期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 44, 页码 18979-18984出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1013387107
关键词
mice; pandemic; synthetic peptide; vaccine; HA2
资金
- National Institutes of Health (NIH) [UO1 AI070469, T32 AI007647, AI058113]
- Center for Research on Influenza Pathogenesis [HHSN2662000700010C]
- Development of A Universal Influenza Virus Vaccine [1RC1 AI086061-01]
- Northeast Biodefense Center [U54 AI057158-04]
- NIH/National Institute of Allergy and Infectious Diseases [R01 AI0401111, HHSN266200500028C]
- Mount Sinai Medical Scientists Training [T32 GM007280]
- Skaggs Institute for Chemical Biology
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 a-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.
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