Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1.
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.
Nandi
Avishek
A
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, E/CLS-1011, 3 Blackfan Circle, Boston, MA 02215, USA.
Lavine
Christine L
CL
Wang
Pengcheng
P
Lipchina
Inna
I
Goepfert
Paul A
PA
Shaw
George M
GM
Tomaras
Georgia D
GD
Montefiori
David C
DC
Haynes
Barton F
BF
Easterbrook
Philippa
P
Robinson
James E
JE
Sodroski
Joseph G
JG
Yang
Xinzhen
X
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
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