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The most severe human immunodifficiency virus type 1 (HIV-1) epidemic occurs in southern Africa, caused by HIV-1 subtype C (HIV-1C). Cytotoxic T lymphocytes (CTL) were shown to be an important component of the immune response to control 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 population, through the distribution of common HLA class I alleles, might impact dominant CTL responses in the vaccine and in the general population. We studied the distribution of the HLA class I antigen specificities in Botswana, and identified 4 HLA-A, 7 HLA-B, and 5 HLA-C specificities that were observed at high frequencies in the Botswana population: A30, A02, A23, A68, B58, B72, B42, B8, B18, B44, B45, Cw7, Cw2, Cw17, Cw6 and Cw4. To provide molecular characterization of the virus in Botswana we isolated 56 HIV-1 from a cohort of blood donors. All isolated viruses were classified as R5. Near full-length genome sequencing was performed for 27 viral isolates. Samples were screened for the Elispot-based HIV-1 Gag- (n=46), Tat- (n=48), Rev- (n=47), and Nef- (n=45) specific CTL responses. Profiles of cumulative Elispot-based CTL responses combined with diversity and sequence consensus data provide a comprehensive characterization of the identified immunodominant regions across the HIV-1C Gag, Tat, Rev , and Nef .
The results of this study extend the HLA map to a southern African country that has high rates of HIV and also provides a database for the design of an HLA-based HIV vaccine. Results of the study suggest that the construction of a poly-epitope subtype-specific HIV-1 vaccine that includes multiple copies of immunodominant 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.
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