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Vaccine-elicited antibody that neutralizes H5N1 influenza and variants binds the receptor site and polymorphic sites

Winarski, Katie L., Thornburg, Natalie J., Yu, Yingchun, Sapparapu, Gopal, Crowe, James. E., Spiller, Benjamin W.
Proceedings of the National Academy of Sciences of the United States of America 2015 v.112 no.30 pp. 9346-9351
Influenza A virus, aerosols, antibodies, birds, ferrets, hemagglutinins, human diseases, immune response, influenza, models, mutation, neutralization, vaccines
A small number of mutations to the viral hemagglutinin are sufficient to permit aerosol transmission, in a ferret model of human infection, of highly pathogenic avian H5N1 influenza A viruses. Here, we show how an antibody (H5.3) against hemagglutinin 5 (H5) recognizes both WT and variant H5 proteins. H5.3 retains germ-line characteristics, most remarkably a conformationally flexible combining site, consistent with an antibody that has not been through multiple cycles of affinity maturation. Many antibodies against H5 are lightly mutated and may arise from naive B cells, explaining the low antigenicity of H5N1 vaccines relative to seasonal influenza vaccines and supporting the idea that multiple exposures are necessary to develop a strong immune response to H5N1 strains.