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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Multiple pathways of escape from HIV broadly cross-neutralizing V2-dependent antibodies
Journal of Virology, Volume 87, No. 9, Year 2013
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Description
Broadly cross-neutralizing (BCN) antibodies are likely to be critical for an effective HIV vaccine. However, the ontogeny of such antibodies and their relationship with autologous viral evolution is unclear. Here, we characterized viral evolution in CAP256, a subtype C-infected individual who developed potent BCN antibodies targeting positions R166 and K169 in the V2 region. CAP256 was superinfected at 3 months postinfection with a virus that was highly sensitive to BCN V2-dependent monoclonal antibodies. The autologous neutralizing response in CAP256 was directed at V1V2, reaching extremely high titers (>1:40,000) against the superinfecting virus at 42 weeks, just 11 weeks prior to the development of the BCN response targeting the same region. Recombination between the primary and superinfecting viruses, especially in V2 and gp41, resulted in two distinct lineages by 4 years postinfection. Although neutralization of some CAP256 clones by plasma from as much as 2 years earlier suggested incomplete viral escape, nonetheless titers against later clones were reduced at least 40-fold to less than 1:1,000. Escape mutations were identified in each lineage, either at R166 or at K169, suggesting that strain-specific and BCN antibodies targeted overlapping epitopes. Furthermore, the early dependence of CAP256 neutralizing antibodies on the N160 glycan decreased with the onset of neutralization breadth, indicating a change in specificity. These data suggest rapid maturation, within 11 weeks, of CAP256 strain-specific antibodies to acquire breadth, with implications for the vaccine elicitation of BCN V2-dependent antibodies. Overall these studies demonstrate that ongoing viral escape is possible, even from BCN antibodies. © 2013, American Society for Microbiology.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3624332/bin/supp_87_9_4882__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3624332/bin/JVI.03424-12_zjv999097526so1.pdf
Authors & Co-Authors
Moore, Penny L.
South Africa, Johannesburg
National Institute for Communicable Diseases
South Africa, Johannesburg
University of the Witwatersrand
Sheward, Daniel J.
South Africa, Johannesburg
National Health Laboratory Service
Nonyane, Molati
South Africa, Johannesburg
National Institute for Communicable Diseases
Ranchobe, Nthabeleng
South Africa, Johannesburg
National Institute for Communicable Diseases
Hermanus, Tandile
South Africa, Johannesburg
National Institute for Communicable Diseases
Gray, Elin Solomonovna
South Africa, Johannesburg
National Institute for Communicable Diseases
Australia, Perth
Edith Cowan University
Abdool Karim, Salim S.
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Williamson, Carolyn
South Africa, Johannesburg
National Health Laboratory Service
Morris, Lynn
South Africa, Johannesburg
National Institute for Communicable Diseases
South Africa, Johannesburg
University of the Witwatersrand
Statistics
Citations: 72
Authors: 9
Affiliations: 5
Identifiers
Doi:
10.1128/JVI.03424-12
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Infectious Diseases