Browsing by Author "Bandawe, Gama P."

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CAPRISA 004 tenofovir microbicide trial: no impact of tenofovir gel on the HIV transmission bottleneck.
(Oxford University Press., 2011) Valley-Omar, Ziyaad.; Sibeko, Sengeziwe.; Anderson, Jeffrey A.; Goodier, Sarah A.; Werner, Lise.; Arney, Leslie.; Naranbhai, Vivek.; Treurnicht, Florette K.; Abrahams, Melissa-Rose.; Bandawe, Gama P.; Swanstrom, Ronald.; Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.; Williamson, Carolyn.
Alterations of the genital mucosal barrier may influence the number of viruses transmitted from a human immunodeficiency virus–infected source host to the newly infected individual. We used heteroduplex tracking assay and single-genome sequencing to investigate the effect of a tenofovir-based microbicide gel on the transmission bottleneck in women who seroconverted during the CAPRISA 004 microbicide trial. Seventy-seven percent (17 of 22; 95% confidence interval [CI], 56%–90%) of women in the tenofovir gel arm were infected with a single virus compared with 92% (13 of 14; 95% CI, 67%–>99%) in the placebo arm (P = .37). Tenofovir gel had no discernable impact on the transmission bottleneck.
Differences in HIV-1 neutralization breadth in two geographically distinct cohorts in Africa.
(Oxford University Press., 2015) Bandawe, Gama P.; Moore, Penelope L.; Werner, Lise.; Gray, Elin Solomonovna.; Sheward, Daniel J.; Madiga, Maphuti C.; Nofemela, Andile.; Thebus, Ruwayhida.; Marais, Jinny C.; Maboko, Leonard.; Abdool Karim, Salim Safurdeen.; Hoelscher, Michael.; Morris, Lynn.; Williamson, Carolyn.
Abstract available in pdf.
Features of recently transmitted HIV-1 clade C viruses that impact antibody recognition : implications for active and passive immunization.
(Public Library of Science., 2016) Rademeyer, Cecilia.; Korber, Bette T. M.; Seaman, Michael S.; Giorgi, Elena E.; Thebus, Ruwayhida.; Robles, Alexander.; Sheward, Daniel J.; Wagh, Kshitij.; Garrity, Jetta.; Carey, Brittany R.; Gao, Hongmei.; Greene, Kelli M.; Tang, Haili.; Bandawe, Gama P.; Marais, Jinny C.; Diphoko, Thabo E.; Hraber, Peter.; Tumba, Nancy Lola.; Moore, Penelope L.; Gray, Glenda Elizabeth.; Kublin, James.; McElrath, Margaret Juliana.; Vermeulen, Marion.; Middelkoop, Keren.; Bekker, Linda-Gail.; Hoelscher, Michael.; Maboko, Leonard.; Makhema, Joseph.; Robb, Merlin L.; Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.; Kim, Jerome H.; Hahn, Beatrice H.; Gao, Feng.; Swanstrom, Ronald.; Morris, Lynn.; Montefiori, David Charles.; Williamson, Carolyn.
Abstract available in PDF file.
Limited Neutralizing Antibody Specificities Drive Neutralization Escape in Early HIV-1 Subtype C Infection.
(Plos, 2009) Moore, Penelope L.; Ranchobe, Nthabeleng.; Lambson, Bronwen Elizabeth.; Gray, Elin Solomonovna.; Cave, Eleanor.; Abrahams, Melissa-Rose.; Bandawe, Gama P.; Mlisana, Koleka Patience.; Abdool Karim, Salim Safurdeen.; Williamson, Carolyn.; Morris, Lynn.
We previously showed that HIV-1 subtype C viruses elicit potent but highly type-specific neutralizing antibodies (nAb) within the first year of infection. In order to determine the specificity and evolution of these autologous nAbs, we examined neutralization escape in four individuals whose responses against the earliest envelope differed in magnitude and potency. Neutralization escape occurred in all participants, with later viruses showing decreased sensitivity to contemporaneous sera, although they retained sensitivity to new nAb responses. Early nAb responses were very restricted, occurring sequentially and targeting only two regions of the envelope. In V1V2, limited amino acid changes often involving indels or glycans, mediated partial or complete escape, with nAbs targeting the V1V2 region directly in 2 cases. The alpha-2 helix of C3 was also a nAb target, with neutralization escape associated with changes to positively charged residues. In one individual, relatively high titers of anti-C3 nAbs were required to drive genetic escape, taking up to 7 weeks for the resistant variant to predominate. Thereafter titers waned but were still measurable. Development of this single anti-C3 nAb specificity was associated with a 7-fold drop in HIV-1 viral load and a 4-fold rebound as the escape mutation emerged. Overall, our data suggest the development of a very limited number of neutralizing antibody specificities during the early stages of HIV-1 subtype C infection, with temporal fluctuations in specificities as escape occurs. While the mechanism of neutralization escape appears to vary between individuals, the involvement of limited regions suggests there might be common vulnerabilities in the HIV-1 subtype C transmitted envelope.