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Conserved epitope on influenza-virus hemagglutinin head defined by a vaccine-induced antibody.

Publication ,  Journal Article
Raymond, DD; Bajic, G; Ferdman, J; Suphaphiphat, P; Settembre, EC; Moody, MA; Schmidt, AG; Harrison, SC
Published in: Proc Natl Acad Sci U S A
January 2, 2018

Circulating influenza viruses evade neutralization in their human hosts by acquiring escape mutations at epitopes of prevalent antibodies. A goal for next-generation influenza vaccines is to reduce escape likelihood by selectively eliciting antibodies recognizing conserved surfaces on the viral hemagglutinin (HA). The receptor-binding site (RBS) on the HA "head" and a region near the fusion peptide on the HA "stem" are two such sites. We describe here a human antibody clonal lineage, designated CL6649, members of which bind a third conserved site ("lateral patch") on the side of the H1-subtype, HA head. A crystal structure of HA with bound Fab6649 shows the conserved antibody footprint. The site was invariant in isolates from 1977 (seasonal) to 2012 (pdm2009); antibodies in CL6649 recognize HAs from the entire period. In 2013, human H1 viruses acquired mutations in this epitope that were retained in subsequent seasons, prompting modification of the H1 vaccine component in 2017. The mutations inhibit Fab6649 binding. We infer from the rapid spread of these mutations in circulating H1 influenza viruses that the previously subdominant, conserved lateral patch had become immunodominant for individuals with B-cell memory imprinted by earlier H1 exposure. We suggest that introduction of the pdm2009 H1 virus, to which most of the broadly prevalent, neutralizing antibodies did not bind, conferred a selective advantage in the immune systems of infected hosts to recall of memory B cells that recognized the lateral patch, the principal exposed epitope that did not change when pdm2009 displaced previous seasonal H1 viruses.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 2, 2018

Volume

115

Issue

1

Start / End Page

168 / 173

Location

United States

Related Subject Headings

  • Influenza Vaccines
  • Immunologic Memory
  • Humans
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Epitopes
  • Antibodies, Viral
  • Antibodies, Monoclonal
 

Citation

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Raymond, D. D., Bajic, G., Ferdman, J., Suphaphiphat, P., Settembre, E. C., Moody, M. A., … Harrison, S. C. (2018). Conserved epitope on influenza-virus hemagglutinin head defined by a vaccine-induced antibody. Proc Natl Acad Sci U S A, 115(1), 168–173. https://doi.org/10.1073/pnas.1715471115
Raymond, Donald D., Goran Bajic, Jack Ferdman, Pirada Suphaphiphat, Ethan C. Settembre, M Anthony Moody, Aaron G. Schmidt, and Stephen C. Harrison. “Conserved epitope on influenza-virus hemagglutinin head defined by a vaccine-induced antibody.Proc Natl Acad Sci U S A 115, no. 1 (January 2, 2018): 168–73. https://doi.org/10.1073/pnas.1715471115.
Raymond DD, Bajic G, Ferdman J, Suphaphiphat P, Settembre EC, Moody MA, et al. Conserved epitope on influenza-virus hemagglutinin head defined by a vaccine-induced antibody. Proc Natl Acad Sci U S A. 2018 Jan 2;115(1):168–73.
Raymond, Donald D., et al. “Conserved epitope on influenza-virus hemagglutinin head defined by a vaccine-induced antibody.Proc Natl Acad Sci U S A, vol. 115, no. 1, Jan. 2018, pp. 168–73. Pubmed, doi:10.1073/pnas.1715471115.
Raymond DD, Bajic G, Ferdman J, Suphaphiphat P, Settembre EC, Moody MA, Schmidt AG, Harrison SC. Conserved epitope on influenza-virus hemagglutinin head defined by a vaccine-induced antibody. Proc Natl Acad Sci U S A. 2018 Jan 2;115(1):168–173.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 2, 2018

Volume

115

Issue

1

Start / End Page

168 / 173

Location

United States

Related Subject Headings

  • Influenza Vaccines
  • Immunologic Memory
  • Humans
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Epitopes
  • Antibodies, Viral
  • Antibodies, Monoclonal