Skip to main content

The development of CD4 binding site antibodies during HIV-1 infection.

Publication ,  Journal Article
Lynch, RM; Tran, L; Louder, MK; Schmidt, SD; Cohen, M; CHAVI 001 Clinical Team Members; Dersimonian, R; Euler, Z; Gray, ES; Abdool Karim, S ...
Published in: J Virol
July 2012

Broadly neutralizing antibodies to the CD4 binding site (CD4bs) of gp120 are generated by some HIV-1-infected individuals, but little is known about the prevalence and evolution of this antibody response during the course of HIV-1 infection. We analyzed the sera of 113 HIV-1 seroconverters from three cohorts for binding to a panel of gp120 core proteins and their corresponding CD4bs knockout mutants. Among sera collected between 99 and 258 weeks post-HIV-1 infection, 88% contained antibodies to the CD4bs and 47% contained antibodies to resurfaced stabilized core (RSC) probes that react preferentially with broadly neutralizing CD4bs antibodies (BNCD4), such as monoclonal antibodies (MAbs) VRC01 and VRC-CH31. Analysis of longitudinal serum samples from a subset of 18 subjects revealed that CD4bs antibodies to gp120 arose within the first 4 to 16 weeks of infection, while the development of RSC-reactive antibodies was more varied, occurring between 10 and 152 weeks post-HIV-1 infection. Despite the presence of these antibodies, serum neutralization mediated by RSC-reactive antibodies was detected in sera from only a few donors infected for more than 3 years. Thus, CD4bs antibodies that bind a VRC01-like epitope are often induced during HIV-1 infection, but the level and potency required to mediate serum neutralization may take years to develop. An improved understanding of the immunological factors associated with the development and maturation of neutralizing CD4bs antibodies during HIV-1 infection may provide insights into the requirements for eliciting this response by vaccination.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

July 2012

Volume

86

Issue

14

Start / End Page

7588 / 7595

Location

United States

Related Subject Headings

  • Virology
  • Male
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Gene Knockout Techniques
  • Female
  • CD4 Antigens
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lynch, R. M., Tran, L., Louder, M. K., Schmidt, S. D., Cohen, M., CHAVI 001 Clinical Team Members, … Mascola, J. R. (2012). The development of CD4 binding site antibodies during HIV-1 infection. J Virol, 86(14), 7588–7595. https://doi.org/10.1128/JVI.00734-12
Lynch, Rebecca M., Lillian Tran, Mark K. Louder, Stephen D. Schmidt, Myron Cohen, CHAVI 001 Clinical Team Members, Rebecca Dersimonian, et al. “The development of CD4 binding site antibodies during HIV-1 infection.J Virol 86, no. 14 (July 2012): 7588–95. https://doi.org/10.1128/JVI.00734-12.
Lynch RM, Tran L, Louder MK, Schmidt SD, Cohen M, CHAVI 001 Clinical Team Members, et al. The development of CD4 binding site antibodies during HIV-1 infection. J Virol. 2012 Jul;86(14):7588–95.
Lynch, Rebecca M., et al. “The development of CD4 binding site antibodies during HIV-1 infection.J Virol, vol. 86, no. 14, July 2012, pp. 7588–95. Pubmed, doi:10.1128/JVI.00734-12.
Lynch RM, Tran L, Louder MK, Schmidt SD, Cohen M, CHAVI 001 Clinical Team Members, Dersimonian R, Euler Z, Gray ES, Abdool Karim S, Kirchherr J, Montefiori DC, Sibeko S, Soderberg K, Tomaras G, Yang Z-Y, Nabel GJ, Schuitemaker H, Morris L, Haynes BF, Mascola JR. The development of CD4 binding site antibodies during HIV-1 infection. J Virol. 2012 Jul;86(14):7588–7595.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

July 2012

Volume

86

Issue

14

Start / End Page

7588 / 7595

Location

United States

Related Subject Headings

  • Virology
  • Male
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Gene Knockout Techniques
  • Female
  • CD4 Antigens