title: Identification of most frequent HLA class I antigen specificities in Botswana: relevance for HIV vaccine design.
abstract: Since the mid-1990s, southern African countries have been experiencing an expansion of human immunodeficiency virus type 1 (HIV-1) infection caused by HIV-1 subtype C. To facilitate the design of an HLA-based HIV vaccine, we studied the distribution of the HLA class I antigen specificities in Botswana, a southern African country with a high prevalence of HIV infection. Botswana's highly efficient health care system and its central geographical location within southern Africa suggests that it might be an appropriate candidate site for future trials of an HLA-based HIV vaccine. Specificities of HLA class I genes have been investigated in DNA samples obtained from 161 persons of Botswana origin by polymerase chain reaction (PCR) with sequence-specific primers. We 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. HLA-A30, A02, A23, A68, B58, Cw2, Cw4, Cw6, Cw7, and Cw17 were observed at frequencies of more than 10%. The frequency of HLA-A30 was 27.3%. HLA-B58 (17.9%) was the most frequent generic HLA-B type. Other frequent antigen specificities detected for the HLA-B were B72 (9.6%), B42 (9.3%), B8 (7.4%), B18 (7.4%), B44 (7.4%), and B45 (6.4%). Analysis of haplotype frequencies revealed that haplotypes HLA-A30/HLA-B58 (6.7%), A30/B42 (6.1%), A30/B8 (4.1%), A30/B45 (3.2%), and A23/B58 (2.5%) were the most frequent among two-locus haplotypes. The comparison of HIV-positive patients and noninfected controls for HLA class I specificities confirmed the previously described association of A2/A6802 supertype with resistance to HIV. Our study suggested an increased resistance to HIV infection associated with A68 rather than A2. We also found that the generic HLA-B58 type was associated with increased susceptibility to HIV infection. Our findings suggest that the design of an HLA-based HIV vaccine that includes multiple CTL epitopes restricted by identified common HLA class I specificities might target up to 97.5% of the population in Botswana. The results of this study extend the HLA map to a southern African country that has high rates of HIV and also provide a database for the design of an HLA-based HIV vaccine.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: V
authors.initials: V
authors.lastname: Novitsky
authors.forename: P O
authors.initials: PO
authors.lastname: Flores-Villanueva
authors.forename: P
authors.initials: P
authors.lastname: Chigwedere
authors.forename: S
authors.initials: S
authors.lastname: Gaolekwe
authors.forename: H
authors.initials: H
authors.lastname: Bussman
authors.forename: G
authors.initials: G
authors.lastname: Sebetso
authors.forename: R
authors.initials: R
authors.lastname: Marlink
authors.forename: E J
authors.initials: EJ
authors.lastname: Yunis
authors.forename: M
authors.initials: M
authors.lastname: Essex
mesh_terms: D016915:AIDS Vaccines / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D044383:Black People / Q000235:genetics; D001902:Botswana; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000097:blood; D000939:Epitopes / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000276:immunology; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D044465:White People / Q000235:genetics
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D005819:Genetic Markers; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D004247:DNA