Identification of human immunodeficiency virus type 1 subtype C Gag-, Tat-, Rev-, and Nef-specific Elispot-based cytotoxic T-lymphocyte responses forAIDS vaccine design

The most severe human immunodeficiency virus type 1 (HIV-1) epidemic is occ urring in southern Africa. It is caused by HIV-1 subtype C (HIV-1C). In thi s study we present the identification and analysis of cumulative cytotoxic T-lymphocyte (CTL) responses in the southern African country of Botswana. C TLs were shown to be an important component of the immune response to contr ol HIV-1 infection. The definition of optimal and dominant epitopes across the HIV-1C genome that are targeted by CTL is critical for vaccine design. The characteristics of the predominant virus that causes the HIV-1 epidemic in a certain geographic area and also the genetic background of the popula tion, through the distribution of common HLA class I alleles, might impact dominant CTL responses in the vaccinee and in the general population. The e nzyme-linked immunospot (Elispot) gamma interferon assay has recently been shown to be a reliable tool to map optimal CTL epitopes, correlating well w ith other methods, such as intracellular staining, tetramer staining, and t he classical chromium release assay. Using Elispot with overlapping synthet ic peptides across Gag, Tat, Rev, and Nef, we analyzed HIV-1C-specific CTL responses of HIV-1-infected blood donors. Profiles of cumulative Elispot-ba sed CTL responses combined with diversity and sequence consensus data provi de an additional characterization of immunodominant regions across the HIV- IC genome. Results of the study suggest that the construction of a poly-epi tope subtype-specific HIV-1 vaccine that includes multiple copies of immuno dominant CTL epitopes across the viral genome, derived from predominant HIV -1 viruses, might be a logical approach to the design of a vaccine against AIDS.