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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Immunization with cross-conserved H1N1 influenza CD4<sup>+</sup> T-cell epitopes lowers viral burden in HLA DR3 transgenic mice</title><author><name sortKey="Moise, Leonard" sort="Moise, Leonard" uniqKey="Moise L" first="Leonard" last="Moise">Leonard Moise</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Institute for Immunology and Informatics; University of Rhode Island; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Tassone, Ryan" sort="Tassone, Ryan" uniqKey="Tassone R" first="Ryan" last="Tassone">Ryan Tassone</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Latimer, Howard" sort="Latimer, Howard" uniqKey="Latimer H" first="Howard" last="Latimer">Howard Latimer</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Terry, Frances" sort="Terry, Frances" uniqKey="Terry F" first="Frances" last="Terry">Frances Terry</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Levitz, Lauren" sort="Levitz, Lauren" uniqKey="Levitz L" first="Lauren" last="Levitz">Lauren Levitz</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Haran, John P" sort="Haran, John P" uniqKey="Haran J" first="John P" last="Haran">John P. Haran</name><affiliation><nlm:aff id="A3">Brown University Warren Alpert Medical School; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Ross, Ted M" sort="Ross, Ted M" uniqKey="Ross T" first="Ted M" last="Ross">Ted M. Ross</name><affiliation><nlm:aff id="A4">Vaccine & Gene Therapy Institute of Florida; Port Saint Lucie, FL USA</nlm:aff></affiliation></author><author><name sortKey="Boyle, Christine" sort="Boyle, Christine" uniqKey="Boyle C" first="Christine" last="Boyle">Christine Boyle</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Martin, William D" sort="Martin, William D" uniqKey="Martin W" first="William D" last="Martin">William D. Martin</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="De Groot, Anne S" sort="De Groot, Anne S" uniqKey="De Groot A" first="Anne S" last="De Groot">Anne S. De Groot</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Institute for Immunology and Informatics; University of Rhode Island; Providence, RI USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24045788</idno><idno type="pmc">3906390</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906390</idno><idno type="RBID">PMC:3906390</idno><idno type="doi">10.4161/hv.26511</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000697</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000697</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Immunization with cross-conserved H1N1 influenza CD4<sup>+</sup> T-cell epitopes lowers viral burden in HLA DR3 transgenic mice</title><author><name sortKey="Moise, Leonard" sort="Moise, Leonard" uniqKey="Moise L" first="Leonard" last="Moise">Leonard Moise</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Institute for Immunology and Informatics; University of Rhode Island; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Tassone, Ryan" sort="Tassone, Ryan" uniqKey="Tassone R" first="Ryan" last="Tassone">Ryan Tassone</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Latimer, Howard" sort="Latimer, Howard" uniqKey="Latimer H" first="Howard" last="Latimer">Howard Latimer</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Terry, Frances" sort="Terry, Frances" uniqKey="Terry F" first="Frances" last="Terry">Frances Terry</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Levitz, Lauren" sort="Levitz, Lauren" uniqKey="Levitz L" first="Lauren" last="Levitz">Lauren Levitz</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Haran, John P" sort="Haran, John P" uniqKey="Haran J" first="John P" last="Haran">John P. Haran</name><affiliation><nlm:aff id="A3">Brown University Warren Alpert Medical School; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Ross, Ted M" sort="Ross, Ted M" uniqKey="Ross T" first="Ted M" last="Ross">Ted M. Ross</name><affiliation><nlm:aff id="A4">Vaccine & Gene Therapy Institute of Florida; Port Saint Lucie, FL USA</nlm:aff></affiliation></author><author><name sortKey="Boyle, Christine" sort="Boyle, Christine" uniqKey="Boyle C" first="Christine" last="Boyle">Christine Boyle</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="Martin, William D" sort="Martin, William D" uniqKey="Martin W" first="William D" last="Martin">William D. Martin</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation></author><author><name sortKey="De Groot, Anne S" sort="De Groot, Anne S" uniqKey="De Groot A" first="Anne S" last="De Groot">Anne S. De Groot</name><affiliation><nlm:aff id="A1">EpiVax, Inc.; Providence, RI USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Institute for Immunology and Informatics; University of Rhode Island; Providence, RI 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>The emergence of the pandemic H1N1 strain of influenza in 2009 was associated with a unique w-shaped age-related susceptibility curve, with higher incidence of morbidity and mortality among young persons and lower incidence among older persons, also observed during the 1918 influenza pandemic. Pre-existing H1N1 antibodies were not cross-reactive with the prior seasonal vaccine, forcing influenza experts to scramble to develop a new vaccine specific for the pandemic virus. We hypothesized that response to T-cell epitopes that are cross-conserved between pandemic H1N1 and the 2008 seasonal influenza vaccine strains might have contributed to partial protection from clinical illness among older adults, despite the lack of cross-reactive humoral immunity. Using immunoinformatics tools, we previously identified hemagglutinin and neuraminidase epitopes that were highly conserved between seasonal and pandemic H1N1. Here, we validated predicted CD4<sup>+</sup> T-cell epitopes for their ability to bind HLA and to stimulate interferon-γ production in peripheral blood mononuclear cells from a cohort of donors presenting with influenza-like illness during the 2009 pandemic and a separate cohort immunized with trivalent influenza vaccine in 2011. A limited-epitope heterologous DNA-prime/peptide-boost vaccine composed of these sequences stimulated immune responses and lowered lung viral loads in HLA DR3 transgenic mice challenged with pandemic 2009 H1N1 influenza. Cross-priming with conserved influenza T-cell epitopes such as these may be critically important to T cell-mediated protection against pandemic H1N1 in the absence of cross-protective antibodies.</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">24045788</article-id><article-id pub-id-type="pmc">3906390</article-id><article-id pub-id-type="publisher-id">2012HV0432</article-id><article-id pub-id-type="doi">10.4161/hv.26511</article-id><article-id pub-id-type="pii">26511</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></article-categories><title-group><article-title>Immunization with cross-conserved H1N1 influenza CD4<sup>+</sup> T-cell epitopes lowers viral burden in HLA DR3 transgenic mice</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Moise</surname><given-names>Leonard</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref><xref ref-type="aff" rid="A2"><sup>2</sup></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>Tassone</surname><given-names>Ryan</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Latimer</surname><given-names>Howard</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Terry</surname><given-names>Frances</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Levitz</surname><given-names>Lauren</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Haran</surname><given-names>John P</given-names></name><xref ref-type="aff" rid="A3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ross</surname><given-names>Ted M</given-names></name><xref ref-type="aff" rid="A4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Boyle</surname><given-names>Christine</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Martin</surname><given-names>William D</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>De Groot</surname><given-names>Anne S</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref><xref ref-type="aff" rid="A2"><sup>2</sup></xref></contrib><aff id="A1"><label>1</label>EpiVax, Inc.; Providence, RI USA</aff><aff id="A2"><label>2</label>Institute for Immunology and Informatics; University of Rhode Island; Providence, RI USA</aff><aff id="A3"><label>3</label>Brown University Warren Alpert Medical School; Providence, RI USA</aff><aff id="A4"><label>4</label>Vaccine & Gene Therapy Institute of Florida; Port Saint Lucie, FL USA</aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>Correspondence to: Leonard Moise, Email: <email xlink:href="lmoise@epivax.com">lmoise@epivax.com</email></corresp></author-notes><pub-date pub-type="ppub"><day>01</day><month>10</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>17</day><month>9</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>17</day><month>9</month><year>2013</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>9</volume><issue>10</issue><fpage>2060</fpage><lpage>2068</lpage><history><date date-type="received"><day>10</day><month>6</month><year>2013</year></date><date date-type="accepted"><day>17</day><month>9</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2013 Landes Bioscience</copyright-statement><copyright-year>2013</copyright-year></permissions><abstract><p>The emergence of the pandemic H1N1 strain of influenza in 2009 was associated with a unique w-shaped age-related susceptibility curve, with higher incidence of morbidity and mortality among young persons and lower incidence among older persons, also observed during the 1918 influenza pandemic. Pre-existing H1N1 antibodies were not cross-reactive with the prior seasonal vaccine, forcing influenza experts to scramble to develop a new vaccine specific for the pandemic virus. We hypothesized that response to T-cell epitopes that are cross-conserved between pandemic H1N1 and the 2008 seasonal influenza vaccine strains might have contributed to partial protection from clinical illness among older adults, despite the lack of cross-reactive humoral immunity. Using immunoinformatics tools, we previously identified hemagglutinin and neuraminidase epitopes that were highly conserved between seasonal and pandemic H1N1. Here, we validated predicted CD4<sup>+</sup> T-cell epitopes for their ability to bind HLA and to stimulate interferon-γ production in peripheral blood mononuclear cells from a cohort of donors presenting with influenza-like illness during the 2009 pandemic and a separate cohort immunized with trivalent influenza vaccine in 2011. A limited-epitope heterologous DNA-prime/peptide-boost vaccine composed of these sequences stimulated immune responses and lowered lung viral loads in HLA DR3 transgenic mice challenged with pandemic 2009 H1N1 influenza. Cross-priming with conserved influenza T-cell epitopes such as these may be critically important to T cell-mediated protection against pandemic H1N1 in the absence of cross-protective antibodies.</p></abstract><kwd-group kwd-group-type="author"><title>Keywords: </title><kwd>T-cell epitope</kwd><kwd>immunoinformatics</kwd><kwd>influenza</kwd><kwd>vaccine</kwd><kwd>pandemic</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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