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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">NS-based Live Attenuated H1N1 Pandemic Vaccines Protect Mice and Ferrets</title>
<author><name sortKey="Zhou, Bin" sort="Zhou, Bin" uniqKey="Zhou B" first="Bin" last="Zhou">Bin Zhou</name>
<affiliation><nlm:aff id="A1">Wadsworth Center, New York State Department of Health, State University of New York, Albany, New York 12201</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York 12201</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name>
<affiliation><nlm:aff id="A1">Wadsworth Center, New York State Department of Health, State University of New York, Albany, New York 12201</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences (CAS), Wuhan, PR China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Belser, Jessica A" sort="Belser, Jessica A" uniqKey="Belser J" first="Jessica A." last="Belser">Jessica A. Belser</name>
<affiliation><nlm:aff id="A4">Immunology and Pathogenesis Branch, Influenza Division, NCIRD</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pearce, Melissa B" sort="Pearce, Melissa B" uniqKey="Pearce M" first="Melissa B." last="Pearce">Melissa B. Pearce</name>
<affiliation><nlm:aff id="A4">Immunology and Pathogenesis Branch, Influenza Division, NCIRD</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schmolke, Mirco" sort="Schmolke, Mirco" uniqKey="Schmolke M" first="Mirco" last="Schmolke">Mirco Schmolke</name>
<affiliation><nlm:aff id="A5">Department of Microbiology, Mount Sinai School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Subba, Anju X" sort="Subba, Anju X" uniqKey="Subba A" first="Anju X." last="Subba">Anju X. Subba</name>
<affiliation><nlm:aff id="A1">Wadsworth Center, New York State Department of Health, State University of New York, Albany, New York 12201</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Shi, Zhengli" sort="Shi, Zhengli" uniqKey="Shi Z" first="Zhengli" last="Shi">Zhengli Shi</name>
<affiliation><nlm:aff id="A3">State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences (CAS), Wuhan, PR China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zaki, Sherif R" sort="Zaki, Sherif R" uniqKey="Zaki S" first="Sherif R." last="Zaki">Sherif R. Zaki</name>
<affiliation><nlm:aff id="A6">Infectious Disease Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Blau, Dianna M" sort="Blau, Dianna M" uniqKey="Blau D" first="Dianna M." last="Blau">Dianna M. Blau</name>
<affiliation><nlm:aff id="A6">Infectious Disease Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name>
<affiliation><nlm:aff id="A5">Department of Microbiology, Mount Sinai School of Medicine, New York, New York</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A7">Institute of Global Health and Emerging Pathogens, Mount Sinai School of Medicine, New York, New York</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tumpey, Terrence M" sort="Tumpey, Terrence M" uniqKey="Tumpey T" first="Terrence M." last="Tumpey">Terrence M. Tumpey</name>
<affiliation><nlm:aff id="A4">Immunology and Pathogenesis Branch, Influenza Division, NCIRD</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wentworth, David E" sort="Wentworth, David E" uniqKey="Wentworth D" first="David E." last="Wentworth">David E. Wentworth</name>
<affiliation><nlm:aff id="A1">Wadsworth Center, New York State Department of Health, State University of New York, Albany, New York 12201</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York 12201</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">20934458</idno>
<idno type="pmc">2991506</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991506</idno>
<idno type="RBID">PMC:2991506</idno>
<idno type="doi">10.1016/j.vaccine.2010.08.106</idno>
<date when="2010">2010</date>
<idno type="wicri:Area/Pmc/Corpus">000560</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000560</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">NS-based Live Attenuated H1N1 Pandemic Vaccines Protect Mice and Ferrets</title>
<author><name sortKey="Zhou, Bin" sort="Zhou, Bin" uniqKey="Zhou B" first="Bin" last="Zhou">Bin Zhou</name>
<affiliation><nlm:aff id="A1">Wadsworth Center, New York State Department of Health, State University of New York, Albany, New York 12201</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York 12201</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name>
<affiliation><nlm:aff id="A1">Wadsworth Center, New York State Department of Health, State University of New York, Albany, New York 12201</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences (CAS), Wuhan, PR China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Belser, Jessica A" sort="Belser, Jessica A" uniqKey="Belser J" first="Jessica A." last="Belser">Jessica A. Belser</name>
<affiliation><nlm:aff id="A4">Immunology and Pathogenesis Branch, Influenza Division, NCIRD</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pearce, Melissa B" sort="Pearce, Melissa B" uniqKey="Pearce M" first="Melissa B." last="Pearce">Melissa B. Pearce</name>
<affiliation><nlm:aff id="A4">Immunology and Pathogenesis Branch, Influenza Division, NCIRD</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schmolke, Mirco" sort="Schmolke, Mirco" uniqKey="Schmolke M" first="Mirco" last="Schmolke">Mirco Schmolke</name>
<affiliation><nlm:aff id="A5">Department of Microbiology, Mount Sinai School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Subba, Anju X" sort="Subba, Anju X" uniqKey="Subba A" first="Anju X." last="Subba">Anju X. Subba</name>
<affiliation><nlm:aff id="A1">Wadsworth Center, New York State Department of Health, State University of New York, Albany, New York 12201</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Shi, Zhengli" sort="Shi, Zhengli" uniqKey="Shi Z" first="Zhengli" last="Shi">Zhengli Shi</name>
<affiliation><nlm:aff id="A3">State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences (CAS), Wuhan, PR China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zaki, Sherif R" sort="Zaki, Sherif R" uniqKey="Zaki S" first="Sherif R." last="Zaki">Sherif R. Zaki</name>
<affiliation><nlm:aff id="A6">Infectious Disease Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Blau, Dianna M" sort="Blau, Dianna M" uniqKey="Blau D" first="Dianna M." last="Blau">Dianna M. Blau</name>
<affiliation><nlm:aff id="A6">Infectious Disease Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name>
<affiliation><nlm:aff id="A5">Department of Microbiology, Mount Sinai School of Medicine, New York, New York</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A7">Institute of Global Health and Emerging Pathogens, Mount Sinai School of Medicine, New York, New York</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tumpey, Terrence M" sort="Tumpey, Terrence M" uniqKey="Tumpey T" first="Terrence M." last="Tumpey">Terrence M. Tumpey</name>
<affiliation><nlm:aff id="A4">Immunology and Pathogenesis Branch, Influenza Division, NCIRD</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wentworth, David E" sort="Wentworth, David E" uniqKey="Wentworth D" first="David E." last="Wentworth">David E. Wentworth</name>
<affiliation><nlm:aff id="A1">Wadsworth Center, New York State Department of Health, State University of New York, Albany, New York 12201</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York 12201</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Vaccine</title>
<idno type="ISSN">0264-410X</idno>
<idno type="eISSN">1873-2518</idno>
<imprint><date when="2010">2010</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P1">Although vaccines against influenza A virus are the most effective method to combat infection, it is clear that their production needs to be accelerated and their efficacy improved. We generated live attenuated human influenza A vaccines (LAIVs) by rationally engineering mutations directly into the genome of a pandemic-H1N1 virus. Two LAIVs (NS1-73 and NS1-126) were based on the success of LAIVs for animal influenza A viruses. A third candidate (NSΔ5) is a unique NS-mutant that has never been used as a LAIV. The vaccine potential of each LAIV was determined through analysis of attenuation, interferon production, immunogenicity, and their ability to protect mice and ferrets. This study demonstrates that NSΔ5 is an ideal LAIV candidate, provides important information on the effects that different NS mutations have on the pandemic-H1N1 virus and shows that LAIVs can be engineered directly from the genomes of emerging/circulating influenza A viruses.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8406899</journal-id>
<journal-id journal-id-type="pubmed-jr-id">7945</journal-id>
<journal-id journal-id-type="nlm-ta">Vaccine</journal-id>
<journal-title>Vaccine</journal-title>
<issn pub-type="ppub">0264-410X</issn>
<issn pub-type="epub">1873-2518</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">20934458</article-id>
<article-id pub-id-type="pmc">2991506</article-id>
<article-id pub-id-type="doi">10.1016/j.vaccine.2010.08.106</article-id>
<article-id pub-id-type="manuscript">NIHMS243658</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>NS-based Live Attenuated H1N1 Pandemic Vaccines Protect Mice and Ferrets</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Zhou</surname>
<given-names>Bin</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
<xref rid="FN2" ref-type="author-notes">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Yan</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A3" ref-type="aff">3</xref>
<xref rid="FN2" ref-type="author-notes">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Belser</surname>
<given-names>Jessica A.</given-names>
</name>
<xref rid="A4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pearce</surname>
<given-names>Melissa B.</given-names>
</name>
<xref rid="A4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schmolke</surname>
<given-names>Mirco</given-names>
</name>
<xref rid="A5" ref-type="aff">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Subba</surname>
<given-names>Anju X.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shi</surname>
<given-names>Zhengli</given-names>
</name>
<xref rid="A3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zaki</surname>
<given-names>Sherif R.</given-names>
</name>
<xref rid="A6" ref-type="aff">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Blau</surname>
<given-names>Dianna M.</given-names>
</name>
<xref rid="A6" ref-type="aff">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>García-Sastre</surname>
<given-names>Adolfo</given-names>
</name>
<xref rid="A5" ref-type="aff">5</xref>
<xref rid="A7" ref-type="aff">7</xref>
<xref rid="A8" ref-type="aff">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tumpey</surname>
<given-names>Terrence M.</given-names>
</name>
<xref rid="A4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wentworth</surname>
<given-names>David E.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Wadsworth Center, New York State Department of Health, State University of New York, Albany, New York 12201</aff>
<aff id="A2"><label>2</label>
Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York 12201</aff>
<aff id="A3"><label>3</label>
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences (CAS), Wuhan, PR China</aff>
<aff id="A4"><label>4</label>
Immunology and Pathogenesis Branch, Influenza Division, NCIRD</aff>
<aff id="A5"><label>5</label>
Department of Microbiology, Mount Sinai School of Medicine, New York, New York</aff>
<aff id="A6"><label>6</label>
Infectious Disease Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia</aff>
<aff id="A7"><label>7</label>
Institute of Global Health and Emerging Pathogens, Mount Sinai School of Medicine, New York, New York</aff>
<aff id="A8"><label>8</label>
Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, New York</aff>
<author-notes><corresp id="FN1"><label>*</label>
Corresponding Author: David E. Wentworth, PhD, Wadsworth Center, NYSDOH, Griffin Laboratory, 5668 State Farm Road, Slingerlands, NY 12159, Phone: 518-485-6730, Fax: 518-869-6487, <email>dew05@health.state.ny.us</email>
</corresp>
<fn id="FN2" fn-type="equal"><label>†</label>
<p>Contributed equally to this study.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>19</day>
<month>10</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="epub"><day>8</day>
<month>10</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="ppub"><day>23</day>
<month>11</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>23</day>
<month>11</month>
<year>2011</year>
</pub-date>
<volume>28</volume>
<issue>50</issue>
<fpage>8015</fpage>
<lpage>8025</lpage>
<abstract><p id="P1">Although vaccines against influenza A virus are the most effective method to combat infection, it is clear that their production needs to be accelerated and their efficacy improved. We generated live attenuated human influenza A vaccines (LAIVs) by rationally engineering mutations directly into the genome of a pandemic-H1N1 virus. Two LAIVs (NS1-73 and NS1-126) were based on the success of LAIVs for animal influenza A viruses. A third candidate (NSΔ5) is a unique NS-mutant that has never been used as a LAIV. The vaccine potential of each LAIV was determined through analysis of attenuation, interferon production, immunogenicity, and their ability to protect mice and ferrets. This study demonstrates that NSΔ5 is an ideal LAIV candidate, provides important information on the effects that different NS mutations have on the pandemic-H1N1 virus and shows that LAIVs can be engineered directly from the genomes of emerging/circulating influenza A viruses.</p>
</abstract>
<kwd-group><kwd>Influenza A virus</kwd>
<kwd>live attenuated vaccine</kwd>
<kwd>Nonstructural protein</kwd>
</kwd-group>
<contract-num rid="AI1">U54 AI057158-06
||AI</contract-num>
<contract-num rid="AI1">P01 AI059576-050005
||AI</contract-num>
<contract-sponsor id="AI1">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</contract-sponsor>
</article-meta>
</front>
</pmc>
</record>
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