Profile of most frequent HLA class I alleles might be relevant to HLA-based HIV vaccine design in Botswana.
Int Conf AIDS 2000 Jul 9-14; 13:40 (abstract no.. LbPeA7035)
Novitsky V, Flores P, Chingwedere P, Gaolekwe S, Bussman H, Sebetso G, Marlink R, Yunis E, Essex M Harvard School of Public Health, Boston, MA 02115. Fax: +1 617-739-8348, E-mail: vnovi@hsph.harvard.edu.
HIV-1 C is a dominant HIV-1 subtype worldwide responsible for a severe HIV-1 epidemic in Southern Africa. To facilitate the design of the HLA basedanti-HIV vaccine we studied the distribution of the HLA class I alleles in Botswana. At least three reasons establish Botswana as a potential candidate for the vaccine trials: high prevalence of HIV infection; a highly efficient health care system; and central geographical location in Southern Africa.HLA class I genes were studied by molecular HLA typing including SSP and direct sequencing. HLA-A*30, A*02, A*23, A*68, B *58, Cw2, Cw4, Cw6, Cw7, andCw 17 were observed at frequencies of more than 10%. The frequency of HLA-A*30 was 27.3%. HLA-B*58 (17.9%) was the most frequent allele of the HLA-B locus. Other frequent alleles detected in HLA-B locus were B*72(9.6%), B*42 (93%), B*8 (7,4%), B*44 (7.4%), and B*45 (6.4%), Haplotypes HLA-A*30/HLAB*58 (6.7%), A*30/B*42 (6, 1 %), A*30/B*8 (4. 1%), A*30/B*45(3.2%), and A*23/B*58 (2.5%) were the most frequent among two-locus haplotypes, while haplotype HLA-A*30/HLA-B*42/HLA-Cwl7 was found at the highest frequency among three-locus haplotypes of the general Botswana population.The HLA-B*58 allele (and extended haplotypes for HLA-B*58) were associated with increased susceptibility to HIV infection, while HLA-A*68 and HLA-Cw8 were associated with HIV resistance, although differences between groups were not statistically significant, Four HLA-A alleles, six HLA-B alleles, and five HLA-C alleles were observed at high frequencies in the Botswana population: A*30, A*02, A*23, A*68,B*58, B*72, B*42, B*8, B*44, B*45, Cw7, Cw2, Cw 17, Cw6, and Cw4. Our findings suggest that design of an HLAbased HIV vaccine that includes multiple CTL epitopes restricted by identified common HLA class I alleles might target up to 97.5% of the population in Botswana. The results of this study extend the HLA map to a South African country with high rates of HIV and provide a database for the design of HLA-based HIV vaccine.
Keywords: AEGIS, HLA Antigens, AIDS Vaccines, Alleles, HLA-B Antigens, HLA-C Antigens, Haplotypes, Histocompatibility Testing, HIV-1, HIV Infections, Epitopes, Botswana, Africa, Southern, HLA-Cw8, immunology, genetics, AIDS 000709
LbPeA7035
