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

Abstract

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.

Authors:
; ; ; ; ; ; ; ; ; ; ; ;  [1];  [2];  [2];  [2]
  1. (Harvard-Med)
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIHHHMINIAID
OSTI Identifier:
1024052
Resource Type:
Journal Article
Journal Name:
Proc. Natl. Acad. Sci. USA
Additional Journal Information:
Journal Volume: 108; Journal Issue: (34) ; 08, 2011; Journal ID: ISSN 1091-6490
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ANTIBODIES; CRYSTAL STRUCTURE; GENES; HEMAGGLUTININS; INFECTIVITY; INFLUENZA; PLASMA CELLS; SIALIC ACID; STRAINS; VACCINES

Citation Formats

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., Novartis), US-FDA), and Duke). Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. United States: N. p., 2011. Web. doi:10.1073/pnas.1111497108.
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., Novartis), US-FDA), & Duke). Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. United States. doi:10.1073/pnas.1111497108.
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., Novartis), US-FDA), and Duke). Tue . "Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin". United States. doi:10.1073/pnas.1111497108.
@article{osti_1024052,
title = {Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin},
author = {Whittle, James R.R. and Zhang, Ruijun and Khurana, Surender and King, Lisa R. and Manischewitz, Jody and Golding, Hana and Dormitzer, Philip R. and Haynes, Barton F. and Walter, Emmanuel B. and Moody, M. Anthony and Kepler, Thomas B. and Liao, Hua-Xin and Harrison, Stephen C. and Novartis) and US-FDA) and Duke)},
abstractNote = {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.},
doi = {10.1073/pnas.1111497108},
journal = {Proc. Natl. Acad. Sci. USA},
issn = {1091-6490},
number = (34) ; 08, 2011,
volume = 108,
place = {United States},
year = {2011},
month = {9}
}