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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
The neutralization breadth of HIV-1 develops incrementally over four years and is associated with CD4
+
T cell decline and high viral load during acute infection
Journal of Virology, Volume 85, No. 10, Year 2011
Notification
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Description
An understanding of how broadly neutralizing activity develops in HIV-1-infected individuals is needed to guide vaccine design and immunization strategies. Here we used a large panel of 44 HIV-1 envelope variants (subtypes A, B, and C) to evaluate the presence of broadly neutralizing antibodies in serum samples obtained 3 years after seroconversion from 40 women enrolled in the CAPRISA 002 acute infection cohort. Seven of 40 participants had serum antibodies that neutralized more than 40% of viruses tested and were considered to have neutralization breadth. Among the samples with breadth, CAP257 serum neutralized 82% (36/44 variants) of the panel, while CAP256 serum neutralized 77% (33/43 variants) of the panel. Analysis of longitudinal samples showed that breadth developed gradually starting from year 2, with the number of viruses neutralized as well as the antibody titer increasing over time. Interestingly, neutralization breadth peaked at 4 years postinfection, with no increase thereafter. The extent of cross-neutralizing activity correlated with CD4 + T cell decline, viral load, and CD4 + T cell count at 6 months postinfection but not at later time points, suggesting that early events set the stage for the development of breadth. However, in a multivariate analysis, CD4 decline was the major driver of this association, as viral load was not an independent predictor of breadth. Mapping of the epitopes targeted by cross-neutralizing antibodies revealed that in one individual these antibodies recognized the membrane-proximal external region (MPER), while in two other individuals, cross-neutralizing activity was adsorbed by monomeric gp120 and targeted epitopes that involved the N-linked glycan at position 332 in the C3 region. Serum antibodies from the other four participants targeted quaternary epitopes, at least 2 of which were PG9/16-like and depended on the N160 and/or L165 residue in the V2 region. These data indicate that fewer than 20% of HIV-1 subtype C-infected individuals develop antibodies with cross-neutralizing activity after 3 years of infection and that these antibodies target different regions of the HIV-1 envelope, including as yet uncharacterized epitopes. © 2011, American Society for Microbiology.
Authors & Co-Authors
Gray, Elin Solomonovna
South Africa, Johannesburg
National Institute for Communicable Diseases
Madiga, Maphuti Carol
South Africa, Johannesburg
National Institute for Communicable Diseases
Hermanus, Tandile
South Africa, Johannesburg
National Institute for Communicable Diseases
Moore, Penny L.
South Africa, Johannesburg
National Institute for Communicable Diseases
South Africa, Johannesburg
University of the Witwatersrand
Wibmer, Constantinos Kurt
South Africa, Johannesburg
National Institute for Communicable Diseases
South Africa, Johannesburg
University of the Witwatersrand
Tumba, Nancy L.
South Africa, Johannesburg
National Institute for Communicable Diseases
Werner, Lise
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Mlisana, Koleka P.
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Sibeko, Sengeziwe Sibongile
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Williamson, Carolyn
South Africa, Cape Town
University of Cape Town
Abdool Karim, Salim S.
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Morris, Lynn
South Africa, Johannesburg
National Institute for Communicable Diseases
South Africa, Johannesburg
University of the Witwatersrand
Statistics
Citations: 453
Authors: 12
Affiliations: 4
Identifiers
Doi:
10.1128/JVI.00198-11
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Infectious Diseases
Maternal And Child Health
Study Design
Cohort Study
Participants Gender
Female