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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A H5N1 cold-adapted vaccine virus</title>
<author><name sortKey="Suguitan, Amorsolo L" sort="Suguitan, Amorsolo L" uniqKey="Suguitan A" first="Amorsolo L." last="Suguitan">Amorsolo L. Suguitan</name>
<affiliation><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3203, Bethesda, Maryland, USA 20892-3203</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Marino, Michael P" sort="Marino, Michael P" uniqKey="Marino M" first="Michael P." last="Marino">Michael P. Marino</name>
<affiliation><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3203, Bethesda, Maryland, USA 20892-3203</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Desai, Purvi D" sort="Desai, Purvi D" uniqKey="Desai P" first="Purvi D." last="Desai">Purvi D. Desai</name>
<affiliation><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3203, Bethesda, Maryland, USA 20892-3203</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chen, Li Mei" sort="Chen, Li Mei" uniqKey="Chen L" first="Li-Mei" last="Chen">Li-Mei Chen</name>
<affiliation><nlm:aff id="A2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, USA 30333</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Matsuoka, Yumiko" sort="Matsuoka, Yumiko" uniqKey="Matsuoka Y" first="Yumiko" last="Matsuoka">Yumiko Matsuoka</name>
<affiliation><nlm:aff id="A2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, USA 30333</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Donis, Ruben O" sort="Donis, Ruben O" uniqKey="Donis R" first="Ruben O." last="Donis">Ruben O. Donis</name>
<affiliation><nlm:aff id="A2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, USA 30333</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jin, Hong" sort="Jin, Hong" uniqKey="Jin H" first="Hong" last="Jin">Hong Jin</name>
<affiliation><nlm:aff id="A3">MedImmune, 297 N Bernardo Avenue, Mountain View, California, USA 94043</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Swayne, David E" sort="Swayne, David E" uniqKey="Swayne D" first="David E." last="Swayne">David E. Swayne</name>
<affiliation><nlm:aff id="A4">Southeast Poultry Research Laboratory, US Department of Agriculture, Agricultural Research Service, 934 College Station Road, Athens, Georgia, USA 30605</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kemble, George" sort="Kemble, George" uniqKey="Kemble G" first="George" last="Kemble">George Kemble</name>
<affiliation><nlm:aff id="A3">MedImmune, 297 N Bernardo Avenue, Mountain View, California, USA 94043</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name>
<affiliation><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3203, Bethesda, Maryland, USA 20892-3203</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">19833372</idno>
<idno type="pmc">2787913</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787913</idno>
<idno type="RBID">PMC:2787913</idno>
<idno type="doi">10.1016/j.virol.2009.09.017</idno>
<date when="2009">2009</date>
<idno type="wicri:Area/Pmc/Corpus">000522</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000522</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A H5N1 cold-adapted vaccine virus</title>
<author><name sortKey="Suguitan, Amorsolo L" sort="Suguitan, Amorsolo L" uniqKey="Suguitan A" first="Amorsolo L." last="Suguitan">Amorsolo L. Suguitan</name>
<affiliation><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3203, Bethesda, Maryland, USA 20892-3203</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Marino, Michael P" sort="Marino, Michael P" uniqKey="Marino M" first="Michael P." last="Marino">Michael P. Marino</name>
<affiliation><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3203, Bethesda, Maryland, USA 20892-3203</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Desai, Purvi D" sort="Desai, Purvi D" uniqKey="Desai P" first="Purvi D." last="Desai">Purvi D. Desai</name>
<affiliation><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3203, Bethesda, Maryland, USA 20892-3203</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chen, Li Mei" sort="Chen, Li Mei" uniqKey="Chen L" first="Li-Mei" last="Chen">Li-Mei Chen</name>
<affiliation><nlm:aff id="A2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, USA 30333</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Matsuoka, Yumiko" sort="Matsuoka, Yumiko" uniqKey="Matsuoka Y" first="Yumiko" last="Matsuoka">Yumiko Matsuoka</name>
<affiliation><nlm:aff id="A2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, USA 30333</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Donis, Ruben O" sort="Donis, Ruben O" uniqKey="Donis R" first="Ruben O." last="Donis">Ruben O. Donis</name>
<affiliation><nlm:aff id="A2">Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, USA 30333</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jin, Hong" sort="Jin, Hong" uniqKey="Jin H" first="Hong" last="Jin">Hong Jin</name>
<affiliation><nlm:aff id="A3">MedImmune, 297 N Bernardo Avenue, Mountain View, California, USA 94043</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Swayne, David E" sort="Swayne, David E" uniqKey="Swayne D" first="David E." last="Swayne">David E. Swayne</name>
<affiliation><nlm:aff id="A4">Southeast Poultry Research Laboratory, US Department of Agriculture, Agricultural Research Service, 934 College Station Road, Athens, Georgia, USA 30605</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kemble, George" sort="Kemble, George" uniqKey="Kemble G" first="George" last="Kemble">George Kemble</name>
<affiliation><nlm:aff id="A3">MedImmune, 297 N Bernardo Avenue, Mountain View, California, USA 94043</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name>
<affiliation><nlm:aff id="A1">Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3203, Bethesda, Maryland, USA 20892-3203</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Virology</title>
<idno type="ISSN">0042-6822</idno>
<idno type="eISSN">1096-0341</idno>
<imprint><date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P4">A recombinant live attenuated influenza virus ΔH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA <italic>ca</italic>
) virus was previously shown to be attenuated in chickens, mice and ferrets. Evaluation of the recombinant H5N1 viruses in mice indicated that three independent factors contributed to the attenuation of the ΔH5N1 vaccine: the attenuating mutations specified by the AA <italic>ca</italic>
loci had the greatest influence, followed by the deletion of the H5 HA multi-basic cleavage site (MBS), and the constellation effects of the AA genes acting in concert with the H5N1 glycoproteins. Restoring the MBS in the H5 HA of the vaccine virus improved its immunogenicity and efficacy, likely as a consequence of increased virus replication, indicating that removal of the MBS had a deleterious effect on the immunogenicity and efficacy of the ΔH5N1 vaccine in mice.</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">0110674</journal-id>
<journal-id journal-id-type="pubmed-jr-id">8015</journal-id>
<journal-id journal-id-type="nlm-ta">Virology</journal-id>
<journal-title>Virology</journal-title>
<issn pub-type="ppub">0042-6822</issn>
<issn pub-type="epub">1096-0341</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">19833372</article-id>
<article-id pub-id-type="pmc">2787913</article-id>
<article-id pub-id-type="doi">10.1016/j.virol.2009.09.017</article-id>
<article-id pub-id-type="manuscript">NIHMS147646</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A H5N1 cold-adapted vaccine virus</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Suguitan</surname>
<given-names>Amorsolo L.</given-names>
<suffix>Jr.</suffix>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="author-notes" rid="FN1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Marino</surname>
<given-names>Michael P.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="author-notes" rid="FN2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Desai</surname>
<given-names>Purvi D.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chen</surname>
<given-names>Li-Mei</given-names>
</name>
<xref ref-type="aff" rid="A2">b</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Matsuoka</surname>
<given-names>Yumiko</given-names>
</name>
<xref ref-type="aff" rid="A2">b</xref>
<xref ref-type="author-notes" rid="FN3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Donis</surname>
<given-names>Ruben O.</given-names>
</name>
<xref ref-type="aff" rid="A2">b</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jin</surname>
<given-names>Hong</given-names>
</name>
<xref ref-type="aff" rid="A3">c</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Swayne</surname>
<given-names>David E.</given-names>
</name>
<xref ref-type="aff" rid="A4">d</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kemble</surname>
<given-names>George</given-names>
</name>
<xref ref-type="aff" rid="A3">c</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Subbarao</surname>
<given-names>Kanta</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>a</label>
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3203, Bethesda, Maryland, USA 20892-3203</aff>
<aff id="A2"><label>b</label>
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, USA 30333</aff>
<aff id="A3"><label>c</label>
MedImmune, 297 N Bernardo Avenue, Mountain View, California, USA 94043</aff>
<aff id="A4"><label>d</label>
Southeast Poultry Research Laboratory, US Department of Agriculture, Agricultural Research Service, 934 College Station Road, Athens, Georgia, USA 30605</aff>
<author-notes><fn fn-type="current-aff" id="FN1"><label>1</label>
<p id="P1">Amorsolo L. Suguitan, Jr. – MedImmune, 297 N Bernardo Avenue, Mountain View, CA 95054</p>
</fn>
<fn fn-type="current-aff" id="FN2"><label>2</label>
<p id="P2">Michael P. Marino – Center for Biologics Evaluation and Research Office of Cellular, Tissue and Gene Therapies Division of Cell and Gene Therapies Food and Drug Administration, Bldg 29B, Rm 1G11 8800 Rockville Pike, Bethesda, MD 20892 USA</p>
</fn>
<fn fn-type="current-aff" id="FN3"><label>3</label>
<p id="P3">Yumiko Matsuoka – Laboratory of Infectious Diseases National Institute of Allergy and Infectious Diseases National Institutes of Health 33 North Drive, Bldg 33, Rm 3E13C.4, MSC 3203 Bethesda, MD 20892 USA</p>
</fn>
<corresp id="CR1"><underline>Corresponding Author:</underline>
Dr. Kanta Subbarao LID, NIAID, NIH Rm 3E13C.1, MSC 3203, 33 North Drive, Bethesda, MD 20892 Tel. (1-301) 451-3839 Fax (1-301) 480-5719 <email>ksubbarao@niaid.nih.gov</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>24</day>
<month>9</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="epub"><day>14</day>
<month>10</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="ppub"><day>20</day>
<month>12</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>20</day>
<month>12</month>
<year>2010</year>
</pub-date>
<volume>395</volume>
<issue>2</issue>
<fpage>280</fpage>
<lpage>288</lpage>
<permissions><copyright-statement>© 2009 Published by Elsevier Inc.</copyright-statement>
<copyright-year>2009</copyright-year>
</permissions>
<abstract><p id="P4">A recombinant live attenuated influenza virus ΔH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA <italic>ca</italic>
) virus was previously shown to be attenuated in chickens, mice and ferrets. Evaluation of the recombinant H5N1 viruses in mice indicated that three independent factors contributed to the attenuation of the ΔH5N1 vaccine: the attenuating mutations specified by the AA <italic>ca</italic>
loci had the greatest influence, followed by the deletion of the H5 HA multi-basic cleavage site (MBS), and the constellation effects of the AA genes acting in concert with the H5N1 glycoproteins. Restoring the MBS in the H5 HA of the vaccine virus improved its immunogenicity and efficacy, likely as a consequence of increased virus replication, indicating that removal of the MBS had a deleterious effect on the immunogenicity and efficacy of the ΔH5N1 vaccine in mice.</p>
</abstract>
<kwd-group><kwd>influenza</kwd>
<kwd>H5N1</kwd>
<kwd>HA cleavability</kwd>
<kwd>attenuation</kwd>
<kwd>pandemic</kwd>
<kwd>immunogenicity</kwd>
<kwd>A/VietNam/1203/04</kwd>
<kwd>live vaccine</kwd>
<kwd>multi-basic cleavage site</kwd>
</kwd-group>
<contract-num rid="AI1">Z01 AI000933-05
||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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