title: Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1.
abstract: Neutralizing antibody (nAb) response is sporadic and has limited potency and breadth during infection with human immunodeficiency virus type 1 (HIV-1). In rare cases, broad and potent nAbs are actually induced in vivo. Identifying specific epitopes targeted by such broad and potent nAb response is valuable in guiding the design of a prophylactic vaccine aimed to induce nAb. In this study, we have defined neutralizing epitope usage in 7 out of 17 subjects with broad and potent nAbs by using targeted mutagenesis in known neutralizing epitopes of HIV-1 glycoproteins and by using in vitro depletion of serum neutralizing activity by various recombinant HIV-1 glycoproteins. Consistent with recent reports, the CD4 binding site (CD4BS) is targeted by nAbs in vivo (4 of the 7 subjects with defined neutralizing epitopes). The new finding from this study is that epitopes in the gp120 outer domain are also targeted by nAbs in vivo (5 of the 7 subjects). The outer domain epitopes include glycan-dependent epitopes (2 subjects), conserved nonlinear epitope in the V3 region (2 subjects), and a CD4BS epitope composed mainly of the elements in the outer domain (1 subject). Importantly, we found indication for epitope poly-specificity, a dual usage of the V3 and CD4BS epitopes, in only one subject. This study provides a more complete profile of epitope usage for broad and potent nAb responses during HIV-1 infection.
authors.affiliation: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, E/CLS-1011, 3 Blackfan Circle, Boston, MA 02215, USA.
authors.forename: Avishek
authors.initials: A
authors.lastname: Nandi
authors.forename: Christine L
authors.initials: CL
authors.lastname: Lavine
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Wang
authors.forename: Inna
authors.initials: I
authors.lastname: Lipchina
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
authors.forename: James E
authors.initials: JE
authors.lastname: Robinson
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Sodroski
authors.forename: Xinzhen
authors.initials: X
authors.lastname: Yang
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; C514793:gp120 protein, Human immunodeficiency virus 1