Hemagglutinin stalk-based universal vaccine constructs protect against group 2 influenza A viruses.

Published

Journal Article

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 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 cross-reactive 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 mediated mainly 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.

Full Text

Duke Authors

Cited Authors

  • Margine, I; Krammer, F; Hai, R; Heaton, NS; Tan, GS; Andrews, SA; Runstadler, JA; Wilson, PC; Albrecht, RA; García-Sastre, A; Palese, P

Published Date

  • October 2013

Published In

Volume / Issue

  • 87 / 19

Start / End Page

  • 10435 - 10446

PubMed ID

  • 23903831

Pubmed Central ID

  • 23903831

Electronic International Standard Serial Number (EISSN)

  • 1098-5514

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/JVI.01715-13

Language

  • eng