Vaccine-elicited antibody that neutralizes H5N1 influenza and variants binds the receptor site and polymorphic sites
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 13, 2015
- Source ID
- 10.1073/pnas.1502762112
Entities
People
- Benjamin W. Spiller
- Gopal Sapparapu
- James E. Crowe, Jr.
- Katie L. Winarski
- Natalie J. Thornburg
- Yingchun Yu
Organizations
- Defense Threat Reduction Agency
- Office of Extramural Research
- Vanderbilt University