" uniqKey="Mathieu M">MA Mathieu</name>
</author>
<author><name sortKey="Lucas, Kd" uniqKey="Lucas K">KD Lucas</name>
</author>
<author><name sortKey="Hsieh, I" uniqKey="Hsieh I">I Hsieh</name>
</author>
<author><name sortKey="Greenbaum, D" uniqKey="Greenbaum D">D Greenbaum</name>
</author>
<author><name sortKey="Bogyo, M" uniqKey="Bogyo M">M Bogyo</name>
</author>
<author><name sortKey="Salter, Jp" uniqKey="Salter J">JP Salter</name>
</author>
<author><name sortKey="Lim, Kc" uniqKey="Lim K">KC Lim</name>
</author>
<author><name sortKey="Franklin, C" uniqKey="Franklin C">C Franklin</name>
</author>
<author><name sortKey="Kim, Jh" uniqKey="Kim J">JH Kim</name>
</author>
<author><name sortKey="Caffrey, Cr" uniqKey="Caffrey C">CR Caffrey</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Correnti, Jm" uniqKey="Correnti J">JM Correnti</name>
</author>
<author><name sortKey="Brindley, Pj" uniqKey="Brindley P">PJ Brindley</name>
</author>
<author><name sortKey="Pearce, Ej" uniqKey="Pearce E">EJ Pearce</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Remarque, Ej" uniqKey="Remarque E">EJ Remarque</name>
</author>
<author><name sortKey="Roestenberg, M" uniqKey="Roestenberg M">M Roestenberg</name>
</author>
<author><name sortKey="Younis, S" uniqKey="Younis S">S Younis</name>
</author>
<author><name sortKey="Walraven, V" uniqKey="Walraven V">V Walraven</name>
</author>
<author><name sortKey="Van Der Werff, N" uniqKey="Van Der Werff N">N van der Werff</name>
</author>
<author><name sortKey="Faber, Bw" uniqKey="Faber B">BW Faber</name>
</author>
<author><name sortKey="Leroy, O" uniqKey="Leroy O">O Leroy</name>
</author>
<author><name sortKey="Sauerwein, R" uniqKey="Sauerwein R">R Sauerwein</name>
</author>
<author><name sortKey="Kocken, Ch" uniqKey="Kocken C">CH Kocken</name>
</author>
<author><name sortKey="Thomas, Aw" uniqKey="Thomas A">AW Thomas</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Uttenthal, B" uniqKey="Uttenthal B">B Uttenthal</name>
</author>
<author><name sortKey="Martinez Davila, I" uniqKey="Martinez Davila I">I Martinez-Davila</name>
</author>
<author><name sortKey="Ivey, A" uniqKey="Ivey A">A Ivey</name>
</author>
<author><name sortKey="Craddock, C" uniqKey="Craddock C">C Craddock</name>
</author>
<author><name sortKey="Chen, F" uniqKey="Chen F">F Chen</name>
</author>
<author><name sortKey="Virchis, A" uniqKey="Virchis A">A Virchis</name>
</author>
<author><name sortKey="Kottaridis, P" uniqKey="Kottaridis P">P Kottaridis</name>
</author>
<author><name sortKey="Grimwade, D" uniqKey="Grimwade D">D Grimwade</name>
</author>
<author><name sortKey="Khwaja, A" uniqKey="Khwaja A">A Khwaja</name>
</author>
<author><name sortKey="Stauss, H" uniqKey="Stauss H">H Stauss</name>
</author>
<author><name sortKey="Morris, Ec" uniqKey="Morris E">EC Morris</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Toledo, H" uniqKey="Toledo H">H Toledo</name>
</author>
<author><name sortKey="Baly, A" uniqKey="Baly A">A Baly</name>
</author>
<author><name sortKey="Castro, O" uniqKey="Castro O">O Castro</name>
</author>
<author><name sortKey="Resik, S" uniqKey="Resik S">S Resik</name>
</author>
<author><name sortKey="Laferte, J" uniqKey="Laferte J">J Laferté</name>
</author>
<author><name sortKey="Rolo, F" uniqKey="Rolo F">F Rolo</name>
</author>
<author><name sortKey="Navea, L" uniqKey="Navea L">L Navea</name>
</author>
<author><name sortKey="Lobaina, L" uniqKey="Lobaina L">L Lobaina</name>
</author>
<author><name sortKey="Cruz, O" uniqKey="Cruz O">O Cruz</name>
</author>
<author><name sortKey="Miguez, J" uniqKey="Miguez J">J Miguez</name>
</author>
<author><name sortKey="Serrano, T" uniqKey="Serrano T">T Serrano</name>
</author>
<author><name sortKey="Sierra, B" uniqKey="Sierra B">B Sierra</name>
</author>
<author><name sortKey="Perez, L" uniqKey="Perez L">L Pérez</name>
</author>
<author><name sortKey="Ricardo, Me" uniqKey="Ricardo M">ME Ricardo</name>
</author>
<author><name sortKey="Dubed, M" uniqKey="Dubed M">M Dubed</name>
</author>
<author><name sortKey="Lubian, Al" uniqKey="Lubian A">AL Lubián</name>
</author>
<author><name sortKey="Blanco, M" uniqKey="Blanco M">M Blanco</name>
</author>
<author><name sortKey="Millan, Jc" uniqKey="Millan J">JC Millán</name>
</author>
<author><name sortKey="Ortega, A" uniqKey="Ortega A">A Ortega</name>
</author>
<author><name sortKey="Iglesias, E" uniqKey="Iglesias E">E Iglesias</name>
</author>
<author><name sortKey="Pent N, E" uniqKey="Pent N E">E Pentón</name>
</author>
<author><name sortKey="Martin, Z" uniqKey="Martin Z">Z Martín</name>
</author>
<author><name sortKey="Perez, J" uniqKey="Perez J">J Pérez</name>
</author>
<author><name sortKey="Diaz, M" uniqKey="Diaz M">M Díaz</name>
</author>
<author><name sortKey="Duarte, Ca" uniqKey="Duarte C">CA Duarte</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ricciardi, A" uniqKey="Ricciardi A">A Ricciardi</name>
</author>
<author><name sortKey="Dalton, Jp" uniqKey="Dalton J">JP Dalton</name>
</author>
<author><name sortKey="Ndao, M" uniqKey="Ndao M">M Ndao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stack, Cm" uniqKey="Stack C">CM Stack</name>
</author>
<author><name sortKey="Dalton, Jp" uniqKey="Dalton J">JP Dalton</name>
</author>
<author><name sortKey="Cunneen, M" uniqKey="Cunneen M">M Cunneen</name>
</author>
<author><name sortKey="Donnelly, S" uniqKey="Donnelly S">S Donnelly</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Frey, A" uniqKey="Frey A">A Frey</name>
</author>
<author><name sortKey="Di Canzio, J" uniqKey="Di Canzio J">J Di Canzio</name>
</author>
<author><name sortKey="Zurakowski, D" uniqKey="Zurakowski D">D Zurakowski</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Plante, M" uniqKey="Plante M">M Plante</name>
</author>
<author><name sortKey="Jones, T" uniqKey="Jones T">T Jones</name>
</author>
<author><name sortKey="Allard, F" uniqKey="Allard F">F Allard</name>
</author>
<author><name sortKey="Torossian, K" uniqKey="Torossian K">K Torossian</name>
</author>
<author><name sortKey="Gauthier, J" uniqKey="Gauthier J">J Gauthier</name>
</author>
<author><name sortKey="St Felix, N" uniqKey="St Felix N">N St-Félix</name>
</author>
<author><name sortKey="White, Gl" uniqKey="White G">GL White</name>
</author>
<author><name sortKey="Lowell, Gh" uniqKey="Lowell G">GH Lowell</name>
</author>
<author><name sortKey="Burt, Ds" uniqKey="Burt D">DS Burt</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mcmanus, Dp" uniqKey="Mcmanus D">DP McManus</name>
</author>
<author><name sortKey="Loukas, A" uniqKey="Loukas A">A Loukas</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="El Ridi, R" uniqKey="El Ridi R">R El Ridi</name>
</author>
<author><name sortKey="Tallima, H" uniqKey="Tallima H">H Tallima</name>
</author>
<author><name sortKey="Selim, S" uniqKey="Selim S">S Selim</name>
</author>
<author><name sortKey="Donnelly, S" uniqKey="Donnelly S">S Donnelly</name>
</author>
<author><name sortKey="Cotton, S" uniqKey="Cotton S">S Cotton</name>
</author>
<author><name sortKey="Gonzales Santana, B" uniqKey="Gonzales Santana B">B Gonzales Santana</name>
</author>
<author><name sortKey="Dalton, Jp" uniqKey="Dalton J">JP Dalton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cheever, Aw" uniqKey="Cheever A">AW Cheever</name>
</author>
<author><name sortKey="Kamel, Ia" uniqKey="Kamel I">IA Kamel</name>
</author>
<author><name sortKey="Elwi, Am" uniqKey="Elwi A">AM Elwi</name>
</author>
<author><name sortKey="Mosimann, Je" uniqKey="Mosimann J">JE Mosimann</name>
</author>
<author><name sortKey="Danner, R" uniqKey="Danner R">R Danner</name>
</author>
<author><name sortKey="Sippel, Je" uniqKey="Sippel J">JE Sippel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Geboes, K" uniqKey="Geboes K">K Geboes</name>
</author>
<author><name sortKey="El Dosoky, I" uniqKey="El Dosoky I">I El-Dosoky</name>
</author>
<author><name sortKey="El Wahab, A" uniqKey="El Wahab A">A El-Wahab</name>
</author>
<author><name sortKey="Abou Almagd, K" uniqKey="Abou Almagd K">K Abou Almagd</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mohamed, Ar" uniqKey="Mohamed A">AR Mohamed</name>
</author>
<author><name sortKey="Al Karawi, M" uniqKey="Al Karawi M">M Al Karawi</name>
</author>
<author><name sortKey="Yasawy, Mi" uniqKey="Yasawy M">MI Yasawy</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ganley Leal, Lm" uniqKey="Ganley Leal L">LM Ganley-Leal</name>
</author>
<author><name sortKey="Guarner, J" uniqKey="Guarner J">J Guarner</name>
</author>
<author><name sortKey="Todd, Cw" uniqKey="Todd C">CW Todd</name>
</author>
<author><name sortKey="Da Ara, Aa" uniqKey="Da Ara A">AA Da’Dara</name>
</author>
<author><name sortKey="Freeman, Gl" uniqKey="Freeman G">GL Freeman</name>
</author>
<author><name sortKey="Boyer, Ae" uniqKey="Boyer A">AE Boyer</name>
</author>
<author><name sortKey="Harn, Da" uniqKey="Harn D">DA Harn</name>
</author>
<author><name sortKey="Secor, We" uniqKey="Secor W">WE Secor</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Minard, P" uniqKey="Minard P">P Minard</name>
</author>
<author><name sortKey="Dean, Da" uniqKey="Dean D">DA Dean</name>
</author>
<author><name sortKey="Jacobson, Rh" uniqKey="Jacobson R">RH Jacobson</name>
</author>
<author><name sortKey="Vannier, We" uniqKey="Vannier W">WE Vannier</name>
</author>
<author><name sortKey="Murrell, Kd" uniqKey="Murrell K">KD Murrell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sher, A" uniqKey="Sher A">A Sher</name>
</author>
<author><name sortKey="Hieny, S" uniqKey="Hieny S">S Hieny</name>
</author>
<author><name sortKey="James, Sl" uniqKey="James S">SL James</name>
</author>
<author><name sortKey="Asofsky, R" uniqKey="Asofsky R">R Asofsky</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wilson, Ra" uniqKey="Wilson R">RA Wilson</name>
</author>
<author><name sortKey="Coulson, Ps" uniqKey="Coulson P">PS Coulson</name>
</author>
<author><name sortKey="Mountford, Ap" uniqKey="Mountford A">AP Mountford</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Byram, Je" uniqKey="Byram J">JE Byram</name>
</author>
<author><name sortKey="Doenhoff, Mj" uniqKey="Doenhoff M">MJ Doenhoff</name>
</author>
<author><name sortKey="Musallam, R" uniqKey="Musallam R">R Musallam</name>
</author>
<author><name sortKey="Brink, Lh" uniqKey="Brink L">LH Brink</name>
</author>
<author><name sortKey="Von Lichtenberg, F" uniqKey="Von Lichtenberg F">F Von Lichtenberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Doenhoff, M" uniqKey="Doenhoff M">M Doenhoff</name>
</author>
<author><name sortKey="Musallam, R" uniqKey="Musallam R">R Musallam</name>
</author>
<author><name sortKey="Bain, J" uniqKey="Bain J">J Bain</name>
</author>
<author><name sortKey="Mcgregor, A" uniqKey="Mcgregor A">A McGregor</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mangold, Bl" uniqKey="Mangold B">BL Mangold</name>
</author>
<author><name sortKey="Dean, Da" uniqKey="Dean D">DA Dean</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Melo, Tt" uniqKey="Melo T">TT Melo</name>
</author>
<author><name sortKey="Sena, Ic" uniqKey="Sena I">IC Sena</name>
</author>
<author><name sortKey="Araujo, N" uniqKey="Araujo N">N Araujo</name>
</author>
<author><name sortKey="Fonseca, Ct" uniqKey="Fonseca C">CT Fonseca</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Torben, W" uniqKey="Torben W">W Torben</name>
</author>
<author><name sortKey="Ahmad, G" uniqKey="Ahmad G">G Ahmad</name>
</author>
<author><name sortKey="Zhang, W" uniqKey="Zhang W">W Zhang</name>
</author>
<author><name sortKey="Siddiqui, Aa" uniqKey="Siddiqui A">AA Siddiqui</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kariuki, Tm" uniqKey="Kariuki T">TM Kariuki</name>
</author>
<author><name sortKey="Farah, Io" uniqKey="Farah I">IO Farah</name>
</author>
<author><name sortKey="Yole, Ds" uniqKey="Yole D">DS Yole</name>
</author>
<author><name sortKey="Mwenda, Jm" uniqKey="Mwenda J">JM Mwenda</name>
</author>
<author><name sortKey="Van Dam, Gj" uniqKey="Van Dam G">GJ Van Dam</name>
</author>
<author><name sortKey="Deelder, Am" uniqKey="Deelder A">AM Deelder</name>
</author>
<author><name sortKey="Wilson, Ra" uniqKey="Wilson R">RA Wilson</name>
</author>
<author><name sortKey="Coulson, Ps" uniqKey="Coulson P">PS Coulson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wilson, Ra" uniqKey="Wilson R">RA Wilson</name>
</author>
<author><name sortKey="Langermans, Ja" uniqKey="Langermans J">JA Langermans</name>
</author>
<author><name sortKey="Van Dam, Gj" uniqKey="Van Dam G">GJ Van Dam</name>
</author>
<author><name sortKey="Vervenne, Ra" uniqKey="Vervenne R">RA Vervenne</name>
</author>
<author><name sortKey="Hall, Sl" uniqKey="Hall S">SL Hall</name>
</author>
<author><name sortKey="Borges, Wc" uniqKey="Borges W">WC Borges</name>
</author>
<author><name sortKey="Dillon, Gp" uniqKey="Dillon G">GP Dillon</name>
</author>
<author><name sortKey="Thomas, Aw" uniqKey="Thomas A">AW Thomas</name>
</author>
<author><name sortKey="Coulson, Ps" uniqKey="Coulson P">PS Coulson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wilson, Ra" uniqKey="Wilson R">RA Wilson</name>
</author>
<author><name sortKey="Coulson, Ps" uniqKey="Coulson P">PS Coulson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Torben, W" uniqKey="Torben W">W Torben</name>
</author>
<author><name sortKey="Ahmad, G" uniqKey="Ahmad G">G Ahmad</name>
</author>
<author><name sortKey="Zhang, W" uniqKey="Zhang W">W Zhang</name>
</author>
<author><name sortKey="Nash, S" uniqKey="Nash S">S Nash</name>
</author>
<author><name sortKey="Le, L" uniqKey="Le L">L Le</name>
</author>
<author><name sortKey="Karmakar, S" uniqKey="Karmakar S">S Karmakar</name>
</author>
<author><name sortKey="Siddiqui, Aa" uniqKey="Siddiqui A">AA Siddiqui</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Martin, Rm" uniqKey="Martin R">RM Martin</name>
</author>
<author><name sortKey="Brady, Jl" uniqKey="Brady J">JL Brady</name>
</author>
<author><name sortKey="Lee, Am" uniqKey="Lee A">AM Lee</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Viana, Ir" uniqKey="Viana I">IR Viana</name>
</author>
<author><name sortKey="Sher, A" uniqKey="Sher A">A Sher</name>
</author>
<author><name sortKey="Carvalho, Os" uniqKey="Carvalho O">OS Carvalho</name>
</author>
<author><name sortKey="Massara, Cl" uniqKey="Massara C">CL Massara</name>
</author>
<author><name sortKey="Eloi Santos, Sm" uniqKey="Eloi Santos S">SM Eloi-Santos</name>
</author>
<author><name sortKey="Pearce, Ej" uniqKey="Pearce E">EJ Pearce</name>
</author>
<author><name sortKey="Colley, Dg" uniqKey="Colley D">DG Colley</name>
</author>
<author><name sortKey="Gazzinelli, G" uniqKey="Gazzinelli G">G Gazzinelli</name>
</author>
<author><name sortKey="Correa Oliveira, R" uniqKey="Correa Oliveira R">R Correa-Oliveira</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="Street, M" uniqKey="Street M">M Street</name>
</author>
<author><name sortKey="Coulson, Ps" uniqKey="Coulson P">PS Coulson</name>
</author>
<author><name sortKey="Sadler, C" uniqKey="Sadler C">C Sadler</name>
</author>
<author><name sortKey="Warnock, Lj" uniqKey="Warnock L">LJ Warnock</name>
</author>
<author><name sortKey="Mclaughlin, D" uniqKey="Mclaughlin D">D McLaughlin</name>
</author>
<author><name sortKey="Bluethmann, H" uniqKey="Bluethmann H">H Bluethmann</name>
</author>
<author><name sortKey="Wilson, Ra" uniqKey="Wilson R">RA Wilson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Varaldo, Pb" uniqKey="Varaldo P">PB Varaldo</name>
</author>
<author><name sortKey="Leite, Lc" uniqKey="Leite L">LC Leite</name>
</author>
<author><name sortKey="Dias, Wo" uniqKey="Dias W">WO Dias</name>
</author>
<author><name sortKey="Miyaji, En" uniqKey="Miyaji E">EN Miyaji</name>
</author>
<author><name sortKey="Torres, Fi" uniqKey="Torres F">FI Torres</name>
</author>
<author><name sortKey="Gebara, Vc" uniqKey="Gebara V">VC Gebara</name>
</author>
<author><name sortKey="Armoa, Gr" uniqKey="Armoa G">GR Armôa</name>
</author>
<author><name sortKey="Campos, As" uniqKey="Campos A">AS Campos</name>
</author>
<author><name sortKey="Matos, Dc" uniqKey="Matos D">DC Matos</name>
</author>
<author><name sortKey="Winter, N" uniqKey="Winter N">N Winter</name>
</author>
<author><name sortKey="Gicquel, B" uniqKey="Gicquel B">B Gicquel</name>
</author>
<author><name sortKey="Vilar, Mm" uniqKey="Vilar M">MM Vilar</name>
</author>
<author><name sortKey="Mcfadden, J" uniqKey="Mcfadden J">J McFadden</name>
</author>
<author><name sortKey="Almeida, Ms" uniqKey="Almeida M">MS Almeida</name>
</author>
<author><name sortKey="Tendler, M" uniqKey="Tendler M">M Tendler</name>
</author>
<author><name sortKey="Mcintosh, D" uniqKey="Mcintosh D">D McIntosh</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ahmad, G" uniqKey="Ahmad G">G Ahmad</name>
</author>
<author><name sortKey="Zhang, W" uniqKey="Zhang W">W Zhang</name>
</author>
<author><name sortKey="Torben, W" uniqKey="Torben W">W Torben</name>
</author>
<author><name sortKey="Haskins, C" uniqKey="Haskins C">C Haskins</name>
</author>
<author><name sortKey="Diggs, S" uniqKey="Diggs S">S Diggs</name>
</author>
<author><name sortKey="Noor, Z" uniqKey="Noor Z">Z Noor</name>
</author>
<author><name sortKey="Le, L" uniqKey="Le L">L Le</name>
</author>
<author><name sortKey="Siddiqui, Aa" uniqKey="Siddiqui A">AA Siddiqui</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pearson, Ms" uniqKey="Pearson M">MS Pearson</name>
</author>
<author><name sortKey="Pickering, Da" uniqKey="Pickering D">DA Pickering</name>
</author>
<author><name sortKey="Mcsorley, Hj" uniqKey="Mcsorley H">HJ McSorley</name>
</author>
<author><name sortKey="Bethony, Jm" uniqKey="Bethony J">JM Bethony</name>
</author>
<author><name sortKey="Tribolet, L" uniqKey="Tribolet L">L Tribolet</name>
</author>
<author><name sortKey="Dougall, Am" uniqKey="Dougall A">AM Dougall</name>
</author>
<author><name sortKey="Hotez, Pj" uniqKey="Hotez P">PJ Hotez</name>
</author>
<author><name sortKey="Loukas, A" uniqKey="Loukas A">A Loukas</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="El Ridi, R" uniqKey="El Ridi R">R El Ridi</name>
</author>
<author><name sortKey="Tallima, H" uniqKey="Tallima H">H Tallima</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tallima, H" uniqKey="Tallima H">H Tallima</name>
</author>
<author><name sortKey="Salah, M" uniqKey="Salah M">M Salah</name>
</author>
<author><name sortKey="Guirguis, Fr" uniqKey="Guirguis F">FR Guirguis</name>
</author>
<author><name sortKey="El Ridi, R" uniqKey="El Ridi R">R El Ridi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Comin, F" uniqKey="Comin F">F Comin</name>
</author>
<author><name sortKey="Speziali, E" uniqKey="Speziali E">E Speziali</name>
</author>
<author><name sortKey="Correa Oliveira, R" uniqKey="Correa Oliveira R">R Correa-Oliveira</name>
</author>
<author><name sortKey="Faria, Am" uniqKey="Faria A">AM Faria</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Infect Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">BMC Infect. Dis</journal-id>
<journal-title-group><journal-title>BMC Infectious Diseases</journal-title>
</journal-title-group>
<issn pub-type="epub">1471-2334</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26945988</article-id>
<article-id pub-id-type="pmc">4779570</article-id>
<article-id pub-id-type="publisher-id">1444</article-id>
<article-id pub-id-type="doi">10.1186/s12879-016-1444-z</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>A vaccine consisting of <italic>Schistosoma mansoni</italic>
cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Ricciardi</surname>
<given-names>Alessandra</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
<xref ref-type="aff" rid="Aff4"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Visitsunthorn</surname>
<given-names>Kittipos</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dalton</surname>
<given-names>John P.</given-names>
</name>
<xref ref-type="aff" rid="Aff2"></xref>
<xref ref-type="aff" rid="Aff3"></xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Ndao</surname>
<given-names>Momar</given-names>
</name>
<address><email>momar.ndao@mcgill.ca</email>
</address>
<xref ref-type="aff" rid="Aff1"></xref>
<xref ref-type="aff" rid="Aff4"></xref>
</contrib>
<aff id="Aff1"><label></label>
Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</aff>
<aff id="Aff2"><label></label>
Institute of Parasitology, McGill University, Montreal, QC Canada</aff>
<aff id="Aff3"><label></label>
School of Biological Sciences, Medical Biology Centre (MBC) Queen’s University Belfast, Belfast, Northern Ireland</aff>
<aff id="Aff4"><label></label>
National Reference Center for Parasitology, Research Institute of the McGill University Health Center, Montreal, QC Canada</aff>
</contrib-group>
<pub-date pub-type="epub"><day>5</day>
<month>3</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>5</day>
<month>3</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection"><year>2016</year>
</pub-date>
<volume>16</volume>
<elocation-id>112</elocation-id>
<history><date date-type="received"><day>22</day>
<month>11</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>24</day>
<month>2</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>© Ricciardi et al. 2016</copyright-statement>
<license license-type="OpenAccess"><license-p><bold>Open Access</bold>
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated.</license-p>
</license>
</permissions>
<abstract id="Abs1"><sec><title>Background</title>
<p>Schistosomiasis is the most important human helminth infection due to its impact on public health. The clinical manifestations are chronic and significantly decrease an individual’s quality of life. Infected individuals suffer from long-term organ pathologies including fibrosis which eventually leads to organ failure. The development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission.</p>
</sec>
<sec><title>Method</title>
<p>Our group has chosen <italic>Schistosoma mansoni</italic>
(Sm) cathepsin B, a peptidase involved in parasite feeding, as a prospective vaccine candidate. Our experimental formulation consisted of recombinant Sm-cathepsin B formulated in Montanide ISA 720 VG, a squalene based adjuvant containing a mannide mono-oleate emulsifier. Parasitological burden was assessed by determining adult worm, hepatic egg, and intestinal egg numbers in each mouse. Serum was used in ELISAs to evaluate production of antigen-specific antibodies, and isolated splenocytes were stimulated with the antigen for the analysis of cytokine secretion levels.</p>
</sec>
<sec><title>Results</title>
<p>The Sm-cathepsin B and Montanide formulation conferred protection against a challenge infection by significantly reducing all forms of parasitological burdens. Worm burden, hepatic egg burden and intestinal egg burden were decreased by 60 %, 62 %, and 56 %, respectively in immunized animals compared to controls (<italic>P</italic>
= 0.0002, <italic>P</italic>
< 0.0001, <italic>P</italic>
= 0.0009, respectively). Immunizations with the vaccine elicited robust production of Sm-cathepsin B specific antibodies (endpoint titers = 122,880). Both antigen-specific IgG1 and IgG2c titers were observed, with the former having more elevated titers. Furthermore, splenocytes isolated from the immunized animals, compared to control animals, secreted higher levels of key Th1 cytokines, IFN-γ, IL-12, and TNF-α, as well as the Th2 cytokines IL-5 and IL-4 when stimulated with recombinant Sm-cathepsin B. The Th17 cytokine IL-17, the chemokine CCL5, and the growth factor GM-CSF were also significantly increased in the immunized animals compared to the controls.</p>
</sec>
<sec><title>Conclusion</title>
<p>The formulation tested in this study was able to significantly reduce all forms of parasite burden, stimulate robust production of antigen-specific antibodies, and induce a mixed Th1/Th2 response. These results highlight the potential of Sm-cathepsin B/Montanide ISA 720 VG as a vaccine candidate against schistosomiasis.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s12879-016-1444-z) contains supplementary material, which is available to authorized users.</p>
</sec>
</abstract>
<kwd-group xml:lang="en"><title>Keywords</title>
<kwd>Schistosomiasis</kwd>
<kwd>Vaccine</kwd>
<kwd>Cathepsin B</kwd>
<kwd>Montanide ISA 720 VG</kwd>
<kwd>Antigen-specific antibodies</kwd>
<kwd>Cytokine production</kwd>
</kwd-group>
<funding-group><award-group><funding-source><institution>Public Health Agency of Canada</institution>
</funding-source>
<award-id>MOA 4500299739</award-id>
<principal-award-recipient><name><surname>Ndao</surname>
<given-names>Momar</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2016</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Terre/explor/CobaltMaghrebV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000094 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000094 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Terre |area= CobaltMaghrebV1 |flux= Pmc |étape= Curation |type= RBID |clé= PMC:4779570 |texte= A vaccine consisting of Schistosoma mansoni cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:26945988" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \ | NlmPubMed2Wicri -a CobaltMaghrebV1
This area was generated with Dilib version V0.6.32. |