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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge</title><author><name sortKey="Mallajosyula, Jyothi K" sort="Mallajosyula, Jyothi K" uniqKey="Mallajosyula J" first="Jyothi K" last="Mallajosyula">Jyothi K. Mallajosyula</name><affiliation><nlm:aff id="A1">Touro University California; Vallejo, CA USA</nlm:aff></affiliation></author><author><name sortKey="Hiatt, Ernie" sort="Hiatt, Ernie" uniqKey="Hiatt E" first="Ernie" last="Hiatt">Ernie Hiatt</name><affiliation><nlm:aff id="A2">Kentucky BioProcessing LLC; Owensboro, KY USA</nlm:aff></affiliation></author><author><name sortKey="Hume, Steve" sort="Hume, Steve" uniqKey="Hume S" first="Steve" last="Hume">Steve Hume</name><affiliation><nlm:aff id="A2">Kentucky BioProcessing LLC; Owensboro, KY USA</nlm:aff></affiliation></author><author><name sortKey="Johnson, Ashley" sort="Johnson, Ashley" uniqKey="Johnson A" first="Ashley" last="Johnson">Ashley Johnson</name><affiliation><nlm:aff id="A2">Kentucky BioProcessing LLC; Owensboro, KY USA</nlm:aff></affiliation></author><author><name sortKey="Jeevan, Trushar" sort="Jeevan, Trushar" uniqKey="Jeevan T" first="Trushar" last="Jeevan">Trushar Jeevan</name><affiliation><nlm:aff id="A3">St. Jude Children's Research Hospital; Memphis, TN USA</nlm:aff></affiliation></author><author><name sortKey="Chikwamba, Rachel" sort="Chikwamba, Rachel" uniqKey="Chikwamba R" first="Rachel" last="Chikwamba">Rachel Chikwamba</name><affiliation><nlm:aff id="A4">Council for Scientific and Industrial Research; Pretoria, South Africa</nlm:aff></affiliation></author><author><name sortKey="Pogue, Gregory P" sort="Pogue, Gregory P" uniqKey="Pogue G" first="Gregory P" last="Pogue">Gregory P. Pogue</name><affiliation><nlm:aff id="A2">Kentucky BioProcessing LLC; Owensboro, KY USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">IC2 Institute; The University of Texas at Austin; Austin, TX USA</nlm:aff></affiliation></author><author><name sortKey="Bratcher, Barry" sort="Bratcher, Barry" uniqKey="Bratcher B" first="Barry" last="Bratcher">Barry Bratcher</name><affiliation><nlm:aff id="A2">Kentucky BioProcessing LLC; Owensboro, KY USA</nlm:aff></affiliation></author><author><name sortKey="Haydon, Hugh" sort="Haydon, Hugh" uniqKey="Haydon H" first="Hugh" last="Haydon">Hugh Haydon</name><affiliation><nlm:aff id="A2">Kentucky BioProcessing LLC; Owensboro, KY USA</nlm:aff></affiliation></author><author><name sortKey="Webby, Richard J" sort="Webby, Richard J" uniqKey="Webby R" first="Richard J" last="Webby">Richard J. Webby</name><affiliation><nlm:aff id="A3">St. Jude Children's Research Hospital; Memphis, TN USA</nlm:aff></affiliation></author><author><name sortKey="Mccormick, Alison A" sort="Mccormick, Alison A" uniqKey="Mccormick A" first="Alison A" last="Mccormick">Alison A. Mccormick</name><affiliation><nlm:aff id="A1">Touro University California; Vallejo, CA USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24378714</idno><idno type="pmc">4130260</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130260</idno><idno type="RBID">PMC:4130260</idno><idno type="doi">10.4161/hv.27567</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000698</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000698</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge</title><author><name sortKey="Mallajosyula, Jyothi K" sort="Mallajosyula, Jyothi K" uniqKey="Mallajosyula J" first="Jyothi K" last="Mallajosyula">Jyothi K. Mallajosyula</name><affiliation><nlm:aff id="A1">Touro University California; Vallejo, CA USA</nlm:aff></affiliation></author><author><name sortKey="Hiatt, Ernie" sort="Hiatt, Ernie" uniqKey="Hiatt E" first="Ernie" last="Hiatt">Ernie Hiatt</name><affiliation><nlm:aff id="A2">Kentucky BioProcessing LLC; Owensboro, KY USA</nlm:aff></affiliation></author><author><name sortKey="Hume, Steve" sort="Hume, Steve" uniqKey="Hume S" first="Steve" last="Hume">Steve Hume</name><affiliation><nlm:aff id="A2">Kentucky BioProcessing LLC; Owensboro, KY USA</nlm:aff></affiliation></author><author><name sortKey="Johnson, Ashley" sort="Johnson, Ashley" uniqKey="Johnson A" first="Ashley" last="Johnson">Ashley Johnson</name><affiliation><nlm:aff id="A2">Kentucky BioProcessing LLC; Owensboro, KY USA</nlm:aff></affiliation></author><author><name sortKey="Jeevan, Trushar" sort="Jeevan, Trushar" uniqKey="Jeevan T" first="Trushar" last="Jeevan">Trushar Jeevan</name><affiliation><nlm:aff id="A3">St. Jude Children's Research Hospital; Memphis, TN USA</nlm:aff></affiliation></author><author><name sortKey="Chikwamba, Rachel" sort="Chikwamba, Rachel" uniqKey="Chikwamba R" first="Rachel" last="Chikwamba">Rachel Chikwamba</name><affiliation><nlm:aff id="A4">Council for Scientific and Industrial Research; Pretoria, South Africa</nlm:aff></affiliation></author><author><name sortKey="Pogue, Gregory P" sort="Pogue, Gregory P" uniqKey="Pogue G" first="Gregory P" last="Pogue">Gregory P. Pogue</name><affiliation><nlm:aff id="A2">Kentucky BioProcessing LLC; Owensboro, KY USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">IC2 Institute; The University of Texas at Austin; Austin, TX USA</nlm:aff></affiliation></author><author><name sortKey="Bratcher, Barry" sort="Bratcher, Barry" uniqKey="Bratcher B" first="Barry" last="Bratcher">Barry Bratcher</name><affiliation><nlm:aff id="A2">Kentucky BioProcessing LLC; Owensboro, KY USA</nlm:aff></affiliation></author><author><name sortKey="Haydon, Hugh" sort="Haydon, Hugh" uniqKey="Haydon H" first="Hugh" last="Haydon">Hugh Haydon</name><affiliation><nlm:aff id="A2">Kentucky BioProcessing LLC; Owensboro, KY USA</nlm:aff></affiliation></author><author><name sortKey="Webby, Richard J" sort="Webby, Richard J" uniqKey="Webby R" first="Richard J" last="Webby">Richard J. Webby</name><affiliation><nlm:aff id="A3">St. Jude Children's Research Hospital; Memphis, TN USA</nlm:aff></affiliation></author><author><name sortKey="Mccormick, Alison A" sort="Mccormick, Alison A" uniqKey="Mccormick A" first="Alison A" last="Mccormick">Alison A. Mccormick</name><affiliation><nlm:aff id="A1">Touro University California; Vallejo, CA USA</nlm:aff></affiliation></author></analytic><series><title level="j">Human Vaccines & Immunotherapeutics</title><idno type="ISSN">2164-5515</idno><idno type="eISSN">2164-554X</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant hemagglutinin (HA) subunit protein are often of low potency, requiring high dose or boosting to generate a sustained immune response. We have improved the immunogenicity of a plant-made HA vaccine by chemical conjugation to the surface of the <italic>Tobacco mosaic virus</italic> (TMV) which is non infectious in mammals. We have previously shown that TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier. In this work, we tested several TMV-HA conjugation chemistries, and compared immunogenicity in mice as measured by anti-HA IgG titers and hemagglutination inhibition (HAI). Importantly, pre-existing immunity to TMV did not reduce initial or boosted titers. Further optimization included dosing with and without alum or oil-in water adjuvants. Surprisingly, we were able to stimulate potent immunogenicity and HAI titers with a single 15µg dose of HA as a TMV conjugate. We then evaluated the efficacy of the TMV-HA vaccine in a lethal virus challenge in mice. Our results show that a single dose of the TMV-HA conjugate vaccine is sufficient to generate 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H1N1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large quantities of highly effective flu vaccine from an otherwise low potency HA subunit protein.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Hum Vaccin Immunother</journal-id><journal-id journal-id-type="iso-abbrev">Hum Vaccin Immunother</journal-id><journal-id journal-id-type="publisher-id">HV</journal-id><journal-title-group><journal-title>Human Vaccines & Immunotherapeutics</journal-title></journal-title-group><issn pub-type="ppub">2164-5515</issn><issn pub-type="epub">2164-554X</issn><publisher><publisher-name>Landes Bioscience</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24378714</article-id><article-id pub-id-type="pmc">4130260</article-id><article-id pub-id-type="publisher-id">2013HV0418R1</article-id><article-id pub-id-type="doi">10.4161/hv.27567</article-id><article-id pub-id-type="pii">27567</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></article-categories><title-group><article-title>Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Mallajosyula</surname><given-names>Jyothi K</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hiatt</surname><given-names>Ernie</given-names></name><xref ref-type="aff" rid="A2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hume</surname><given-names>Steve</given-names></name><xref ref-type="aff" rid="A2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Johnson</surname><given-names>Ashley</given-names></name><xref ref-type="aff" rid="A2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jeevan</surname><given-names>Trushar</given-names></name><xref ref-type="aff" rid="A3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chikwamba</surname><given-names>Rachel</given-names></name><xref ref-type="aff" rid="A4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pogue</surname><given-names>Gregory P</given-names></name><xref ref-type="aff" rid="A2"><sup>2</sup></xref><xref ref-type="aff" rid="A5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bratcher</surname><given-names>Barry</given-names></name><xref ref-type="aff" rid="A2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Haydon</surname><given-names>Hugh</given-names></name><xref ref-type="aff" rid="A2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Webby</surname><given-names>Richard J</given-names></name><xref ref-type="aff" rid="A3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>McCormick</surname><given-names>Alison A</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><aff id="A1"><label>1</label>Touro University California; Vallejo, CA USA</aff><aff id="A2"><label>2</label>Kentucky BioProcessing LLC; Owensboro, KY USA</aff><aff id="A3"><label>3</label>St. Jude Children's Research Hospital; Memphis, TN USA</aff><aff id="A4"><label>4</label>Council for Scientific and Industrial Research; Pretoria, South Africa</aff><aff id="A5"><label>5</label>IC2 Institute; The University of Texas at Austin; Austin, TX USA</aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>Correspondence to: Alison A McCormick, Email: <email xlink:href="alison.mccormick@tu.edu">alison.mccormick@tu.edu</email></corresp></author-notes><pub-date pub-type="ppub"><day>01</day><month>3</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>30</day><month>12</month><year>2013</year></pub-date><volume>10</volume><issue>3</issue><fpage>586</fpage><lpage>595</lpage><history><date date-type="received"><day>04</day><month>10</month><year>2013</year></date><date date-type="rev-recd"><day>14</day><month>12</month><year>2013</year></date><date date-type="accepted"><day>18</day><month>12</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2014 Landes Bioscience</copyright-statement><copyright-year>2014</copyright-year></permissions><abstract><p>Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant hemagglutinin (HA) subunit protein are often of low potency, requiring high dose or boosting to generate a sustained immune response. We have improved the immunogenicity of a plant-made HA vaccine by chemical conjugation to the surface of the <italic>Tobacco mosaic virus</italic> (TMV) which is non infectious in mammals. We have previously shown that TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier. In this work, we tested several TMV-HA conjugation chemistries, and compared immunogenicity in mice as measured by anti-HA IgG titers and hemagglutination inhibition (HAI). Importantly, pre-existing immunity to TMV did not reduce initial or boosted titers. Further optimization included dosing with and without alum or oil-in water adjuvants. Surprisingly, we were able to stimulate potent immunogenicity and HAI titers with a single 15µg dose of HA as a TMV conjugate. We then evaluated the efficacy of the TMV-HA vaccine in a lethal virus challenge in mice. Our results show that a single dose of the TMV-HA conjugate vaccine is sufficient to generate 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H1N1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large quantities of highly effective flu vaccine from an otherwise low potency HA subunit protein.</p></abstract><kwd-group kwd-group-type="author"><title>Keywords: </title><kwd>Influenza</kwd><kwd>H1N1</kwd><kwd>plant made pharmaceuticals</kwd><kwd>HA subunit protein</kwd><kwd>vaccination</kwd><kwd>nanoparticle</kwd><kwd>dose sparing</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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