title: Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals.
abstract: A small proportion of HIV-infected individuals generate a neutralizing antibody (NAb) response of exceptional magnitude and breadth. A detailed analysis of the critical epitopes targeted by broadly neutralizing antibodies should help to define optimal targets for vaccine design. HIV-1-infected subjects with potent cross-reactive serum neutralizing antibodies were identified by assaying sera from 308 subjects against a multiclade panel of 12 "tier 2" viruses (4 each of subtypes A, B, and C). Various neutralizing epitope specificities were determined for the top 9 neutralizers, including clade A-, clade B-, clade C-, and clade A/C-infected donors, by using a comprehensive set of assays. In some subjects, neutralization breadth was mediated by two or more antibody specificities. Although antibodies to the gp41 membrane-proximal external region (MPER) were identified in some subjects, the subjects with the greatest neutralization breadth targeted gp120 epitopes, including the CD4 binding site, a glycan-containing quaternary epitope formed by the V2 and V3 loops, or an outer domain epitope containing a glycan at residue N332. The broadly reactive HIV-1 neutralization observed in some subjects is mediated by antibodies targeting several conserved regions on the HIV-1 envelope glycoprotein.
authors.affiliation: Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center, Box 2926, Durham, NC 27710, USA. gdt@duke.edu
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: James M
authors.initials: JM
authors.lastname: Binley
authors.forename: Elin S
authors.initials: ES
authors.lastname: Gray
authors.forename: Emma T
authors.initials: ET
authors.lastname: Crooks
authors.forename: Keiko
authors.initials: K
authors.lastname: Osawa
authors.forename: Penny L
authors.initials: PL
authors.lastname: Moore
authors.forename: Nancy
authors.initials: N
authors.lastname: Tumba
authors.forename: Tommy
authors.initials: T
authors.lastname: Tong
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Yates
authors.forename: Julie
authors.initials: J
authors.lastname: Decker
authors.forename: Constantinos Kurt
authors.initials: CK
authors.lastname: Wibmer
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
authors.forename: Salim
authors.initials: S
authors.lastname: Abdool Karim
authors.forename: Gift
authors.initials: G
authors.lastname: Kamanga
authors.forename: John A
authors.initials: JA
authors.lastname: Crump
authors.forename: Myron
authors.initials: M
authors.lastname: Cohen
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans
chemical_list: D057134:Antibodies, Neutralizing; D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; C514793:gp120 protein, Human immunodeficiency virus 1; C514787:gp41 protein, Human immunodeficiency virus 1