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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 34; pp. 14216 - 14221
• Main Authors: Whittle, James R. R, Zhang, Ruijun, Khurana, Surender, King, Lisa R, Manischewitz, Jody, Golding, Hana, Dormitzer, Philip R, Haynes, Barton F, Walter, Emmanuel B, Moody, M. Anthony, Kepler, Thomas B, Liao, Hua-Xin, Harrison, Stephen C
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 23.08.2011; National Acad Sciences
• Subjects: 60 APPLIED LIFE SCIENCES; Amino Acid Sequence; ANTIBODIES; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - chemistry; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antibody Affinity - immunology; Antibody Specificity - immunology; Antigenic drift; antigenic variation; BASIC BIOLOGICAL SCIENCES; Binding Sites; Biological Sciences; Cells; Complementarity Determining Regions - chemistry; Complementarity Determining Regions - immunology; complementarity-determining region 3; CRYSTAL STRUCTURE; Fab; GENES; Genetic mutation; Glycosylation; H1N1 subtype influenza A virus; Hemagglutinin Glycoproteins, Influenza Virus - immunology; HEMAGGLUTININS; Humans; Hydrogen bonds; Immunization; INFECTIVITY; INFLUENZA; Influenza A virus; Influenza A Virus, H1N1 Subtype - immunology; Influenza virus; Insertion; Islands; Mimicry; Models, Molecular; Molecular Sequence Data; Monoclonal antibodies; Neutralization; Orthomyxoviridae; pathogenicity; Phylogeny; PLASMA CELLS; Polysaccharides; Protein Binding; Receptors; Receptors, Virus - immunology; SIALIC ACID; Sialic acids; STRAINS; Vaccination; VACCINES; Viruses
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1111497108

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.