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.
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Date
2011
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Microbiology.
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.
Description
Keywords
HIV antibodies., HIV infections--Immunology., Antibodies, Monoclonal.
Citation
Gray E.S., et al. 2011. 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. J. Virol. 85 (15), pp.7719–7729.