Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine

Corti, Davide; Suguitan Jr., Amorsolo; Pinna, Debora; Silacci, Chiara; Fernandez-Rodriguez, Blanca M.; Vanzetta, Fabrizia; Santos, Celia; Luke, Catherine J.; Torres-Velez, Fernando J.; Temperton, Nigel J.; Weiss, Robin A.; Sallusto, Federica; Subbarao, Kanta; Lanzavecchia, Antonio

doi:10.1172/JCI41902

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Journal article

Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine

Corti, Davide Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Suguitan Jr., Amorsolo Laboratory of Infectious Diseases, NIAID, NIH, Rockville, Maryland, USA
Pinna, Debora Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Silacci, Chiara Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Fernandez-Rodriguez, Blanca M. Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Vanzetta, Fabrizia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Santos, Celia Laboratory of Infectious Diseases, NIAID, NIH, Rockville, Maryland, USA
Luke, Catherine J. Laboratory of Infectious Diseases, NIAID, NIH, Rockville, Maryland, USA
Torres-Velez, Fernando J. Comparative Medicine Branch, NIAID, NIH, Rockville, Maryland, USA
Temperton, Nigel J. MRC/UCL Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom
Weiss, Robin A. MRC/UCL Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom
Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Subbarao, Kanta Laboratory of Infectious Diseases, NIAID, NIH, Rockville, Maryland, USA
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland

12.04.2010

Published in:

The Journal of clinical investigation. - 2010, vol. 120, no. 5, p. 1663-1673

Infectious disease

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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