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J Virol. Hemagglutinin Stalk-Based Universal Vaccine Constructs Protect Against Group 2 Influenza A Viruses
[Source: Journal of Virology, full page: (LINK). Abstract, edited.]
Hemagglutinin Stalk-Based Universal Vaccine Constructs Protect Against Group 2 Influenza A Viruses
I. Margine 1,2, F. Krammer 1*, R. Hai 1, N.S. Heaton 1, G.S. Tan 1, S.A. Andrews 6, J.A. Runstadler 5, P.C. Wilson 6, R.A. Albrecht 1,3, A. Garc?a-Sastre 1,3,4 and P. Palese 1,4*
Author Affiliations: 1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 5Department of Biological Engineering and Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA; 6Department of Medicine, The University of Chicago, Chicago, IL, USA
Published ahead of print 31 July 2013, doi: 10.1128/JVI.01715-13 - JVI.01715-13
ABSTRACT
Current influenza virus vaccines contain H1N1 (phylogenetic group 1 hemagglutinin), H3N2 (phylogenetic group 2 hemagglutinin) and influenza B virus components. These vaccines induce good protection against closely matched strains by predominantly eliciting antibodies against the membrane distal globular head domain of their respective viral hemagglutinins. This domain, however, undergoes rapid antigenic drift allowing the virus to escape neutralizing antibody responses. The membrane proximal stalk domain of the hemagglutinin is much more conserved as compared to the head domain. In recent years, a growing collection of antibodies that neutralize a broad range of influenza virus strains and subtypes by binding to this domain, has been isolated. Here we demonstrate that a vaccination strategy based on the stalk domain of the H3 hemagglutinin (group 2) induces in mice broadly neutralizing anti-stalk antibodies that are highly crossreactive to heterologous H3, H10, H14, H15 and H7 (derived from the novel Chinese H7N9 virus) hemagglutinins. Furthermore, we demonstrate that these antibodies confer broad protection against influenza viruses expressing various group 2 hemagglutinins including an H7 subtype. Through passive transfer experiments, we show that the protection is mainly mediated by neutralizing antibodies against the stalk domain. Our data suggest that in mice a vaccine strategy based on the hemagglutinin stalk domain can protect against viruses expressing divergent group 2 hemagglutinins.
FOOTNOTES
*To whom correspondence should be addressed: florian.krammer@mssm.edu
*peter.palese@mssm.edu
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
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Hemagglutinin Stalk-Based Universal Vaccine Constructs Protect Against Group 2 Influenza A Viruses
I. Margine 1,2, F. Krammer 1*, R. Hai 1, N.S. Heaton 1, G.S. Tan 1, S.A. Andrews 6, J.A. Runstadler 5, P.C. Wilson 6, R.A. Albrecht 1,3, A. Garc?a-Sastre 1,3,4 and P. Palese 1,4*
Author Affiliations: 1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 5Department of Biological Engineering and Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA; 6Department of Medicine, The University of Chicago, Chicago, IL, USA
Published ahead of print 31 July 2013, doi: 10.1128/JVI.01715-13 - JVI.01715-13
ABSTRACT
Current influenza virus vaccines contain H1N1 (phylogenetic group 1 hemagglutinin), H3N2 (phylogenetic group 2 hemagglutinin) and influenza B virus components. These vaccines induce good protection against closely matched strains by predominantly eliciting antibodies against the membrane distal globular head domain of their respective viral hemagglutinins. This domain, however, undergoes rapid antigenic drift allowing the virus to escape neutralizing antibody responses. The membrane proximal stalk domain of the hemagglutinin is much more conserved as compared to the head domain. In recent years, a growing collection of antibodies that neutralize a broad range of influenza virus strains and subtypes by binding to this domain, has been isolated. Here we demonstrate that a vaccination strategy based on the stalk domain of the H3 hemagglutinin (group 2) induces in mice broadly neutralizing anti-stalk antibodies that are highly crossreactive to heterologous H3, H10, H14, H15 and H7 (derived from the novel Chinese H7N9 virus) hemagglutinins. Furthermore, we demonstrate that these antibodies confer broad protection against influenza viruses expressing various group 2 hemagglutinins including an H7 subtype. Through passive transfer experiments, we show that the protection is mainly mediated by neutralizing antibodies against the stalk domain. Our data suggest that in mice a vaccine strategy based on the hemagglutinin stalk domain can protect against viruses expressing divergent group 2 hemagglutinins.
FOOTNOTES
*To whom correspondence should be addressed: florian.krammer@mssm.edu
*peter.palese@mssm.edu
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
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