In Vitro Neutralization Is Not Predictive of Prophylactic Efficacy of Broadly Neutralizing Monoclonal Antibodies CR6261 and CR9114 against Lethal H2 Influenza Virus Challenge in Mice
Identifieur interne : 000701 ( Pmc/Curation ); précédent : 000700; suivant : 000702In Vitro Neutralization Is Not Predictive of Prophylactic Efficacy of Broadly Neutralizing Monoclonal Antibodies CR6261 and CR9114 against Lethal H2 Influenza Virus Challenge in Mice
Auteurs : Troy C. Sutton [États-Unis] ; Elaine W. Lamirande [États-Unis] ; Kevin W. Bock [États-Unis] ; Ian N. Moore [États-Unis] ; Wouter Koudstaal [Pays-Bas] ; Muniza Rehman [Pays-Bas] ; Gerrit Jan Weverling [Pays-Bas] ; Jaap Goudsmit [Pays-Bas] ; Kanta Subbarao [États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 2017.
Abstract
Influenza viruses of the H1N1, H2N2, and H3N2 subtypes have caused previous pandemics. H2 influenza viruses represent a pandemic threat due to continued circulation in wild birds and limited immunity in the human population. In the event of a pandemic, antiviral agents are the mainstay for treatment, but broadly neutralizing antibodies (bNAbs) may be a viable alternative for short-term prophylaxis or treatment. The hemagglutinin stem binding bNAbs CR6261 and CR9114 have been shown to protect mice from severe disease following challenge with H1N1 and H5N1 and with H1N1, H3N2, and influenza B viruses, respectively. Early studies with CR6261 and CR9114 showed weak
Url:
DOI: 10.1128/JVI.01603-17
PubMed: 29046448
PubMed Central: 5709608
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000701
Links to Exploration step
PMC:5709608Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>In Vitro</italic> Neutralization Is Not Predictive of Prophylactic Efficacy of Broadly Neutralizing Monoclonal Antibodies CR6261 and CR9114 against Lethal H2 Influenza Virus Challenge in Mice</title><author><name sortKey="Sutton, Troy C" sort="Sutton, Troy C" uniqKey="Sutton T" first="Troy C." last="Sutton">Troy C. Sutton</name><affiliation wicri:level="1"><nlm:aff id="aff1">Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Lamirande, Elaine W" sort="Lamirande, Elaine W" uniqKey="Lamirande E" first="Elaine W." last="Lamirande">Elaine W. Lamirande</name><affiliation wicri:level="1"><nlm:aff id="aff1">Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Bock, Kevin W" sort="Bock, Kevin W" uniqKey="Bock K" first="Kevin W." last="Bock">Kevin W. Bock</name><affiliation wicri:level="1"><nlm:aff id="aff2">Comparative Medicine Branch, Infectious Disease Pathogenesis Section, NIAID, NIH, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Comparative Medicine Branch, Infectious Disease Pathogenesis Section, NIAID, NIH, Bethesda, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Moore, Ian N" sort="Moore, Ian N" uniqKey="Moore I" first="Ian N." last="Moore">Ian N. Moore</name><affiliation wicri:level="1"><nlm:aff id="aff2">Comparative Medicine Branch, Infectious Disease Pathogenesis Section, NIAID, NIH, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Comparative Medicine Branch, Infectious Disease Pathogenesis Section, NIAID, NIH, Bethesda, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Koudstaal, Wouter" sort="Koudstaal, Wouter" uniqKey="Koudstaal W" first="Wouter" last="Koudstaal">Wouter Koudstaal</name><affiliation wicri:level="1"><nlm:aff id="aff3">Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Rehman, Muniza" sort="Rehman, Muniza" uniqKey="Rehman M" first="Muniza" last="Rehman">Muniza Rehman</name><affiliation wicri:level="1"><nlm:aff id="aff3">Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Weverling, Gerrit Jan" sort="Weverling, Gerrit Jan" uniqKey="Weverling G" first="Gerrit Jan" last="Weverling">Gerrit Jan Weverling</name><affiliation wicri:level="1"><nlm:aff id="aff3">Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Goudsmit, Jaap" sort="Goudsmit, Jaap" uniqKey="Goudsmit J" first="Jaap" last="Goudsmit">Jaap Goudsmit</name><affiliation wicri:level="1"><nlm:aff id="aff3">Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><affiliation wicri:level="1"><nlm:aff id="aff1">Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29046448</idno><idno type="pmc">5709608</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709608</idno><idno type="RBID">PMC:5709608</idno><idno type="doi">10.1128/JVI.01603-17</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">000701</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000701</idno><idno type="wicri:Area/Pmc/Curation">000701</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000701</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>In Vitro</italic> Neutralization Is Not Predictive of Prophylactic Efficacy of Broadly Neutralizing Monoclonal Antibodies CR6261 and CR9114 against Lethal H2 Influenza Virus Challenge in Mice</title><author><name sortKey="Sutton, Troy C" sort="Sutton, Troy C" uniqKey="Sutton T" first="Troy C." last="Sutton">Troy C. Sutton</name><affiliation wicri:level="1"><nlm:aff id="aff1">Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Lamirande, Elaine W" sort="Lamirande, Elaine W" uniqKey="Lamirande E" first="Elaine W." last="Lamirande">Elaine W. Lamirande</name><affiliation wicri:level="1"><nlm:aff id="aff1">Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Bock, Kevin W" sort="Bock, Kevin W" uniqKey="Bock K" first="Kevin W." last="Bock">Kevin W. Bock</name><affiliation wicri:level="1"><nlm:aff id="aff2">Comparative Medicine Branch, Infectious Disease Pathogenesis Section, NIAID, NIH, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Comparative Medicine Branch, Infectious Disease Pathogenesis Section, NIAID, NIH, Bethesda, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Moore, Ian N" sort="Moore, Ian N" uniqKey="Moore I" first="Ian N." last="Moore">Ian N. Moore</name><affiliation wicri:level="1"><nlm:aff id="aff2">Comparative Medicine Branch, Infectious Disease Pathogenesis Section, NIAID, NIH, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Comparative Medicine Branch, Infectious Disease Pathogenesis Section, NIAID, NIH, Bethesda, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Koudstaal, Wouter" sort="Koudstaal, Wouter" uniqKey="Koudstaal W" first="Wouter" last="Koudstaal">Wouter Koudstaal</name><affiliation wicri:level="1"><nlm:aff id="aff3">Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Rehman, Muniza" sort="Rehman, Muniza" uniqKey="Rehman M" first="Muniza" last="Rehman">Muniza Rehman</name><affiliation wicri:level="1"><nlm:aff id="aff3">Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Weverling, Gerrit Jan" sort="Weverling, Gerrit Jan" uniqKey="Weverling G" first="Gerrit Jan" last="Weverling">Gerrit Jan Weverling</name><affiliation wicri:level="1"><nlm:aff id="aff3">Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Goudsmit, Jaap" sort="Goudsmit, Jaap" uniqKey="Goudsmit J" first="Jaap" last="Goudsmit">Jaap Goudsmit</name><affiliation wicri:level="1"><nlm:aff id="aff3">Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><affiliation wicri:level="1"><nlm:aff id="aff1">Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><p>Influenza viruses of the H1N1, H2N2, and H3N2 subtypes have caused previous pandemics. H2 influenza viruses represent a pandemic threat due to continued circulation in wild birds and limited immunity in the human population. In the event of a pandemic, antiviral agents are the mainstay for treatment, but broadly neutralizing antibodies (bNAbs) may be a viable alternative for short-term prophylaxis or treatment. The hemagglutinin stem binding bNAbs CR6261 and CR9114 have been shown to protect mice from severe disease following challenge with H1N1 and H5N1 and with H1N1, H3N2, and influenza B viruses, respectively. Early studies with CR6261 and CR9114 showed weak <italic>in vitro</italic> activity against human H2 influenza viruses, but the <italic>in vivo</italic> efficacy against H2 viruses is unknown. Therefore, we evaluated these antibodies against human- and animal-origin H2 viruses A/Ann Arbor/6/1960 (H2N2) (AA60) and A/swine/MO/4296424/06 (H2N3) (Sw06). <italic>In vitro</italic>, CR6261 neutralized both H2 viruses, while CR9114 only neutralized Sw06. To evaluate prophylactic efficacy, mice were given CR6261 or CR9114 and intranasally challenged 24 h later with lethal doses of AA60 or Sw06. Both antibodies reduced mortality, weight loss, airway inflammation, and pulmonary viral load. Using engineered bNAb variants, antibody-mediated cell cytotoxicity reporter assays, and Fcγ receptor-deficient (<italic>Fcer1g</italic><sup>−/−</sup>) mice, we show that the <italic>in vivo</italic> efficacy of CR9114 against AA60 is mediated by Fcγ receptor-dependent mechanisms. Collectively, these findings demonstrate the <italic>in vivo</italic> efficacy of CR6261 and CR9114 against H2 viruses and emphasize the need for <italic>in vivo</italic> evaluation of bNAbs.</p><p><bold>IMPORTANCE</bold> bNAbs represent a strategy to prevent or treat infection by a wide range of influenza viruses. The evaluation of these antibodies against H2 viruses is important because H2 viruses caused a pandemic in 1957 and could cross into humans again. We demonstrate that CR6261 and CR9114 are effective against infection with H2 viruses of both human and animal origin in mice, despite the finding that CR9114 did not display <italic>in vitro</italic> neutralizing activity against the human H2 virus. These findings emphasize the importance of <italic>in vivo</italic> evaluation and testing of bNAbs.</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">J Virol</journal-id><journal-id journal-id-type="iso-abbrev">J. Virol</journal-id><journal-id journal-id-type="hwp">jvi</journal-id><journal-id journal-id-type="pmc">jvi</journal-id><journal-id journal-id-type="publisher-id">JVI</journal-id><journal-title-group><journal-title>Journal of Virology</journal-title></journal-title-group><issn pub-type="ppub">0022-538X</issn><issn pub-type="epub">1098-5514</issn><publisher><publisher-name>American Society for Microbiology</publisher-name><publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">29046448</article-id><article-id pub-id-type="pmc">5709608</article-id><article-id pub-id-type="publisher-id">01603-17</article-id><article-id pub-id-type="doi">10.1128/JVI.01603-17</article-id><article-categories><subj-group subj-group-type="heading"><subject>Vaccines and Antiviral Agents</subject></subj-group></article-categories><title-group><article-title><italic>In Vitro</italic> Neutralization Is Not Predictive of Prophylactic Efficacy of Broadly Neutralizing Monoclonal Antibodies CR6261 and CR9114 against Lethal H2 Influenza Virus Challenge in Mice</article-title><alt-title alt-title-type="running-head">Antibody Protection against H2 Influenza</alt-title><alt-title alt-title-type="short-authors">Sutton et al.</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Sutton</surname><given-names>Troy C.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Lamirande</surname><given-names>Elaine W.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bock</surname><given-names>Kevin W.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Moore</surname><given-names>Ian N.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Koudstaal</surname><given-names>Wouter</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rehman</surname><given-names>Muniza</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Weverling</surname><given-names>Gerrit Jan</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Goudsmit</surname><given-names>Jaap</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Subbarao</surname><given-names>Kanta</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="author-notes" rid="fn1">*</xref></contrib><aff id="aff1"><label>a</label>Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA</aff><aff id="aff2"><label>b</label>Comparative Medicine Branch, Infectious Disease Pathogenesis Section, NIAID, NIH, Bethesda, Maryland, USA</aff><aff id="aff3"><label>c</label>Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden, the Netherlands</aff></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>García-Sastre</surname><given-names>Adolfo</given-names></name><role>Editor</role><aff>Icahn School of Medicine at Mount Sinai</aff></contrib></contrib-group><author-notes><corresp id="cor1">Address correspondence to Kanta Subbarao, <email>ksubbarao@niaid.nih.gov</email>.</corresp><fn id="fn1" fn-type="present-address"><label>*</label><p>Present address: Troy C. Sutton, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, The Huck Institutes of Life Sciences, University Park, Pennsylvania, USA; Jaap Goudsmit, Department of Epidemiology, T.H. Chan School of Public Health, Harvard University, Boston, Massachussetts, USA; Kanta Subbarao, WHO Collaborating Centre for Reference and Research on Influenza and University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.</p></fn><fn fn-type="other"><p><bold>Citation</bold> Sutton TC, Lamirande EW, Bock KW, Moore IN, Koudstaal W, Rehman M, Weverling GJ, Goudsmit J, Subbarao K. 2017. <italic>In vitro</italic> neutralization is not predictive of prophylactic efficacy of broadly neutralizing monoclonal antibodies CR6261 and CR9114 against lethal H2 influenza virus challenge in mice. J Virol 91:e01603-17. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/JVI.01603-17">https://doi.org/10.1128/JVI.01603-17</ext-link>.</p></fn></author-notes><pub-date pub-type="epreprint"><day>18</day><month>10</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>30</day><month>11</month><year>2017</year></pub-date><pub-date pub-type="collection"><day>15</day><month>12</month><year>2017</year></pub-date><volume>91</volume><issue>24</issue><elocation-id>e01603-17</elocation-id><history><date date-type="received"><day>11</day><month>9</month><year>2017</year></date><date date-type="accepted"><day>12</day><month>9</month><year>2017</year></date></history><permissions><copyright-statement>Copyright © 2017 American Society for Microbiology.</copyright-statement><copyright-year>2017</copyright-year><copyright-holder>American Society for Microbiology</copyright-holder><license license-type="asm" xlink:href="https://doi.org/10.1128/ASMCopyrightv2"><license-p><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/ASMCopyrightv2">All Rights Reserved</ext-link>.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="zjv024173113001.pdf"></self-uri><abstract><title>ABSTRACT</title><p>Influenza viruses of the H1N1, H2N2, and H3N2 subtypes have caused previous pandemics. H2 influenza viruses represent a pandemic threat due to continued circulation in wild birds and limited immunity in the human population. In the event of a pandemic, antiviral agents are the mainstay for treatment, but broadly neutralizing antibodies (bNAbs) may be a viable alternative for short-term prophylaxis or treatment. The hemagglutinin stem binding bNAbs CR6261 and CR9114 have been shown to protect mice from severe disease following challenge with H1N1 and H5N1 and with H1N1, H3N2, and influenza B viruses, respectively. Early studies with CR6261 and CR9114 showed weak <italic>in vitro</italic> activity against human H2 influenza viruses, but the <italic>in vivo</italic> efficacy against H2 viruses is unknown. Therefore, we evaluated these antibodies against human- and animal-origin H2 viruses A/Ann Arbor/6/1960 (H2N2) (AA60) and A/swine/MO/4296424/06 (H2N3) (Sw06). <italic>In vitro</italic>, CR6261 neutralized both H2 viruses, while CR9114 only neutralized Sw06. To evaluate prophylactic efficacy, mice were given CR6261 or CR9114 and intranasally challenged 24 h later with lethal doses of AA60 or Sw06. Both antibodies reduced mortality, weight loss, airway inflammation, and pulmonary viral load. Using engineered bNAb variants, antibody-mediated cell cytotoxicity reporter assays, and Fcγ receptor-deficient (<italic>Fcer1g</italic><sup>−/−</sup>) mice, we show that the <italic>in vivo</italic> efficacy of CR9114 against AA60 is mediated by Fcγ receptor-dependent mechanisms. Collectively, these findings demonstrate the <italic>in vivo</italic> efficacy of CR6261 and CR9114 against H2 viruses and emphasize the need for <italic>in vivo</italic> evaluation of bNAbs.</p><p><bold>IMPORTANCE</bold> bNAbs represent a strategy to prevent or treat infection by a wide range of influenza viruses. The evaluation of these antibodies against H2 viruses is important because H2 viruses caused a pandemic in 1957 and could cross into humans again. We demonstrate that CR6261 and CR9114 are effective against infection with H2 viruses of both human and animal origin in mice, despite the finding that CR9114 did not display <italic>in vitro</italic> neutralizing activity against the human H2 virus. These findings emphasize the importance of <italic>in vivo</italic> evaluation and testing of bNAbs.</p></abstract><kwd-group><title>KEYWORDS</title><kwd>H2 influenza virus</kwd><kwd>broadly neutralizing antibodies</kwd><kwd>prophylaxis</kwd><kwd><italic>in vivo</italic> evaluation</kwd><kwd>antibody function</kwd><kwd>influenza</kwd><kwd>influenza vaccines</kwd></kwd-group><funding-group><award-group id="award1"><funding-source id="gs1">NIAID Intramural Research Program</funding-source><principal-award-recipient>Troy C. Sutton</principal-award-recipient><principal-award-recipient>Elaine Lamirande</principal-award-recipient><principal-award-recipient>Kevin W. Bock</principal-award-recipient><principal-award-recipient>Ian N. Moore</principal-award-recipient><principal-award-recipient>Kanta Subbarao</principal-award-recipient></award-group></funding-group><counts><fig-count count="7"></fig-count><table-count count="1"></table-count><equation-count count="0"></equation-count><ref-count count="26"></ref-count><page-count count="12"></page-count><word-count count="6913"></word-count></counts><custom-meta-group><custom-meta><meta-name>cover-date</meta-name><meta-value>December 2017</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/H2N2V1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000701 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000701 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= H2N2V1
|flux= Pmc
|étape= Curation
|type= RBID
|clé= PMC:5709608
|texte= In Vitro Neutralization Is Not Predictive of Prophylactic Efficacy of Broadly Neutralizing Monoclonal Antibodies CR6261 and CR9114 against Lethal H2 Influenza Virus Challenge in Mice
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:29046448" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \
| NlmPubMed2Wicri -a H2N2V1
| This area was generated with Dilib version V0.6.33. |  |