Carriers of certain human leukocyte antigen class I alleles show favorable prognosis of human immunodeficiency virus type 1 (HIV-1) infection, presumably due to effective CD8؉ cytotoxic T-lymphocyte responses, but close relationships between class I variants mediating such responses to natural and to vaccine HIV-1 antigen have not been established. During 6 to 30 months of administration and follow-up in trials of ALVAC-HIV recombinant canarypox vaccines, cells from 42% of 291 HIV-1-negative vaccinated subjects typed at class I loci responded to an HIV-1 protein in a lytic bulk CD8؉ cytotoxic T-lymphocyte assay. By 2 weeks after the second dose, higher proportions of vaccinees carrying one of two alleles consistently associated with slower progression of natural HIV-1 infection reacted at least once: B72ء carriers reacted to Gag (64%; odds ratio [OR] ؍ 10.3, P ؍ 0.001) and Env (36%; OR ؍ 4.6, P ؍ 0.04), and B75ء carriers reacted to Env (44%; OR ؍ 6.6, P < 0.05). By 2 weeks after the third or fourth dose, B72ء carriers had responded (two or more reactions) to Gag (33%; OR ؍ 4.4, P < 0.05) and B75ء carriers had responded to both Gag (39%; OR ؍ 5.3, P ؍ 0.013) and Env (39%; OR ؍ 9.5, P ؍ 0.002). Homozygosity at class I loci, although conferring an unfavorable prognosis following natural infection, showed no such disadvantage for vaccine response. Individual class I alleles have not previously demonstrated such clear and consistent relationship with both the clinical course of an infection and cellular immunity to a vaccine against the infectious agent. This proof of principle that class I an alleles modulate both processes has implications for development of HIV-1 and presumably other vaccines.
Further evaluation of workplace exposures or independent investigations of similar occupational groups may clarify the interpretation of associations observed in this study.
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