Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine
Davide Corti, … , Kanta Subbarao, Antonio Lanzavecchia
Davide Corti, … , Kanta Subbarao, Antonio Lanzavecchia
Published April 12, 2010
Citation Information: J Clin Invest. 2010;120(5):1663-1673. https://doi.org/10.1172/JCI41902.
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Research Article Infectious disease

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

Abstract

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.

Authors

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

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Figure 1

Vaccine-binding and H5 pseudotype-neutralizing antibodies in plasma samples collected before and after seasonal influenza vaccination.

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Vaccine-binding and H5 pseudotype-neutralizing antibodies in plasma samp...
Volunteers (A to X) were immunized with seasonal influenza vaccine in 2 consecutive seasons. Plasma and PBMC samples were collected before and 2 weeks after vaccination. (A and B) Vaccine-specific IgG was measured in plasma by ELISA using the homologous vaccine as antigen. Reciprocal EC50 values before (white bars) and after vaccination (black bars) in 2007 (A) and 2008 seasons (B) are shown. (C and D) H5-specific neutralizing titers were measured in the same plasma samples by a pseudotyped neutralization assay against an H5 pseudovirus (A/VN/1194/04). Reciprocal ID50 values before (white bars) and after vaccination (black bars) in 2007 (C) and 2008 (D) are shown. (E and F) Correlation between the increase of vaccine binding titers (E) and H5-neutralizing titers (F) following vaccination in 2007 (x axis) and 2008 (y axis) in the 9 donors that received the seasonal influenza vaccine for the 2 consecutive years.