Browsing by Author "Choge, Isaac Ang'Ang'A."

Now showing 1 - 3 of 3

The C3-V4 region is a major target of autologous neutralizing antibodies in human immunodeficiency virus type 1 subtype C Infection.
(American Society for Microbiology., 2008) Moore, Penelope L.; Gray, Elin Solomonovna.; Choge, Isaac Ang'Ang'A.; Ranchobe, Nthabeleng.; Mlisana, Koleka Patience.; Abdool Karim, Salim Safurdeen.; Williamson, Carolyn.; Morris, Lynn.
The early autologous neutralizing antibody response in human immunodeficiency virus type 1 (HIV-1) subtype C infections is often characterized by high titers, but the response is type specific with little to no cross-neutralizing activity. The specificities of these early neutralizing antibodies are not known; however, the type specificity suggests that they may target the variable regions of the envelope. Here, we show that cross-reactive anti-V3 antibodies developed within 3 to 12 weeks in six individuals but did not mediate autologous neutralization. Using a series of chimeric viruses, we found that antibodies directed at the V1V2, V4, and V5 regions contributed to autologous neutralization in some individuals, with V1V2 playing a more substantial role. However, these antibodies did not account for the total neutralizing capacity of these sera against the early autologous virus. Antibodies directed against the C3-V4 region were involved in autologous neutralization in all four sera studied. In two sera, transfer of the C3-V4 region rendered the chimera as sensitive to antibody neutralization as the parental virus. Although the C3 region, which contains the highly variable α2-helix was not a direct target in most cases, it contributed to the formation of neutralization epitopes as substitution of this region resulted in neutralization resistance. These data suggest that the C3 and V4 regions combine to form important structural motifs and that epitopes in this region are major targets of the early autologous neutralizing response in HIV-1 subtype C infection.
Mannose-rich glycosylation patterns on HIV-1 subtype C gp120 and sensitivity to the lectins, Griffithsin, Cyanovirin-N and Scytovirin.
(Elsevier., 2010) Alexandre, Kabamba B.; Gray, Elin Solomonovna.; Lambson, Bronwen Elizabeth.; Moore, Penelope L.; Choge, Isaac Ang'Ang'A.; Mlisana, Koleka Patience.; Abdool Karim, Salim Safurdeen.; McMahon, James.; O'Keefe, Barry.; Chikwamba, Rachel.; Morris, Lynn.
Griffithsin (GRFT), Cyanovirin-N (CV-N) and Scytovirin (SVN) are lectins that inhibit HIV-1 infection by binding to multiple mannose-rich glycans on the HIV-1 envelope glycoproteins (Env). Here we show that these lectins neutralize subtype C primary virus isolates in addition to Env-pseudotyped viruses obtained from plasma and cervical vaginal lavages. Among 15 subtype C pseudoviruses, the median IC50 values were 0.4, 1.8 and 20.1 nM for GRFT, CV-N and SVN, respectively, similar to what was found for subtype B and A. Analysis of Env sequences suggested that concomitant lack of glycans at positions 234 and 295 resulted in natural resistance to these compounds, which was confirmed by site-directed mutagenesis. Furthermore, the binding sites for these lectins overlapped that of the 2G12 monoclonal antibody epitope, which is generally absent on subtype C Env. This data support further research on these lectins as potential microbicides in the context of HIV-1 subtype C infection.
Neutralizing antibody responses in acute human immunodeficiency virus type 1 subtype C infection.
(American society for Microbiology., 2007-03-22) Moore, Penelope L.; Decker, Julie M.; Bibollet-Ruche, F.; Li, Hui.; Leseka, N.; Gray, Elin Solomonovna.; Choge, Isaac Ang'Ang'A.; Abdool Karim, Salim Safurdeen.; Treurnicht, Florette K.; Mlisana, Koleka Patience.; Shaw, George M.; Williamson, Carolyn.; Morris, Lynn.
The study of the evolution and specificities of neutralizing antibodies during the course of human immunodeficiency virus type 1 (HIV-1) infection may be important in the discovery of possible targets for vaccine design. In this study, we assessed the autologous and heterologous neutralization responses of 14 HIV-1 subtype C-infected individuals, using envelope clones obtained within the first 2 months postinfection. Our data show that potent but relatively strain-specific neutralizing antibodies develop within 3 to 12 months of HIV-1 infection. The magnitude of this response was associated with shorter V1-to-V5 envelope lengths and fewer glycosylation sites, particularly in the V1-V2 region. Anti-MPER antibodies were detected in 4 of 14 individuals within a year of infection, while antibodies to CD4-induced (CD4i) epitopes developed to high titers in 12 participants, in most cases before the development of autologous neutralizing antibodies. However, neither anti-MPER nor anti-CD4i antibody specificity conferred neutralization breadth. These data provide insights into the kinetics, potency, breadth, and epitope specificity of neutralizing antibody responses in acute HIV-1 subtype C infection.