15th International AIDS Conference Bangkok, Thailand — July 11-July 16, 2004

Int Conf AIDS. 2004 Jul 11-16;15:Abstract No. LbOrA05

B Barugahare¹, N Jones², C Baker², S Mutalya¹, M Okello¹, M Eggena³, C Kityo¹, P Mugyenyi¹, H Cao^2
1Joint Clinical Research Centre, Kampala, Uganda; ²California Department of Health Services, Richmond, United States; ³University of California, San Francisco, San Francisco, United States

BACKGROUND: HIV-specific T cell responses are associated with viral control and T cell based-vaccines are currently a primary focus of AIDS vaccine designs. Uganda is one country in which the HIV epidemic has spread rapidly and where at least 3 clades of endemic HIV strains co-exist. The design of a vaccine to induce effective immune responses in regions where multiple HIV subtypes are endemic may be complex. A better understanding of T cell immunity in Uganda may guide future vaccine designs and testing in this population.

METHOD: HIV-seropositive Ugandan adult volunteers were recruited at the Joint Clinical Research Centre in Kampala, Uganda. HIV-specific T cell responses were measured by IFN-γ ELISPOT using consensus clade A and D Gag, Env and Nef peptides. Correlation with clinical parameters including viral load and CD4 cell count were done and statistical significance was defined as p>0.05. HIV subtyping was done by PCR amplification and sequencing of the Gag and Nef regions.

RESULTS: 101 out of 121 volunteers demonstrated HIV-specific responses against clade A or D antigens. 41% and 39% of the infecting strains were clade A and D, respectively. Clade A Gag elicited the highest frequency and magnitude of response (56% and mean 641 SFC/million). High concordance of cross-clade responses were observed between clade A and D for Gag (52% cross-recognition, R2=0.149, P<0.01), Env (45%, R2=0.618, P<0.01) and Nef (45%, R2=0.521, P<0.01). Flow cytometry assays confirmed that responses were CD8-mediated.

CONCLUSION: HIV-specific CD8+ responses in HIV+ Ugandans are easily detected using the ELISPOT assay and high levels of cross-clade recognition even in the highly variable ENV regions are observed. In this cohort, the circulating HIV strains are of subtypes A or D with few recombinant strains identified. The level of cross-clade responses in this population is encouraging for vaccine development for regions where multiple HIV subtypes are endemic.

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LbOrA05

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