Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure
Identifieur interne : 000897 ( Ncbi/Merge ); précédent : 000896; suivant : 000898Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure
Auteurs : Stephen S. H. Huang [Canada] ; Zhen Lin [Canada, République populaire de Chine] ; David Banner [Canada] ; Alberto J. Le N [Canada, République populaire de Chine] ; Stéphane G. Paquette [Canada] ; Barry Rubin [Canada] ; Salvatore Rubino [Italie] ; Yi Guan [République populaire de Chine] ; David J. Kelvin [Canada, Italie, République populaire de Chine] ; Alyson A. Kelvin [Canada]Source :
- Scientific Reports [ 2045-2322 ] ; 2013.
Abstract
Evolution of H1N1 influenza A outbreaks of the past 100 years is interesting and significantly complex and details of H1N1 genetic drift remains unknown. Here we investigated the clinical characteristics and immune cross-reactivity of significant historical H1N1 strains. We infected ferrets with H1N1 strains from 1943, 1947, 1977, 1986, 1999, and 2009 and showed each produced a unique clinical signature. We found significant cross-reactivity between viruses with similar HA sequences. Interestingly, A/FortMonmouth/1/1947 antisera cross-reacted with A/USSR/90/1977 virus, thought to be a 1947 resurfaced virus. Importantly, our immunological data that didn't show cross-reactivity can be extrapolated to failure of past H1N1 influenza vaccines, ie. 1947, 1986 and 2009. Together, our results help to elucidate H1N1 immuno-genetic alterations that occurred in the past 100 years and immune responses caused by H1N1 evolution. This work will facilitate development of future influenza therapeutics and prophylactics such as influenza vaccines.
Url:
DOI: 10.1038/srep01698
PubMed: 23608887
PubMed Central: 3633051
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000005
- to stream Pmc, to step Curation: 000005
- to stream Pmc, to step Checkpoint: 000616
Links to Exploration step
PMC:3633051Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure</title><author><name sortKey="Huang, Stephen S H" sort="Huang, Stephen S H" uniqKey="Huang S" first="Stephen S. H." last="Huang">Stephen S. H. Huang</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Immunology, Faculty of Medicine, University of Toronto</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation><nlm:aff id="a8">These authors contributed equally to this work.</nlm:aff></affiliation></author><author><name sortKey="Lin, Zhen" sort="Lin, Zhen" uniqKey="Lin Z" first="Zhen" last="Lin">Zhen Lin</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a5"><institution>International Institute of Infection and Immunity, Shantou University Medical College</institution>, Shantou, Guangdong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>, Shantou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation><affiliation><nlm:aff id="a8">These authors contributed equally to this work.</nlm:aff></affiliation></author><author><name sortKey="Banner, David" sort="Banner, David" uniqKey="Banner D" first="David" last="Banner">David Banner</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Le N, Alberto J" sort="Le N, Alberto J" uniqKey="Le N A" first="Alberto J." last="Le N">Alberto J. Le N</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a5"><institution>International Institute of Infection and Immunity, Shantou University Medical College</institution>, Shantou, Guangdong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>, Shantou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Paquette, Stephane G" sort="Paquette, Stephane G" uniqKey="Paquette S" first="Stéphane G." last="Paquette">Stéphane G. Paquette</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Institute of Medical Science, Faculty of Medicine, University of Toronto</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Rubin, Barry" sort="Rubin, Barry" uniqKey="Rubin B" first="Barry" last="Rubin">Barry Rubin</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Division of Vascular Surgery, Peter Munk Cardiac Centre, Toronto General Hospital Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Rubino, Salvatore" sort="Rubino, Salvatore" uniqKey="Rubino S" first="Salvatore" last="Rubino">Salvatore Rubino</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Universita' degli Studi di Sassari, Sezione di Microbiologia Sperimentale e Clinica</institution>, Dipartimento di Scienze Biomediche, Viale San Pietro 43/b, 07100 Sassari, Italia</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>, Dipartimento di Scienze Biomediche, Viale San Pietro 43/b, 07100 Sassari</wicri:regionArea><wicri:noRegion>07100 Sassari</wicri:noRegion></affiliation></author><author><name sortKey="Guan, Yi" sort="Guan, Yi" uniqKey="Guan Y" first="Yi" last="Guan">Yi Guan</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>International Institute of Infection and Immunity, Shantou University Medical College</institution>, Shantou, Guangdong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>, Shantou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Immunology, Faculty of Medicine, University of Toronto</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Universita' degli Studi di Sassari, Sezione di Microbiologia Sperimentale e Clinica</institution>, Dipartimento di Scienze Biomediche, Viale San Pietro 43/b, 07100 Sassari, Italia</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>, Dipartimento di Scienze Biomediche, Viale San Pietro 43/b, 07100 Sassari</wicri:regionArea><wicri:noRegion>07100 Sassari</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a5"><institution>International Institute of Infection and Immunity, Shantou University Medical College</institution>, Shantou, Guangdong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>, Shantou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Institute of Medical Science, Faculty of Medicine, University of Toronto</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Kelvin, Alyson A" sort="Kelvin, Alyson A" uniqKey="Kelvin A" first="Alyson A." last="Kelvin">Alyson A. Kelvin</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Immune Diagnostics & Research</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23608887</idno><idno type="pmc">3633051</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633051</idno><idno type="RBID">PMC:3633051</idno><idno type="doi">10.1038/srep01698</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000005</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000005</idno><idno type="wicri:Area/Pmc/Curation">000005</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000005</idno><idno type="wicri:Area/Pmc/Checkpoint">000616</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000616</idno><idno type="wicri:Area/Ncbi/Merge">000897</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure</title><author><name sortKey="Huang, Stephen S H" sort="Huang, Stephen S H" uniqKey="Huang S" first="Stephen S. H." last="Huang">Stephen S. H. Huang</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Immunology, Faculty of Medicine, University of Toronto</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation><nlm:aff id="a8">These authors contributed equally to this work.</nlm:aff></affiliation></author><author><name sortKey="Lin, Zhen" sort="Lin, Zhen" uniqKey="Lin Z" first="Zhen" last="Lin">Zhen Lin</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a5"><institution>International Institute of Infection and Immunity, Shantou University Medical College</institution>, Shantou, Guangdong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>, Shantou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation><affiliation><nlm:aff id="a8">These authors contributed equally to this work.</nlm:aff></affiliation></author><author><name sortKey="Banner, David" sort="Banner, David" uniqKey="Banner D" first="David" last="Banner">David Banner</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Le N, Alberto J" sort="Le N, Alberto J" uniqKey="Le N A" first="Alberto J." last="Le N">Alberto J. Le N</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a5"><institution>International Institute of Infection and Immunity, Shantou University Medical College</institution>, Shantou, Guangdong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>, Shantou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Paquette, Stephane G" sort="Paquette, Stephane G" uniqKey="Paquette S" first="Stéphane G." last="Paquette">Stéphane G. Paquette</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Institute of Medical Science, Faculty of Medicine, University of Toronto</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Rubin, Barry" sort="Rubin, Barry" uniqKey="Rubin B" first="Barry" last="Rubin">Barry Rubin</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Division of Vascular Surgery, Peter Munk Cardiac Centre, Toronto General Hospital Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Rubino, Salvatore" sort="Rubino, Salvatore" uniqKey="Rubino S" first="Salvatore" last="Rubino">Salvatore Rubino</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Universita' degli Studi di Sassari, Sezione di Microbiologia Sperimentale e Clinica</institution>, Dipartimento di Scienze Biomediche, Viale San Pietro 43/b, 07100 Sassari, Italia</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>, Dipartimento di Scienze Biomediche, Viale San Pietro 43/b, 07100 Sassari</wicri:regionArea><wicri:noRegion>07100 Sassari</wicri:noRegion></affiliation></author><author><name sortKey="Guan, Yi" sort="Guan, Yi" uniqKey="Guan Y" first="Yi" last="Guan">Yi Guan</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>International Institute of Infection and Immunity, Shantou University Medical College</institution>, Shantou, Guangdong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>, Shantou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Immunology, Faculty of Medicine, University of Toronto</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Universita' degli Studi di Sassari, Sezione di Microbiologia Sperimentale e Clinica</institution>, Dipartimento di Scienze Biomediche, Viale San Pietro 43/b, 07100 Sassari, Italia</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>, Dipartimento di Scienze Biomediche, Viale San Pietro 43/b, 07100 Sassari</wicri:regionArea><wicri:noRegion>07100 Sassari</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a5"><institution>International Institute of Infection and Immunity, Shantou University Medical College</institution>, Shantou, Guangdong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>, Shantou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Institute of Medical Science, Faculty of Medicine, University of Toronto</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Kelvin, Alyson A" sort="Kelvin, Alyson A" uniqKey="Kelvin A" first="Alyson A." last="Kelvin">Alyson A. Kelvin</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Immune Diagnostics & Research</institution>, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</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>Evolution of H1N1 influenza A outbreaks of the past 100 years is interesting and significantly complex and details of H1N1 genetic drift remains unknown. Here we investigated the clinical characteristics and immune cross-reactivity of significant historical H1N1 strains. We infected ferrets with H1N1 strains from 1943, 1947, 1977, 1986, 1999, and 2009 and showed each produced a unique clinical signature. We found significant cross-reactivity between viruses with similar HA sequences. Interestingly, A/FortMonmouth/1/1947 antisera cross-reacted with A/USSR/90/1977 virus, thought to be a 1947 resurfaced virus. Importantly, our immunological data that didn't show cross-reactivity can be extrapolated to failure of past H1N1 influenza vaccines, ie. 1947, 1986 and 2009. Together, our results help to elucidate H1N1 immuno-genetic alterations that occurred in the past 100 years and immune responses caused by H1N1 evolution. This work will facilitate development of future influenza therapeutics and prophylactics such as influenza vaccines.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Sym, D" uniqKey="Sym D">D. Sym</name></author><author><name sortKey="Patel, P N" uniqKey="Patel P">P. N. Patel</name></author><author><name sortKey="El Chaar, G M" uniqKey="El Chaar G">G. M. El Chaar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R. A. Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tong, S" uniqKey="Tong S">S. Tong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holmes, E C" uniqKey="Holmes E">E. C. Holmes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Girard, M P" uniqKey="Girard M">M. P. Girard</name></author><author><name sortKey="Tam, J S" uniqKey="Tam J">J. S. Tam</name></author><author><name sortKey="Assossou, O M" uniqKey="Assossou O">O. M. Assossou</name></author><author><name sortKey="Kieny, M P" uniqKey="Kieny M">M. P. Kieny</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Watanabe, T" uniqKey="Watanabe T">T. Watanabe</name></author><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y. Kawaoka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, D J" uniqKey="Smith D">D. J. Smith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nelson, M I" uniqKey="Nelson M">M. I. Nelson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Logan, W P" uniqKey="Logan W">W. P. Logan</name></author><author><name sortKey="Mackay, D G" uniqKey="Mackay D">D. G. MacKay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Collins, S D" uniqKey="Collins S">S. D. Collins</name></author><author><name sortKey="Lehmann, J" uniqKey="Lehmann J">J. Lehmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scholtissek, C" uniqKey="Scholtissek C">C. Scholtissek</name></author><author><name sortKey="Rohde, W" uniqKey="Rohde W">W. Rohde</name></author><author><name sortKey="Von, H V" uniqKey="Von H">H. V. Von</name></author><author><name sortKey="Rott, R" uniqKey="Rott R">R. Rott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Salk, J E" uniqKey="Salk J">J. E. Salk</name></author><author><name sortKey="Suriano, P C" uniqKey="Suriano P">P. C. Suriano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kilbourne, E D" uniqKey="Kilbourne E">E. D. Kilbourne</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Shinde, V" uniqKey="Shinde V">V. Shinde</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Manicassamy, B" uniqKey="Manicassamy B">B. Manicassamy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greenberg, M E" uniqKey="Greenberg M">M. E. Greenberg</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Fang, Y" uniqKey="Fang Y">Y. Fang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rowe, T" uniqKey="Rowe T">T. Rowe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, S S" uniqKey="Huang S">S. S. Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, S S" uniqKey="Huang S">S. S. Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kelvin, A A" uniqKey="Kelvin A">A. A. Kelvin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maines, T R" uniqKey="Maines T">T. R. Maines</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Banner, D" uniqKey="Banner D">D. Banner</name></author><author><name sortKey="Kelvin, A A" uniqKey="Kelvin A">A. A. Kelvin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cameron, M J" uniqKey="Cameron M">M. J. Cameron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leon, A J" uniqKey="Leon A">A. J. Leon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Danesh, A" uniqKey="Danesh A">A. Danesh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zitzow, L A" uniqKey="Zitzow L">L. A. Zitzow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rossman, J S" uniqKey="Rossman J">J. S. Rossman</name></author><author><name sortKey="Lamb, R A" uniqKey="Lamb R">R. A. Lamb</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dowdle, W R" uniqKey="Dowdle W">W. R. Dowdle</name></author><author><name sortKey="Coleman, M T" uniqKey="Coleman M">M. T. Coleman</name></author><author><name sortKey="Mostow, S R" uniqKey="Mostow S">S. R. Mostow</name></author><author><name sortKey="Kaye, H S" uniqKey="Kaye H">H. S. Kaye</name></author><author><name sortKey="Schoenbaum, S C" uniqKey="Schoenbaum S">S. C. Schoenbaum</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kilbourne, E D" uniqKey="Kilbourne E">E. D. Kilbourne</name></author><author><name sortKey="Christenson, W N" uniqKey="Christenson W">W. N. Christenson</name></author><author><name sortKey="Sande, M" uniqKey="Sande M">M. Sande</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Potter, C W" uniqKey="Potter C">C. W. Potter</name></author><author><name sortKey="Oxford, J S" uniqKey="Oxford J">J. S. Oxford</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name></author><author><name sortKey="Deng, Y M" uniqKey="Deng Y">Y. M. Deng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aguilar Yanez, J M" uniqKey="Aguilar Yanez J">J. M. Aguilar-Yanez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Glezen, W P" uniqKey="Glezen W">W. P. Glezen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klontz, K C" uniqKey="Klontz K">K. C. Klontz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shrestha, S S" uniqKey="Shrestha S">S. S. Shrestha</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Potter, C W" uniqKey="Potter C">C. W. Potter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kilbourne, E D" uniqKey="Kilbourne E">E. D. Kilbourne</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Robertson, J S" uniqKey="Robertson J">J. S. Robertson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hay, A J" uniqKey="Hay A">A. J. Hay</name></author><author><name sortKey="Gregory, V" uniqKey="Gregory V">V. Gregory</name></author><author><name sortKey="Douglas, A R" uniqKey="Douglas A">A. R. Douglas</name></author><author><name sortKey="Lin, Y P" uniqKey="Lin Y">Y. P. Lin</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Garten, R J" uniqKey="Garten R">R. J. Garten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Couch, R B" uniqKey="Couch R">R. B. Couch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hancock, K" uniqKey="Hancock K">K. Hancock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miller, E" uniqKey="Miller E">E. Miller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Itoh, Y" uniqKey="Itoh Y">Y. Itoh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carter, D M" uniqKey="Carter D">D. M. Carter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Donnell, C D" uniqKey="O Donnell C">C. D. O'Donnell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Teare, E L" uniqKey="Teare E">E. L. Teare</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Belser, J A" uniqKey="Belser J">J. A. Belser</name></author><author><name sortKey="Katz, J M" uniqKey="Katz J">J. M. Katz</name></author><author><name sortKey="Tumpey, T M" uniqKey="Tumpey T">T. M. Tumpey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Danesh, A" uniqKey="Danesh A">A. Danesh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pan, K" uniqKey="Pan K">K. Pan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reuman, P D" uniqKey="Reuman P">P. D. Reuman</name></author><author><name sortKey="Keely, S" uniqKey="Keely S">S. Keely</name></author><author><name sortKey="Schiff, G M" uniqKey="Schiff G">G. M. Schiff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tamura, K" uniqKey="Tamura K">K. Tamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tamura, K" uniqKey="Tamura K">K. Tamura</name></author><author><name sortKey="Nei, M" uniqKey="Nei M">M. Nei</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Larkin, M A" uniqKey="Larkin M">M. A. Larkin</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id><journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id><journal-title-group><journal-title>Scientific Reports</journal-title></journal-title-group><issn pub-type="epub">2045-2322</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23608887</article-id><article-id pub-id-type="pmc">3633051</article-id><article-id pub-id-type="pii">srep01698</article-id><article-id pub-id-type="doi">10.1038/srep01698</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Stephen S. H.</given-names></name><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a2">2</xref><xref ref-type="aff" rid="a8">8</xref></contrib><contrib contrib-type="author"><name><surname>Lin</surname><given-names>Zhen</given-names></name><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a5">5</xref><xref ref-type="aff" rid="a8">8</xref></contrib><contrib contrib-type="author"><name><surname>Banner</surname><given-names>David</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>León</surname><given-names>Alberto J.</given-names></name><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a5">5</xref></contrib><contrib contrib-type="author"><name><surname>Paquette</surname><given-names>Stéphane G.</given-names></name><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a6">6</xref></contrib><contrib contrib-type="author"><name><surname>Rubin</surname><given-names>Barry</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Rubino</surname><given-names>Salvatore</given-names></name><xref ref-type="aff" rid="a4">4</xref></contrib><contrib contrib-type="author"><name><surname>Guan</surname><given-names>Yi</given-names></name><xref ref-type="aff" rid="a5">5</xref></contrib><contrib contrib-type="author"><name><surname>Kelvin</surname><given-names>David J.</given-names></name><xref ref-type="corresp" rid="c1">a</xref><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a2">2</xref><xref ref-type="aff" rid="a4">4</xref><xref ref-type="aff" rid="a5">5</xref><xref ref-type="aff" rid="a6">6</xref></contrib><contrib contrib-type="author"><name><surname>Kelvin</surname><given-names>Alyson A.</given-names></name><xref ref-type="aff" rid="a7">7</xref></contrib><aff id="a1"><label>1</label><institution>Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</aff><aff id="a2"><label>2</label><institution>Department of Immunology, Faculty of Medicine, University of Toronto</institution>, Toronto, Ontario, Canada</aff><aff id="a3"><label>3</label><institution>Division of Vascular Surgery, Peter Munk Cardiac Centre, Toronto General Hospital Research Institute, University Health Network</institution>, Toronto, Ontario, Canada</aff><aff id="a4"><label>4</label><institution>Universita' degli Studi di Sassari, Sezione di Microbiologia Sperimentale e Clinica</institution>, Dipartimento di Scienze Biomediche, Viale San Pietro 43/b, 07100 Sassari, Italia</aff><aff id="a5"><label>5</label><institution>International Institute of Infection and Immunity, Shantou University Medical College</institution>, Shantou, Guangdong, China</aff><aff id="a6"><label>6</label><institution>Institute of Medical Science, Faculty of Medicine, University of Toronto</institution>, Toronto, Ontario, Canada</aff><aff id="a7"><label>7</label><institution>Immune Diagnostics & Research</institution>, Toronto, Ontario, Canada</aff><aff id="a8"><label>8</label>These authors contributed equally to this work.</aff></contrib-group><author-notes><corresp id="c1"><label>a</label><email>dkelvin@jidc.org</email></corresp></author-notes><pub-date pub-type="epub"><day>23</day><month>04</month><year>2013</year></pub-date><pub-date pub-type="collection"><year>2013</year></pub-date><volume>3</volume><elocation-id>1698</elocation-id><history><date date-type="received"><day>08</day><month>01</month><year>2013</year></date><date date-type="accepted"><day>05</day><month>04</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2013, Macmillan Publishers Limited. All rights reserved</copyright-statement><copyright-year>2013</copyright-year><copyright-holder>Macmillan Publishers Limited. All rights reserved</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-nd/3.0/">http://creativecommons.org/licenses/by-nc-nd/3.0/</ext-link></license-p></license></permissions><abstract><p>Evolution of H1N1 influenza A outbreaks of the past 100 years is interesting and significantly complex and details of H1N1 genetic drift remains unknown. Here we investigated the clinical characteristics and immune cross-reactivity of significant historical H1N1 strains. We infected ferrets with H1N1 strains from 1943, 1947, 1977, 1986, 1999, and 2009 and showed each produced a unique clinical signature. We found significant cross-reactivity between viruses with similar HA sequences. Interestingly, A/FortMonmouth/1/1947 antisera cross-reacted with A/USSR/90/1977 virus, thought to be a 1947 resurfaced virus. Importantly, our immunological data that didn't show cross-reactivity can be extrapolated to failure of past H1N1 influenza vaccines, ie. 1947, 1986 and 2009. Together, our results help to elucidate H1N1 immuno-genetic alterations that occurred in the past 100 years and immune responses caused by H1N1 evolution. This work will facilitate development of future influenza therapeutics and prophylactics such as influenza vaccines.</p></abstract></article-meta></front><floats-group><fig id="f1"><label>Figure 1</label><caption><title>History of H1N1 influenza epidemics and pandemics.</title></caption><graphic xlink:href="srep01698-f1"></graphic></fig><fig id="f2"><label>Figure 2</label><caption><title>Hemagglutination Inhibition (HI) analysis of H1N1 strain antisera shows cross-reactivity toward related strains.</title><p>Ferrets were infected with various H1N1 influenza strains Marton/43, FM/47, USSR/77, Taiwan/86, NCal/99, SI/06, Bris/07 and NY/09 and antisera was taken at 15 days pI. The antisera were used to measure HA specific antibody induction using hemagglutination inhibition assay against an H1N1 virus panel: PR/34, Marton/43, FM/47, USSR/77, Taiwan/86, NCal/99, SI/06, Bris/07 and NY/09 or Cal/09.</p></caption><graphic xlink:href="srep01698-f2"></graphic></fig><fig id="f3"><label>Figure 3</label><caption><title>Phylogenetic relationship and homology of the influenza A H1N1 HA gene.</title><p>Phylogenetic relationship and homology among the hemagglutinin protein from different influenza strains are depicted. Evolutionary relationships among historical influenza H1N1 strains were conducted in MEGA5 using the Maximum Likelihood method and 500 bootstrap replications (a). Antibody cross-reactivity (determined by HI) among influenza strains is indicated by using the same colors. The numerical values displayed next to the branches indicate the percentage of bootstrap replicates in which the associated sequences clustered together. Hemagglutinin protein sequence homology among several influenza strains (b). Influenza strains were grouped according to the HI cross-reactivity observed in the serum from previously-infected ferrets (groups A through F). Alignments of protein sequences were performed using the highly variable HA135-295 region, which belongs to the HA-RBD area.</p></caption><graphic xlink:href="srep01698-f3"></graphic></fig><table-wrap position="float" id="t1"><label>Table 1</label><caption><title>Temperature and Weight Summary of H1N1 virus infected ferrets. Clinical signs of infected ferrets were measured daily over 14 days. Temperature and weight were recorded daily until end day and are expressed as percentage relative to the pre-infection level at Day 0</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th align="center" valign="top" charoff="50">Marton/43</th><th align="center" valign="top" charoff="50">FM/47</th><th align="center" valign="top" charoff="50">USSR/77</th><th align="center" valign="top" charoff="50">Taiwan/86</th><th align="center" valign="top" charoff="50">NCal/99</th><th align="center" valign="top" charoff="50">NY/09</th></tr></thead><tbody valign="top"><tr><td align="justify" valign="top" charoff="50"><bold>Temperature</bold></td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="justify" valign="top" charoff="50">Peak Temp</td><td align="justify" valign="top" charoff="50">103%</td><td align="justify" valign="top" charoff="50">101.4%</td><td align="justify" valign="top" charoff="50">102%</td><td align="justify" valign="top" charoff="50">101.7%</td><td align="justify" valign="top" charoff="50">103.1%</td><td align="justify" valign="top" charoff="50">104%</td></tr><tr><td align="justify" valign="top" charoff="50">Day – Peak Temp</td><td align="justify" valign="top" charoff="50">Day 2</td><td align="justify" valign="top" charoff="50">Day 1</td><td align="justify" valign="top" charoff="50">Day 2</td><td align="justify" valign="top" charoff="50">Day 2</td><td align="justify" valign="top" charoff="50">Day 1</td><td align="justify" valign="top" charoff="50">Day 2</td></tr><tr><td align="justify" valign="top" charoff="50">Hypothermic Phase (y/n)</td><td align="justify" valign="top" charoff="50">No</td><td align="justify" valign="top" charoff="50">Below 100% but in normal range</td><td align="justify" valign="top" charoff="50">Below 100% but in normal range</td><td align="justify" valign="top" charoff="50">Slight Dip on Day 3</td><td align="justify" valign="top" charoff="50">Slight Dip on Day 12</td><td align="justify" valign="top" charoff="50">Yes</td></tr><tr><td align="justify" valign="top" charoff="50">Return to Baseline (y/n)</td><td align="justify" valign="top" charoff="50">No</td><td align="justify" valign="top" charoff="50">No</td><td align="justify" valign="top" charoff="50">Yes</td><td align="justify" valign="top" charoff="50">Yes</td><td align="justify" valign="top" charoff="50">No</td><td align="justify" valign="top" charoff="50">No</td></tr><tr><td align="justify" valign="top" charoff="50">Day 14 Temperature</td><td align="justify" valign="top" charoff="50">101.3%</td><td align="justify" valign="top" charoff="50">99%</td><td align="justify" valign="top" charoff="50">100%</td><td align="justify" valign="top" charoff="50">100.5%</td><td align="justify" valign="top" charoff="50">101%</td><td align="justify" valign="top" charoff="50">98%</td></tr><tr><td align="justify" valign="top" charoff="50"><bold>Weight</bold></td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="justify" valign="top" charoff="50">Lowest Weight</td><td align="justify" valign="top" charoff="50">98%</td><td align="justify" valign="top" charoff="50">No weight loss</td><td align="justify" valign="top" charoff="50">92%</td><td align="justify" valign="top" charoff="50">98%</td><td align="justify" valign="top" charoff="50">95%</td><td align="justify" valign="top" charoff="50">91%</td></tr><tr><td align="justify" valign="top" charoff="50">Day – Lowest Weights</td><td align="justify" valign="top" charoff="50">Day 2</td><td align="justify" valign="top" charoff="50">—</td><td align="justify" valign="top" charoff="50">Day 2</td><td align="justify" valign="top" charoff="50">Day 2</td><td align="justify" valign="top" charoff="50">Day 2</td><td align="justify" valign="top" charoff="50">Day 6 and Day 7</td></tr><tr><td align="justify" valign="top" charoff="50">Return to Baseline (y/n)</td><td align="justify" valign="top" charoff="50">Yes</td><td align="justify" valign="top" charoff="50">—</td><td align="justify" valign="top" charoff="50">Yes</td><td align="justify" valign="top" charoff="50">Yes</td><td align="justify" valign="top" charoff="50">Yes</td><td align="justify" valign="top" charoff="50">No</td></tr><tr><td align="justify" valign="top" charoff="50">Day Return to Baseline</td><td align="justify" valign="top" charoff="50">Day 3</td><td align="justify" valign="top" charoff="50">—</td><td align="justify" valign="top" charoff="50">Day 4</td><td align="justify" valign="top" charoff="50">Day 3</td><td align="justify" valign="top" charoff="50">Day 5</td><td align="justify" valign="top" charoff="50">—</td></tr></tbody></table></table-wrap></floats-group></pmc><affiliations><list><country><li>Canada</li><li>Italie</li><li>République populaire de Chine</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Huang, Stephen S H" sort="Huang, Stephen S H" uniqKey="Huang S" first="Stephen S. H." last="Huang">Stephen S. H. Huang</name></noRegion><name sortKey="Banner, David" sort="Banner, David" uniqKey="Banner D" first="David" last="Banner">David Banner</name><name sortKey="Huang, Stephen S H" sort="Huang, Stephen S H" uniqKey="Huang S" first="Stephen S. H." last="Huang">Stephen S. H. Huang</name><name sortKey="Kelvin, Alyson A" sort="Kelvin, Alyson A" uniqKey="Kelvin A" first="Alyson A." last="Kelvin">Alyson A. Kelvin</name><name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name><name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name><name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name><name sortKey="Le N, Alberto J" sort="Le N, Alberto J" uniqKey="Le N A" first="Alberto J." last="Le N">Alberto J. Le N</name><name sortKey="Lin, Zhen" sort="Lin, Zhen" uniqKey="Lin Z" first="Zhen" last="Lin">Zhen Lin</name><name sortKey="Paquette, Stephane G" sort="Paquette, Stephane G" uniqKey="Paquette S" first="Stéphane G." last="Paquette">Stéphane G. Paquette</name><name sortKey="Paquette, Stephane G" sort="Paquette, Stephane G" uniqKey="Paquette S" first="Stéphane G." last="Paquette">Stéphane G. Paquette</name><name sortKey="Rubin, Barry" sort="Rubin, Barry" uniqKey="Rubin B" first="Barry" last="Rubin">Barry Rubin</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Lin, Zhen" sort="Lin, Zhen" uniqKey="Lin Z" first="Zhen" last="Lin">Zhen Lin</name></noRegion><name sortKey="Guan, Yi" sort="Guan, Yi" uniqKey="Guan Y" first="Yi" last="Guan">Yi Guan</name><name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name><name sortKey="Le N, Alberto J" sort="Le N, Alberto J" uniqKey="Le N A" first="Alberto J." last="Le N">Alberto J. Le N</name></country><country name="Italie"><noRegion><name sortKey="Rubino, Salvatore" sort="Rubino, Salvatore" uniqKey="Rubino S" first="Salvatore" last="Rubino">Salvatore Rubino</name></noRegion><name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/H2N2V1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000897 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 000897 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= H2N2V1
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= PMC:3633051
|texte= Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:23608887" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a H2N2V1
| This area was generated with Dilib version V0.6.33. |  |