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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
The development of CD4 binding site antibodies during HIV-1 infection
Journal of Virology, Volume 86, No. 14, Year 2012
Notification
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Description
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. © 2012, American Society for Microbiology.
Authors & Co-Authors
Lynch, Rebecca M.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Tran, Lillian
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Louder, Mark K.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Schmidt, Stephen D.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Cohen, Myron S.
United States, Chapel Hill
Unc School of Medicine
DerSimonian, Rebecca R.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Euler, Zelda
Netherlands, Amsterdam
Universiteit Van Amsterdam
Gray, Elin Solomonovna
South Africa, Johannesburg
National Institute for Communicable Diseases
South Africa, Johannesburg
University of the Witwatersrand
Abdool Karim, Salim S.
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Kirchherr, Jennifer L.
United States, Durham
Duke University Medical Center
Montefiori, David Charles
United States, Durham
Duke University Medical Center
Sibeko, Sengeziwe Sibongile
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Soderberg, Kelly A.
United States, Durham
Duke University Medical Center
Tomaras, Georgia D.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Yang, Zhi Yong
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Nabel, Gary J.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Schuitemaker, Hanneke
Netherlands, Amsterdam
Universiteit Van Amsterdam
Morris, Lynn
South Africa, Johannesburg
National Institute for Communicable Diseases
South Africa, Johannesburg
University of the Witwatersrand
Haynes, Barton F.
United States, Durham
Duke University Medical Center
Mascola, John R.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Statistics
Citations: 131
Authors: 20
Affiliations: 7
Identifiers
Doi:
10.1128/JVI.00734-12
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Infectious Diseases
Study Design
Cross Sectional Study
Cohort Study