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Isolation of a Monoclonal Antibody That Targets the Alpha-2 Helix of gp120 and Represents the Initial Autologous Neutralizing-Antibody Response in an HIV-1 Subtype C-Infected Individual

Elin S. Gray; M. Anthony Moody; Constantinos Kurt Wibmer; Xi Chen; Dawn J. Marshall; Joshua Amos; Penny L. Moore; Andrew Foulger; Jae-Sung Yu; Bronwen E. Lambson; Salim Abdool Karim; John Whitesides; Georgia D. Tomaras; Barton F. Haynes; Lynn Morris; Hua-Xin Liao

Title:
Isolation of a Monoclonal Antibody That Targets the Alpha-2 Helix of gp120 and Represents the Initial Autologous Neutralizing-Antibody Response in an HIV-1 Subtype C-Infected Individual
Author(s):
Gray, Elin S.
Moody, M. Anthony
Wibmer, Constantinos Kurt
Chen, Xi
Marshall, Dawn J.
Amos, Joshua
Moore, Penny L.
Foulger, Andrew
Yu, Jae-Sung
Lambson, Bronwen E.
Abdool Karim, Salim
Whitesides, John
Tomaras, Georgia D.
Haynes, Barton F.
Morris, Lynn
Liao, Hua-Xin
Date:
Type:
Articles
Department:
Epidemiology
Volume:
85
Permanent URL:
Book/Journal Title:
Journal of Virology
Abstract:
The C3-V4 region is a major target of autologous neutralizing antibodies in HIV-1 subtype C infection. We previously identified a Center for AIDS Program of Research in South Africa (CAPRISA) participant, CAP88, who developed a potent neutralizing-antibody response within 3 months of infection that targeted an epitope in the C3 region of the HIV-1 envelope (P. L. Moore et al., PLoS Pathog. 5:e1000598, 2009). Here we showed that these type-specific antibodies could be adsorbed using recombinant gp120 from the transmitted/founder virus from CAP88 but not by gp120 made from other isolates. Furthermore, this activity could be depleted using a chimeric gp120 protein that contained only the C3 region from the CAP88 viral envelope engrafted onto the unrelated CAP63 viral envelope (called 63-88C3). On the basis of this, a differential sorting of memory B cells was performed using gp120s made from 63-88C3 and CAP63 labeled with different fluorochromes as positive and negative probes, respectively. This strategy resulted in the isolation of a highly specific monoclonal antibody (MAb), called CAP88-CH06, that neutralized the CAP88 transmitted/founder virus and viruses from acute infection but was unable to neutralize CAP88 viruses isolated at 6 and 12 months postinfection. The latter viruses contained 2 amino acid changes in the alpha-2 helix of C3 that mediated escape from this MAb. One of these changes involved the introduction of an N-linked glycan at position 339 that occluded the epitope, while the other mutation (either E343K or E350K) was a charge change. Our data validate the use of differential sorting to isolate a MAb targeting a specific epitope in the envelope glycoprotein and provided insights into the mechanisms of autologous neutralization escape.
Subject(s):
Virology
Epidemiology
Publisher DOI:
10.1128/JVI.00563-11
Item views:
103
Metadata:
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