Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin.

Journal Article (Journal Article)

Seasonal antigenic drift of circulating influenza virus leads to a requirement for frequent changes in vaccine composition, because exposure or vaccination elicits human antibodies with limited cross-neutralization of drifted strains. We describe a human monoclonal antibody, CH65, obtained by isolating rearranged heavy- and light-chain genes from sorted single plasma cells, coming from a subject immunized with the 2007 trivalent influenza vaccine. The crystal structure of a complex of the hemagglutinin (HA) from H1N1 strain A/Solomon Islands/3/2006 with the Fab of CH65 shows that the tip of the CH65 heavy-chain complementarity determining region 3 (CDR3) inserts into the receptor binding pocket on HA1, mimicking in many respects the interaction of the physiological receptor, sialic acid. CH65 neutralizes infectivity of 30 out of 36 H1N1 strains tested. The resistant strains have a single-residue insertion near the rim of the sialic-acid pocket. We conclude that broad neutralization of influenza virus can be achieved by antibodies with contacts that mimic those of the receptor.

Full Text

Duke Authors

Cited Authors

  • Whittle, JRR; Zhang, R; Khurana, S; King, LR; Manischewitz, J; Golding, H; Dormitzer, PR; Haynes, BF; Walter, EB; Moody, MA; Kepler, TB; Liao, H-X; Harrison, SC

Published Date

  • August 23, 2011

Published In

Volume / Issue

  • 108 / 34

Start / End Page

  • 14216 - 14221

PubMed ID

  • 21825125

Pubmed Central ID

  • PMC3161572

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1111497108


  • eng

Conference Location

  • United States