Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine
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Corti, Davide
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Suguitan Jr., Amorsolo
Laboratory of Infectious Diseases, NIAID, NIH, Rockville, Maryland, USA
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Pinna, Debora
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Silacci, Chiara
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Fernandez-Rodriguez, Blanca M.
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Vanzetta, Fabrizia
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Santos, Celia
Laboratory of Infectious Diseases, NIAID, NIH, Rockville, Maryland, USA
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Luke, Catherine J.
Laboratory of Infectious Diseases, NIAID, NIH, Rockville, Maryland, USA
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Torres-Velez, Fernando J.
Comparative Medicine Branch, NIAID, NIH, Rockville, Maryland, USA
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Temperton, Nigel J.
MRC/UCL Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom
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Weiss, Robin A.
MRC/UCL Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom
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Sallusto, Federica
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Subbarao, Kanta
Laboratory of Infectious Diseases, NIAID, NIH, Rockville, Maryland, USA
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Lanzavecchia, Antonio
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Published in:
- The Journal of clinical investigation. - 2010, vol. 120, no. 5, p. 1663-1673
English
The target of neutralizing antibodies that protect against influenza virus infection is the viral protein HA. Genetic and antigenic variation in HA has been used to classify influenza viruses into subtypes (H1–H16). The neutralizing antibody response to influenza virus is thought to be specific for a few antigenically related isolates within a given subtype. However, while heterosubtypic antibodies capable of neutralizing multiple influenza virus subtypes have been recently isolated from phage display libraries, it is not known whether such antibodies are produced in the course of an immune response to influenza virus infection or vaccine. Here we report that, following vaccination with seasonal influenza vaccine containing H1 and H3 influenza virus subtypes, some individuals produce antibodies that cross-react with H5 HA. By immortalizing IgG-expressing B cells from 4 individuals, we isolated 20 heterosubtypic mAbs that bound and neutralized viruses belonging to several HA subtypes (H1, H2, H5, H6, and H9), including the pandemic A/California/07/09 H1N1 isolate. The mAbs used different VH genes and carried a high frequency of somatic mutations. With the exception of a mAb that bound to the HA globular head, all heterosubtypic mAbs bound to acid- sensitive epitopes in the HA stem region. Four mAbs were evaluated in vivo and protected mice from challenge with influenza viruses representative of different subtypes. These findings reveal that seasonal influenza vaccination can induce polyclonal heterosubtypic neutralizing antibodies that cross-react with the swine-origin pandemic H1N1 influenza virus and with the highly pathogenic H5N1 virus.
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Medicine
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https://n2t.net/ark:/12658/srd1318951
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