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

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

Davide Corti1, Amorsolo L. Suguitan, Jr.2, Debora Pinna1, Chiara Silacci1, Blanca M. Fernandez-Rodriguez1, Fabrizia Vanzetta1, Celia Santos2, Catherine J. Luke2, Fernando J. Torres-Velez3, Nigel J. Temperton4, Robin A. Weiss4, Federica Sallusto1, Kanta Subbarao2 and Antonio Lanzavecchia1

1Institute for Research in Biomedicine, Bellinzona, Switzerland.
2Laboratory of Infectious Diseases and
3Comparative Medicine Branch, NIAID, NIH, Rockville, Maryland, USA.
4MRC/UCL Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom.

Address correspondence to: Antonio Lanzavecchia, Institute for Research in Biomedicine, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland. Phone: 41.91.8200310; Fax: 41.91.8200312; E-mail: lanzavecchia@irb.unisi.ch.

Authorship note: Davide Corti and Amorsolo L. Suguitan Jr. contributed equally to this work.

Published April 12, 2010
Received for publication December 1, 2009, and accepted in revised form February 17, 2010.

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.


http://www.jci.org/articles/view/41902?key=10140cb74438512dec4a

 

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

Study: Seasonal flu vaccine may induce broadly cross-reactive antibodies
An international team of researchers reports today that individuals who received seasonal influenza vaccine produced antibodies that, when tested in lab cultures and in mice, neutralized flu viruses of several different subtypes, including pandemic H1N1 and avian H5N1. Using memory B cells from four vaccinated individuals, the researchers isolated 20 monoclonal antibodies that bound and neutralized flu viruses of the H1, H2, H5, H6, and H9 subtypes, including pandemic H1N1, in in-vitro experiments. The researchers then injected groups of mice with two of these antibodies and later infected the mice with usually lethal doses of one of four virus subtypes: a seasonal H1N1 and the avian subtypes H6N1, H5N1, and H7N7. The antibodies gave the mice full or partial protection against all of these viruses except the H7N7. Writing in the Journal of Clinical Investigation, the authors say that further studies will be needed in animals and eventually in humans to determine if the antibodies could have a role in preventing or treating flu infections. They note that even in "high responder" individuals, cross-reactive antibodies rarely reach effective neutralizing concentrations in serum.


http://www.cidrap.umn.edu/cidrap/content/other/news/apr1210newscan.html