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

Int Conf AIDS. 2004 Jul 11-16;15:Abstract No. LbOrA07

A Dieng Sarr¹, A Shea², N Jones², A Gueye-Ndiaye³, S MBoup³, P Kanki¹, H Cao^2
1Harvard School of Public Health, Boston, United States; ²California Department of Health Services, Richmond, United States; ³Universite Cheikh Anta Diop, Dakar, Senegal

BACKGROUND: HIV-2 infection is associated with lower viral replication, transmission rate and progression to AIDS compared to HIV-1. In previous prospective, epidemiologic studies, HIV-2 infection provided protection against subsequent HIV-1 infection in a cohort of commercial sex worker in Dakar, Senegal. To date, the mechanism for protective effect conferred by HIV-2 infection remains unresolved.

METHOD: A total of 94 participants were randomly selected from a prospective cohort of registered female commercial sex workers in Dakar, Senegal. PBMCs from 27 HIV-2 positive, 45 HIV-1-positive and 22 HIV seronegative individuals were evaluated for HIV-specific T cell response. IFN-γ ELISPOT assays was performed using HIV-2 (Gag, Env and Nef) and HIV-1 clade A (Gag) synthetic overlapping peptides. Results are considered positive if twice above background, >50 SFU/million PBMC and confirmed by subsequent assays. Reported responses are CD8-mediated as demonstrated by flow cytometry or CD8 enrichment confirmation.

RESULTS: 23 out of 27 HIV-2-seropositive individuals demonstrated HIV-2-specific T cells responses to Gag, Env or Nef antigens with 15 individuals demonstrating responses to >2 epitopes. Of the 20 individuals who demonstrated Gag-specific activities, 7 had cross-reactive responses to HIV-1 Gag. High representation of immunogenic regions in HIV-2 p24 was observed. The magnitude of the T cell responses was comparable between HIV-1 and HIV-2 positive individuals (p>0.05) despite significant clinical differences HIV viral load. None of the HIV seronegative volunteers had demonstrable HIV-specific responses.

CONCLUSION: HIV-2 infection induces broadly reactive CD8+ T cell responses that consistently target immunodominant regions primarily in Gag p24. HIV-1 cross-recognition was also observed in a subgroup of individuals. The breadth and magnitude of responses in the HIV-2 seropositive cohort with relatively preserved immune status (median CD4 = 623) support the importance of antiviral T cell responses in HIV immunoprotection.

040711
LbOrA07

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