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Caprisa (Centre for the Aids programme of research in South Africa)

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Browsing Caprisa (Centre for the Aids programme of research in South Africa) by Subject "Acute HIV-1 infection."

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    High titer HIV-1 V3-specific antibodies with broad reactivity but low neutralizing potency in acute infection and following vaccination.
    (Elsevier, 2008) Davis, Katie L.; Gray, Elin Solomonovna.; Moore, Penelope L.; Decker, Julie M.; Salomon, Aidy.; Montefiori, David Charles.; Graham, Barney S.; Keefer, Michael C.; Pinter, Abraham.; Morris, Lynn.; Hahn, Beatrice H.; Shaw, George M.
    Identifying the earliest neutralizing antibody specificities that are elicited following infection or vaccination by HIV-1 is an important objective of current HIV/AIDS vaccine research. We have shown previously that transplantation of HIV-1 V3 epitopes into an HIV-2 envelope (Env) scaffold provides a sensitive and specific means to detect and quantify HIV-1 V3 epitope specific neutralizing antibodies (Nabs) in human sera. Here, we employ this HIV-2/HIV-1 V3 scaffolding strategy to study the kinetics of development and breadth of V3- specific Nabs in longitudinal sera from individuals acutely infected with clade C or clade B HIV-1 and in human subjects immunized with clade B HIV-1 immunogens. HIV-2/HIV-1 chimeras containing V3 sequences matched to virus type (HIV-2 or HIV-1), subtype (clade B or C), or strain (autologous or heterologous) were used as test reagents. We found that by 3–8 weeks post infection, 12 of 14 clade C subjects had a median IC50 V3-specific Nab titer of 1:700 against chimeric viruses containing a heterologous clade C V3. By 5 months post-infection, all 14 subjects were positive for V3-specific Nabs with median titers of 1:8000 against heterologous clade C V3 and 1:1300 against clade B V3. Two acutely infected clade B patients developed heterologous clade B V3-specific Nabs at titers of 1:300 and 1:1800 by 13 weeks of infection and 1:5000 and 1:11000 by 7 months of infection. Titers were not different against chimeras containing autologous clade B V3 sequences. Each of 10 uninfected normal human volunteers who were immunized with clade B HIV-1 Env immunogens, but none of five sham immunized control subjects, developed V3-specific Nabs titers as high as 1:3000 (median 1:1300; range 1:700–1:3000). None of the HIV- 1 infected or vaccinated subjects had antibodies that neutralized primary HIV-1 virus strains. These results indicate that high-titer, broadly reactive V3-specific antibodies are among the first to be elicited during acute and early HIV-1 infection and following vaccination but these antibodies lack neutralizing potency against primary HIV-1 viruses, which effectively shield V3 from antibody binding to the functional Env trimer.
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    Relationship between levels of inflammatory cytokines in the genital tract and CD4+ cell counts in women with acute HIV-1 infection.
    (The Infectious Diseases Society of America., 2008) Bebell, Lisa M.; Passmore, Jo-Ann Shelley.; Williamson, Carolyn.; Mlisana, Koleka Patience.; Iriogbe, Itua.; van Loggerenberg, Francois.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.
    Inflammatory responses at mucosal surfaces after human immunodeficiency virus type 1 (HIV-1) transmission may influence disease outcome.We evaluated levels of interleukin (IL)–1B , IL-6, tumor necrosis factor– a, IL-8, IL-10, and IL-12 in genital tract and plasma specimens from 44 women with acute HIV infection and 29 HIV-negative control women (13 of whom were women in the acute HIV infection cohort who had preinfection samples available for analysis). Women with acute HIV infection had significantly elevated levels of IL-6, IL-10, and IL-12 in genital tract specimens and elevated levels of IL-1B , IL-8, and IL-10 in plasma specimens, compared with HIV-negative control women. Levels of IL-1B , IL-6, and IL-8 in cervicovaginal specimens from women with acute HIV infection showed a significant inverse correlation with systemic CD4 + cell counts, suggesting that mucosal inflammation is associated with low CD4 + cell counts during acute HIV infection.