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

TitleHemagglutinin stalk-based universal vaccine constructs protect against group 2 influenza A viruses.
Publication TypeJournal Article
Year of Publication2013
AuthorsMargine I, Krammer F, Hai R, Heaton NS, Tan GS, Andrews SA, Runstadler JA, Wilson PC, Albrecht RA, GarcĂ­a-Sastre A, Palese P
JournalJ Virol
Volume87
Issue19
Pagination10435-46
Date Published2013 Oct
ISSN1098-5514
KeywordsAnimals, Antibodies, Neutralizing, Antibodies, Viral, Antibody Specificity, Cells, Cultured, Cross Reactions, Enzyme-Linked Immunosorbent Assay, Female, Fluorescent Antibody Technique, Genetic Vectors, Hemagglutinin Glycoproteins, Influenza Virus, Humans, Influenza A virus, Influenza Vaccines, Kidney, Mice, Mice, Inbred BALB C, Orthomyxoviridae Infections, Phylogeny
Abstract

<p>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.</p>

DOI10.1128/JVI.01715-13
Alternate JournalJ. Virol.
PubMed ID23903831
PubMed Central IDPMC3807421
Grant ListT32 AI007647 / AI / NIAID NIH HHS / United States
1P01AI097092-01A1 / AI / NIAID NIH HHS / United States
T32 AI07647-13 / AI / NIAID NIH HHS / United States
P01 AI097092 / AI / NIAID NIH HHS / United States
HHNSN266200700010C / NS / NINDS NIH HHS / United States