A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus
Identifieur interne : 000093 ( Pmc/Curation ); précédent : 000092; suivant : 000094A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus
Auteurs : Ying Wu [République populaire de Chine] ; Myungsam Cho [Corée du Sud] ; David Shore [États-Unis] ; Manki Song [Corée du Sud] ; Jungah Choi [Corée du Sud] ; Tao Jiang [République populaire de Chine] ; Yong-Qiang Deng [République populaire de Chine] ; Melissa Bourgeois [États-Unis] ; Lynn Almli [États-Unis] ; Hua Yang [États-Unis] ; Li-Mei Chen [États-Unis] ; Yi Shi [République populaire de Chine] ; Jianxu Qi [République populaire de Chine] ; An Li [République populaire de Chine] ; Kye Sook Yi [Corée du Sud] ; Minseok Chang [Corée du Sud] ; Jin Soo Bae [Corée du Sud] ; Hyunjoo Lee [Corée du Sud] ; Jiyoung Shin [Corée du Sud] ; James Stevens [États-Unis] ; Seoungsuh Hong [Corée du Sud] ; Cheng-Feng Qin [République populaire de Chine] ; George F. Gao [République populaire de Chine] ; Shin Jae Chang [Corée du Sud] ; Ruben O. Donis [États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2015.
Abstract
Effective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines.
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DOI: 10.1038/ncomms8708
PubMed: 26196962
PubMed Central: 4518248
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Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cho, Myungsam" sort="Cho, Myungsam" uniqKey="Cho M" first="Myungsam" last="Cho">Myungsam Cho</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shore, David" sort="Shore, David" uniqKey="Shore D" first="David" last="Shore">David Shore</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Influenza Division, Centers for Disease Control and Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Song, Manki" sort="Song, Manki" uniqKey="Song M" first="Manki" last="Song">Manki Song</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>International Vaccine Institute</institution>, Seoul 151-919,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Choi, Jungah" sort="Choi, Jungah" uniqKey="Choi J" first="Jungah" last="Choi">Jungah Choi</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>International Vaccine Institute</institution>, Seoul 151-919,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Tao" sort="Jiang, Tao" uniqKey="Jiang T" first="Tao" last="Jiang">Tao Jiang</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology</institution>, Beijing 100071,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Deng, Yong Qiang" sort="Deng, Yong Qiang" uniqKey="Deng Y" first="Yong-Qiang" last="Deng">Yong-Qiang Deng</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology</institution>, Beijing 100071,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bourgeois, Melissa" sort="Bourgeois, Melissa" uniqKey="Bourgeois M" first="Melissa" last="Bourgeois">Melissa 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Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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 wicri:level="1"><nlm:aff id="a4"><institution>Influenza Division, Centers for Disease Control and Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Yi" sort="Shi, Yi" uniqKey="Shi Y" first="Yi" last="Shi">Yi Shi</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Center for Influenza Research and Early-warning, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Qi, Jianxu" sort="Qi, Jianxu" uniqKey="Qi J" first="Jianxu" last="Qi">Jianxu Qi</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Center for Influenza Research and Early-warning, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, An" sort="Li, An" uniqKey="Li A" first="An" last="Li">An Li</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a8"><institution>College of Veterinary Medicine, Guangxi University</institution>, Nanning 530004,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yi, Kye Sook" sort="Yi, Kye Sook" uniqKey="Yi K" first="Kye Sook" last="Yi">Kye Sook Yi</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chang, Minseok" sort="Chang, Minseok" uniqKey="Chang M" first="Minseok" last="Chang">Minseok Chang</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bae, Jin Soo" sort="Bae, Jin Soo" uniqKey="Bae J" first="Jin Soo" last="Bae">Jin Soo Bae</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lee, Hyunjoo" sort="Lee, Hyunjoo" uniqKey="Lee H" first="Hyunjoo" last="Lee">Hyunjoo Lee</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shin, Jiyoung" sort="Shin, Jiyoung" uniqKey="Shin J" first="Jiyoung" last="Shin">Jiyoung Shin</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Stevens, James" sort="Stevens, James" uniqKey="Stevens J" first="James" last="Stevens">James Stevens</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Influenza Division, Centers for Disease Control and Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hong, Seoungsuh" sort="Hong, Seoungsuh" uniqKey="Hong S" first="Seoungsuh" last="Hong">Seoungsuh Hong</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Qin, Cheng Feng" sort="Qin, Cheng Feng" uniqKey="Qin C" first="Cheng-Feng" last="Qin">Cheng-Feng Qin</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology</institution>, Beijing 100071,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Center for Influenza Research and Early-warning, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a9"><institution>Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC)</institution>, Beijing 102206,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chang, Shin Jae" sort="Chang, Shin Jae" uniqKey="Chang S" first="Shin Jae" last="Chang">Shin Jae Chang</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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 wicri:level="1"><nlm:aff id="a4"><institution>Influenza Division, Centers for Disease Control and Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26196962</idno><idno type="pmc">4518248</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518248</idno><idno type="RBID">PMC:4518248</idno><idno type="doi">10.1038/ncomms8708</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000093</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000093</idno><idno type="wicri:Area/Pmc/Curation">000093</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000093</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus</title><author><name sortKey="Wu, Ying" sort="Wu, Ying" uniqKey="Wu Y" first="Ying" last="Wu">Ying Wu</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Center for Influenza Research and Early-warning, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cho, Myungsam" sort="Cho, Myungsam" uniqKey="Cho M" first="Myungsam" last="Cho">Myungsam Cho</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shore, David" sort="Shore, David" uniqKey="Shore D" first="David" last="Shore">David Shore</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Influenza Division, Centers for Disease Control and Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Song, Manki" sort="Song, Manki" uniqKey="Song M" first="Manki" last="Song">Manki Song</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>International Vaccine Institute</institution>, Seoul 151-919,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Choi, Jungah" sort="Choi, Jungah" uniqKey="Choi J" first="Jungah" last="Choi">Jungah Choi</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>International Vaccine Institute</institution>, Seoul 151-919,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Tao" sort="Jiang, Tao" uniqKey="Jiang T" first="Tao" last="Jiang">Tao Jiang</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology</institution>, Beijing 100071,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Deng, Yong Qiang" sort="Deng, Yong Qiang" uniqKey="Deng Y" first="Yong-Qiang" last="Deng">Yong-Qiang Deng</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology</institution>, Beijing 100071,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bourgeois, Melissa" sort="Bourgeois, Melissa" uniqKey="Bourgeois M" first="Melissa" last="Bourgeois">Melissa Bourgeois</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Influenza Division, Centers for Disease Control and Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Almli, Lynn" sort="Almli, Lynn" uniqKey="Almli L" first="Lynn" last="Almli">Lynn Almli</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Influenza Division, Centers for Disease Control and Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Hua" sort="Yang, Hua" uniqKey="Yang H" first="Hua" last="Yang">Hua Yang</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Influenza Division, Centers for Disease Control and Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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 wicri:level="1"><nlm:aff id="a4"><institution>Influenza Division, Centers for Disease Control and Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Yi" sort="Shi, Yi" uniqKey="Shi Y" first="Yi" last="Shi">Yi Shi</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Center for Influenza Research and Early-warning, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Qi, Jianxu" sort="Qi, Jianxu" uniqKey="Qi J" first="Jianxu" last="Qi">Jianxu Qi</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Center for Influenza Research and Early-warning, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, An" sort="Li, An" uniqKey="Li A" first="An" last="Li">An Li</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a8"><institution>College of Veterinary Medicine, Guangxi University</institution>, Nanning 530004,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yi, Kye Sook" sort="Yi, Kye Sook" uniqKey="Yi K" first="Kye Sook" last="Yi">Kye Sook Yi</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chang, Minseok" sort="Chang, Minseok" uniqKey="Chang M" first="Minseok" last="Chang">Minseok Chang</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bae, Jin Soo" sort="Bae, Jin Soo" uniqKey="Bae J" first="Jin Soo" last="Bae">Jin Soo Bae</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lee, Hyunjoo" sort="Lee, Hyunjoo" uniqKey="Lee H" first="Hyunjoo" last="Lee">Hyunjoo Lee</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shin, Jiyoung" sort="Shin, Jiyoung" uniqKey="Shin J" first="Jiyoung" last="Shin">Jiyoung Shin</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Stevens, James" sort="Stevens, James" uniqKey="Stevens J" first="James" last="Stevens">James Stevens</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Influenza Division, Centers for Disease Control and Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hong, Seoungsuh" sort="Hong, Seoungsuh" uniqKey="Hong S" first="Seoungsuh" last="Hong">Seoungsuh Hong</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Qin, Cheng Feng" sort="Qin, Cheng Feng" uniqKey="Qin C" first="Cheng-Feng" last="Qin">Cheng-Feng Qin</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology</institution>, Beijing 100071,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Center for Influenza Research and Early-warning, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a9"><institution>Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC)</institution>, Beijing 102206,<country>China</country>.</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chang, Shin Jae" sort="Chang, Shin Jae" uniqKey="Chang S" first="Shin Jae" last="Chang">Shin Jae Chang</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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 wicri:level="1"><nlm:aff id="a4"><institution>Influenza Division, Centers for Disease Control and Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Effective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Liu, J" uniqKey="Liu J">J. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Nat Commun</journal-id><journal-id journal-id-type="iso-abbrev">Nat Commun</journal-id><journal-title-group><journal-title>Nature Communications</journal-title></journal-title-group><issn pub-type="epub">2041-1723</issn><publisher><publisher-name>Nature Pub. Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26196962</article-id><article-id pub-id-type="pmc">4518248</article-id><article-id pub-id-type="pii">ncomms8708</article-id><article-id pub-id-type="doi">10.1038/ncomms8708</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Wu</surname><given-names>Ying</given-names></name><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a2">2</xref><xref ref-type="author-notes" rid="n1">*</xref></contrib><contrib contrib-type="author"><name><surname>Cho</surname><given-names>MyungSam</given-names></name><xref ref-type="aff" rid="a3">3</xref><xref ref-type="author-notes" rid="n1">*</xref></contrib><contrib contrib-type="author"><name><surname>Shore</surname><given-names>David</given-names></name><xref ref-type="aff" rid="a4">4</xref><xref ref-type="author-notes" rid="n1">*</xref></contrib><contrib contrib-type="author"><name><surname>Song</surname><given-names>Manki</given-names></name><xref ref-type="aff" rid="a5">5</xref></contrib><contrib contrib-type="author"><name><surname>Choi</surname><given-names>JungAh</given-names></name><xref ref-type="aff" rid="a5">5</xref></contrib><contrib contrib-type="author"><name><surname>Jiang</surname><given-names>Tao</given-names></name><xref ref-type="aff" rid="a6">6</xref></contrib><contrib contrib-type="author"><name><surname>Deng</surname><given-names>Yong-Qiang</given-names></name><xref ref-type="aff" rid="a6">6</xref></contrib><contrib contrib-type="author"><name><surname>Bourgeois</surname><given-names>Melissa</given-names></name><xref ref-type="aff" rid="a4">4</xref></contrib><contrib contrib-type="author"><name><surname>Almli</surname><given-names>Lynn</given-names></name><xref ref-type="aff" rid="a4">4</xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Hua</given-names></name><xref ref-type="aff" rid="a4">4</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Li-Mei</given-names></name><xref ref-type="aff" rid="a4">4</xref></contrib><contrib contrib-type="author"><name><surname>Shi</surname><given-names>Yi</given-names></name><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a2">2</xref><xref ref-type="aff" rid="a7">7</xref></contrib><contrib contrib-type="author"><name><surname>Qi</surname><given-names>Jianxu</given-names></name><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a2">2</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>An</given-names></name><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a8">8</xref></contrib><contrib contrib-type="author"><name><surname>Yi</surname><given-names>Kye Sook</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Chang</surname><given-names>MinSeok</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Bae</surname><given-names>Jin Soo</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>HyunJoo</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Shin</surname><given-names>JiYoung</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Stevens</surname><given-names>James</given-names></name><xref ref-type="aff" rid="a4">4</xref></contrib><contrib contrib-type="author"><name><surname>Hong</surname><given-names>SeoungSuh</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Qin</surname><given-names>Cheng-Feng</given-names></name><xref ref-type="corresp" rid="c1">a</xref><xref ref-type="aff" rid="a6">6</xref><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-0632-2807</contrib-id></contrib><contrib contrib-type="author"><name><surname>Gao</surname><given-names>George F.</given-names></name><xref ref-type="corresp" rid="c2">b</xref><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a2">2</xref><xref ref-type="aff" rid="a7">7</xref><xref ref-type="aff" rid="a9">9</xref></contrib><contrib contrib-type="author"><name><surname>Chang</surname><given-names>Shin Jae</given-names></name><xref ref-type="corresp" rid="c3">c</xref><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Donis</surname><given-names>Ruben O.</given-names></name><xref ref-type="corresp" rid="c4">d</xref><xref ref-type="aff" rid="a4">4</xref></contrib><aff id="a1"><label>1</label><institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</aff><aff id="a2"><label>2</label><institution>Center for Influenza Research and Early-warning, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</aff><aff id="a3"><label>3</label><institution>Biotechnology Research Institute, Celltrion, Inc.</institution>, Incheon 406-840,<country>South Korea</country>.</aff><aff id="a4"><label>4</label><institution>Influenza Division, Centers for Disease Control and Prevention</institution>, Atlanta, Georgia 30333,<country>USA</country>.</aff><aff id="a5"><label>5</label><institution>International Vaccine Institute</institution>, Seoul 151-919,<country>South Korea</country>.</aff><aff id="a6"><label>6</label><institution>Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology</institution>, Beijing 100071,<country>China</country>.</aff><aff id="a7"><label>7</label><institution>Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences</institution>, No. 1 West Beichen Road, Beijing 100101,<country>China</country>.</aff><aff id="a8"><label>8</label><institution>College of Veterinary Medicine, Guangxi University</institution>, Nanning 530004,<country>China</country>.</aff><aff id="a9"><label>9</label><institution>Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC)</institution>, Beijing 102206,<country>China</country>.</aff></contrib-group><author-notes><corresp id="c1"><label>a</label><email>qincf@bmi.ac.cn</email></corresp><corresp id="c2"><label>b</label><email>gaof@im.ac.cn</email></corresp><corresp id="c3"><label>c</label><email>ShinJae.Chang@celltrion.com</email></corresp><corresp id="c4"><label>d</label><email>rvd6@cdc.gov</email></corresp><fn id="n1"><label>*</label><p>These authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="epub"><day>21</day><month>07</month><year>2015</year></pub-date><pub-date pub-type="collection"><year>2015</year></pub-date><volume>6</volume><elocation-id>7708</elocation-id><history><date date-type="received"><day>26</day><month>01</month><year>2015</year></date><date date-type="accepted"><day>03</day><month>06</month><year>2015</year></date></history><permissions><copyright-statement>Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</copyright-statement><copyright-year>2015</copyright-year><copyright-holder>Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link></license-p></license></permissions><abstract><p>Effective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines.</p></abstract><abstract abstract-type="web-summary"><p><inline-graphic id="i1" xlink:href="ncomms8708-i1.jpg"></inline-graphic>Monoclonal antibodies with broadly neutralizing activity are being developed as potential treatment of influenza infections. Here, the authors describe a broadly neutralizing antibody with an unusual mode of binding to viral haemagglutinin, which has been isolated from patients convalescent from pandemic H1N1 influenza infection.</p></abstract></article-meta></front><floats-group><fig id="f1"><label>Figure 1</label><caption><title>Neutralization activity of human mAbs against different influenza A viruses.</title><p>Initial MN assay results against various influenza subtypes with selected mAbs. The initial concentration was 10 μg ml<sup>−1</sup>,and therefore the bars truncated at 10 μg ml<sup>−1</sup> upper limit denote a neutralization end point >10 μg ml<sup>−1</sup>. The experiments have been performed by three times.</p></caption><graphic xlink:href="ncomms8708-f1"></graphic></fig><fig id="f2"><label>Figure 2</label><caption><title>Structures of CT149/H7 and CT149/H3 complexes.</title><p>The overall structures of CT149/H7 (<bold>a</bold>) and CT149/H3 (<bold>d</bold>) complexes are displayed in a cartoon representation. The antibody CT149 binds the stem regions of both H7 and H3 HA. The epitope residues in H7 (<bold>b</bold>) and H3 (<bold>e</bold>) are denoted in black characters. The purple text refers to the epitope residues in the neighbouring protomer. Residues contacted by the CT149 heavy chain are coloured magenta in both surface representations, whereas residues contacted by the CT149 light chain are coloured yellow The residues of CT149 responsible for the HA binding in the CT149/H7 complex (<bold>c</bold>) and in the CT149/H3 complex (<bold>f</bold>) are marked in black characters. The heavy chain is coloured in magenta and the light chain is coloured in yellow. The residues contacting the HA are coloured in pink for the heavy chain and coloured in orange for the light chain.</p></caption><graphic xlink:href="ncomms8708-f2"></graphic></fig><fig id="f3"><label>Figure 3</label><caption><title>CT149 interactions with H3/H7 and comparison with other stem-bound antibodies.</title><p>(<bold>a</bold>–<bold>h</bold>)The epitope residues on the HA are displayed in a surface representation. The epitope residues in HA1 are coloured in green and those in HA2 are coloured in cyan. The interacting CDR loops of CT149 are displayed in a cartoon representation. The CDR loops of the light chain are coloured in yellow and those of the heavy chain are coloured in magenta.</p></caption><graphic xlink:href="ncomms8708-f3"></graphic></fig><fig id="f4"><label>Figure 4</label><caption><title>Structural basis for CT149 as a group 2 preferential neutralizing antibody.</title><p>The light chain of CT149 contacts the region around the extended loop between helixes A and B of HA, and the heavy chain of CT149 contacts the fusion subdomain of HA. By superimposition of H1 and H7 HAs, we have generated a H1/CT149 complex model. There is a relatively conserved glycosylation site in the region around the extended loop of group 1 HA, which could hinder binding of the CT149 light chain.</p></caption><graphic xlink:href="ncomms8708-f4"></graphic></fig><fig id="f5"><label>Figure 5</label><caption><title>Protection efficacy of CT149 in mice.</title><p>Mice were infected with a lethal dose of mouse-adapted A/California/04/2009 (H1N1) (<italic>n</italic>=10 per group) (<bold>a</bold>), A/Vietnam /1203/2004 (H5N1) (<italic>n</italic>=10 per group) (<bold>b</bold>), mouse-adapted A/Hongkong/1/1968 (H3N2) (<bold>c</bold>) or A/Anhui/1/2013 (H7N9) (<italic>n</italic>=10 per group) (<bold>d</bold>). The mice were then treated with CT149, isotype-matched negative control antibody (CT-P6) or PBS 24 h before or 24 or 48 h after infection, and surrogate survival end points and body weight changes were monitored for 14 days. Left panels are Kaplan–Meier survival probability curves and right panels represent mean change in body weight per group expressed as the percentage of baseline body weight.</p></caption><graphic xlink:href="ncomms8708-f5"></graphic></fig><table-wrap position="float" id="t1"><label>Table 1</label><caption><title>Neutralization activity of CT149 against viruses from diverse HA subtypes and antigenic drift variants.</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="left"></col><col align="char" char="."></col></colgroup><thead valign="bottom"><tr><th align="center" valign="top" charoff="50">Group</th><th align="center" valign="top" charoff="50">Subtype</th><th align="left" valign="top" charoff="50">Virus</th><th align="center" valign="top" char="." charoff="50">MN endpoint (μg ml<sup>−1</sup>)</th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">1</td><td align="center" valign="top" charoff="50">H1N1</td><td align="left" valign="top" charoff="50">A/Ohio/83</td><td align="center" valign="top" char="." charoff="50">>10</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Solomon Islands/2006</td><td align="center" valign="top" char="." charoff="50">>10</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Ohio/07/2009</td><td align="center" valign="top" char="." charoff="50">5</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Texas/05/2009-RG15</td><td align="center" valign="top" char="." charoff="50">>10</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Texas/18/2009-RG18</td><td align="center" valign="top" char="." charoff="50">>10</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/California/04/2009</td><td align="center" valign="top" char="." charoff="50">>10</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">H2N2</td><td align="left" valign="top" charoff="50">A/Ann Arbor/6/60 ca</td><td align="center" valign="top" char="." charoff="50">>10</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">H5N1</td><td align="left" valign="top" charoff="50">A/Vietnam/1203/04 (VNH5N1-PR8/CDC-RG)</td><td align="char" valign="top" char="." charoff="50">2.5</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Anhui/01/2005(H5N1)-PR8-IBCDC-RG6</td><td align="char" valign="top" char="." charoff="50">0.625</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">H9N2</td><td align="left" valign="top" charoff="50">A/ck/HK/G9/97(H9N2)/PR8-IBCDC-2</td><td align="char" valign="top" char="." charoff="50">0.312</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Green-winged teal/209/TX/2009</td><td align="char" valign="top" char="." charoff="50">0.156</td></tr><tr><td align="left" valign="top" charoff="50">2</td><td align="center" valign="top" charoff="50">H3N2</td><td align="left" valign="top" charoff="50">A/Hong Kong/68</td><td align="char" valign="top" char="." charoff="50">2.5</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Philippines/2/1982</td><td align="char" valign="top" char="." charoff="50">0.625</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Beijing/353/89-X109-H3N2 PR8 reassortant</td><td align="char" valign="top" char="." charoff="50">0.156</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Beijing/32/92-R-H3N2 PR8 reassortant</td><td align="char" valign="top" char="." charoff="50">0.078</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Johannesburg/33/94 R-H3N2 PR8 reassortant</td><td align="char" valign="top" char="." charoff="50">0.625</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Nanchang/933/95</td><td align="char" valign="top" char="." charoff="50">0.625</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Sydney/5/97</td><td align="char" valign="top" char="." charoff="50">0.625</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Panama/2007/99</td><td align="char" valign="top" char="." charoff="50">0.312</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Wyoming/3/03.rg</td><td align="center" valign="top" char="." charoff="50">5</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Brisbane/10/07</td><td align="char" valign="top" char="." charoff="50">0.625</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">H7N2</td><td align="left" valign="top" charoff="50">A/turkey/Virginia/2002(H7N2)/PR8-IBCDC-5</td><td align="center" valign="top" char="." charoff="50">10</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">H7N9</td><td align="left" valign="top" charoff="50">A/Anhui/1/2013</td><td align="char" valign="top" char="." charoff="50">0.904</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Shanghai/2/2013</td><td align="char" valign="top" char="." charoff="50">1.17</td></tr></tbody></table><table-wrap-foot><fn id="t1-fn1"><p>HA, hemagglutinin; MN, microneutralization; RG, reverse genetics.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t2"><label>Table 2</label><caption><title>SPR analysis of CT149 with recombinant HAs.</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="left"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50">Subtype</th><th align="left" valign="top" charoff="50">HA donor virus</th><th align="center" valign="top" charoff="50"><italic>K</italic><sub>d</sub>, M</th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">H1N1</td><td align="left" valign="top" charoff="50">A/California/04/2009<xref ref-type="fn" rid="t2-fn2">*</xref></td><td align="center" valign="top" charoff="50">3.06E-08</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Texas/05/2009<xref ref-type="fn" rid="t2-fn2">*</xref></td><td align="center" valign="top" charoff="50">3.38E-08</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Solomon Island/03/2006<xref ref-type="fn" rid="t2-fn3">†</xref></td><td align="center" valign="top" charoff="50">3.45E-07</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Ohio/07/2009<xref ref-type="fn" rid="t2-fn3">†</xref></td><td align="center" valign="top" charoff="50">5.13E-08</td></tr><tr><td align="left" valign="top" charoff="50">H3N2</td><td align="left" valign="top" charoff="50">A/Philippines/2/1982<xref ref-type="fn" rid="t2-fn2">*</xref></td><td align="center" valign="top" charoff="50">4.56E-11</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">A/Brisbane/10/2007<xref ref-type="fn" rid="t2-fn4">‡</xref></td><td align="center" valign="top" charoff="50">1.81E-09</td></tr><tr><td align="left" valign="top" charoff="50">H5N1</td><td align="left" valign="top" charoff="50">A/Vietnam/1203/2004<xref ref-type="fn" rid="t2-fn2">*</xref></td><td align="center" valign="top" charoff="50">2.94E-09</td></tr><tr><td align="left" valign="top" charoff="50">H7N9</td><td align="left" valign="top" charoff="50">A/Anhui/1/2013</td><td align="center" valign="top" charoff="50">1.83E-10</td></tr></tbody></table><table-wrap-foot><fn id="t2-fn1"><p>HA, hemagglutinin; SPR, surface plasmon resonance.</p></fn><fn id="t2-fn2"><p><sup>*</sup>Immune Technology</p></fn><fn id="t2-fn3"><p><sup>†</sup>Sino Biological</p></fn><fn id="t2-fn4"><p><sup>‡</sup>IRR</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t3"><label>Table 3</label><caption><title>Data collection and refinement statistics (molecular replacement).</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></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">CT149/H7</th><th align="center" valign="top" charoff="50">CT149/H3</th></tr></thead><tbody valign="top"><tr><td colspan="3" align="left" valign="top" charoff="50"><italic>Data collection</italic></td></tr><tr><td align="left" valign="top" charoff="50"> Space group</td><td align="center" valign="top" charoff="50">R3<sub>2</sub></td><td align="center" valign="top" charoff="50">P3<sub>1</sub></td></tr><tr><td align="left" valign="top" charoff="50"> Cell dimensions</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> <italic>a</italic>, <italic>b</italic>, <italic>c</italic> (Å)</td><td align="center" valign="top" charoff="50">126.9, 126.9, 409.6</td><td align="center" valign="top" charoff="50">128.7, 128.7, 428.3</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>α</italic>, <italic>β</italic>, <italic>γ</italic>(°)</td><td align="center" valign="top" charoff="50">90.00, 90.00, 120.00</td><td align="center" valign="top" charoff="50">90.00, 90.00, 120.00</td></tr><tr><td align="left" valign="top" charoff="50"> Resolution (Å)</td><td align="center" valign="top" charoff="50">50.0–2.8 (2.90–2.80)*</td><td align="center" valign="top" charoff="50">50–3.5 (3.63–3.50)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>R</italic><sub>sym</sub> or <italic>R</italic><sub>merge</sub></td><td align="center" valign="top" charoff="50">11.5 (88.3)</td><td align="center" valign="top" charoff="50">13.6 (71.8)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>I</italic>/σ<italic>I</italic></td><td align="center" valign="top" charoff="50">17.2 (2.4)</td><td align="center" valign="top" charoff="50">11.9 (1.7)</td></tr><tr><td align="left" valign="top" charoff="50"> Completeness (%)</td><td align="center" valign="top" charoff="50">99.5 (99.9)</td><td align="center" valign="top" charoff="50">99.5 (100)</td></tr><tr><td align="left" valign="top" charoff="50"> Redundancy</td><td align="center" valign="top" charoff="50">7.8 (7.7)</td><td align="center" valign="top" charoff="50">3.7 (3.9)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td> </td><td> </td></tr><tr><td colspan="3" align="left" valign="top" charoff="50"><italic>Refinement</italic></td></tr><tr><td align="left" valign="top" charoff="50"> Resolution (Å)</td><td align="center" valign="top" charoff="50">48.4–2.8 (2.90–2.80)</td><td align="center" valign="top" charoff="50">48.3–3.5 (3.50–3.59)</td></tr><tr><td align="left" valign="top" charoff="50"> No. of reflections</td><td align="center" valign="top" charoff="50">31,755</td><td align="center" valign="top" charoff="50">94,551</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>R</italic><sub>work</sub>/<italic>R</italic><sub>free</sub></td><td align="center" valign="top" charoff="50">26.4/31.1</td><td align="center" valign="top" charoff="50">23.9/27.8</td></tr><tr><td align="left" valign="top" charoff="50"> No. of atoms</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Protein</td><td align="center" valign="top" charoff="50">5,650</td><td align="center" valign="top" charoff="50">42,616</td></tr><tr><td align="left" valign="top" charoff="50"> Ligand/ion</td><td align="center" valign="top" charoff="50">0</td><td align="center" valign="top" charoff="50">636</td></tr><tr><td align="left" valign="top" charoff="50"> Water</td><td align="center" valign="top" charoff="50">25</td><td align="center" valign="top" charoff="50">0</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>B</italic>-factors</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Protein</td><td align="center" valign="top" charoff="50">75.313</td><td align="center" valign="top" charoff="50">120.4</td></tr><tr><td align="left" valign="top" charoff="50"> Ligand/ion</td><td align="center" valign="top" charoff="50">0</td><td align="center" valign="top" charoff="50">138.4</td></tr><tr><td align="left" valign="top" charoff="50"> Water</td><td align="center" valign="top" charoff="50">58.399</td><td align="center" valign="top" charoff="50">0</td></tr><tr><td align="left" valign="top" charoff="50"> R.m.s.d.</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Bond lengths (Å)</td><td align="center" valign="top" charoff="50">0.004</td><td align="center" valign="top" charoff="50">0.019</td></tr><tr><td align="left" valign="top" charoff="50"> Bond angles (°)</td><td align="center" valign="top" charoff="50">0.780</td><td align="center" valign="top" charoff="50">1.58</td></tr></tbody></table><table-wrap-foot><fn 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