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Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes

Academic Article
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Overview

related to degree

  • Ekiert, Damian, Ph.D. in Chemical Biology, Scripps Research 2006 - 2011

authors

  • Wang, T. T.
  • Tan, G. S.
  • Hai, R.
  • Pica, N.
  • Ngai, L.
  • Ekiert, Damian
  • Wilson, Ian
  • Garcia-Sastre, A.
  • Moran, T. M.
  • Palese, P.

publication date

  • November 2010

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Current influenza virus vaccines protect mostly against homologous virus strains; thus, regular immunization with updated vaccine formulations is necessary to guard against the virus' hallmark remodeling of regions that mediate neutralization. Development of a broadly protective influenza vaccine would mark a significant advance in human infectious diseases research. Antibodies with broad neutralizing activity (nAbs) against multiple influenza virus strains or subtypes have been reported to bind the stalk of the viral hemagglutinin, suggesting that a vaccine based on this region could elicit a broadly protective immune response. Here we describe a hemagglutinin subunit 2 protein (HA2)-based synthetic peptide vaccine that provides protection in mice against influenza viruses of the structurally divergent subtypes H3N2, H1N1, and H5N1. The immunogen is based on the binding site of the recently described nAb 12D1, which neutralizes H3 subtype viruses, demonstrates protective activity in vivo, and, in contrast to a majority of described nAbs, appears to bind to residues within a single α-helical portion of the HA2 protein. Our data further demonstrate that the specific design of our immunogen is integral in the induction of broadly active anti-hemagglutinin antibodies. These results provide proof of concept for an HA2-based influenza vaccine that could diminish the threat of pandemic influenza disease and generally reduce the significance of influenza viruses as human pathogens.

subject areas

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Hemagglutinins, Viral
  • Humans
  • Immunization
  • Influenza A virus
  • Influenza Vaccines
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections
  • Peptides
  • Protein Structure, Secondary
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Research

keywords

  • HA2
  • mice
  • pandemic
  • synthetic peptide
  • vaccine
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Identity

PubMed Central ID

  • PMC2973924

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1013387107

PubMed ID

  • 20956293
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Additional Document Info

start page

  • 18979

end page

  • 18984

volume

  • 107

issue

  • 44

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