Corti, Davide and Suguitan Jr., Amorsolo L. and Pinna, Debora and Silacci, Chiara and Fernandez-Rodriguez, Blanca M. and Vanzetta, Fabrizia and Santos, Celia and Luke, Catherine J. and Torres-Velez, Fernando J. and Temperton, Nigel J. and Weiss, Robin A. and Sallusto, Federica and Subbarao, Kanta and Lanzavecchia, Antonio (2010) Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine. Journal of Clinical Investigation, 120 (5). pp. 1663-1673. ISSN 0021-9738. (doi:10.1172/JCI41902) (Full text available)
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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.
|Uncontrolled keywords:||epitope, FB110 monoclonal antibody, FE17 monoclonal antibody, FE43 monoclonal antibody, immunoglobulin G, influenza vaccine, monoclonal antibody, neutralizing antibody, unclassified drug, animal cell, animal experiment, animal tissue, antibody production, antibody response, antigen antibody reaction, article, B lymphocyte, cell immortalization, controlled study, female, human, human cell, influenza, influenza vaccination, Influenza virus A H1N1, Influenza virus A H3N2, Influenza virus A H5N1, Influenza virus A H9N2, mouse, nonhuman, priority journal, somatic mutation, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Binding Sites, Dogs, Epitope Mapping, Female, Humans, Immunoglobulin G, Influenza Vaccines, Influenza, Human, Leukocytes, Mononuclear, Mice, Mice, Inbred BALB C, Mutation, Orthomyxoviridae, Protein Binding|
|Subjects:||Q Science > QR Microbiology > QR355 Virology|
|Divisions:||Faculties > Science Technology and Medical Studies > Medway School of Pharmacy|
|Depositing User:||Nigel Temperton|
|Date Deposited:||02 Aug 2012 07:03|
|Last Modified:||10 Jun 2014 08:13|
|Resource URI:||https://kar.kent.ac.uk/id/eprint/29399 (The current URI for this page, for reference purposes)|
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