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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
. </pmc-comment>
<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>
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