CYTOTOXIC T-LYMPHOCYTE CROSS-REACTIVITY AMONG DIFFERENT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 CLADES - IMPLICATIONS FOR VACCINE DEVELOPMENT

Despite recent advances in antiviral therapy for human immunodeficienc y virus (HIV) infection, successful global intervention will require a n effective vaccine, Expanding evidence suggests that cytotoxic T-lymp hocyte (CTL) responses will be an important component of such a vaccin e, The varying geographic distribution of HIV type 1 (HIV-1) clades, w ith the relative absence of clade B HIV-1 outside the developed world, is considered a major obstacle to the development of a single efficac ious vaccine, An understanding of cross-reactive CTL responses between different HIV-1 clades is crucial in the design of a vaccine which wi ll be broadly immunogenic, In this study, we examined the ability of H IV-1 Gag-, reverse transcriptase-, and Env-specific CTL clones isolate d from individuals infected in the United States to recognize non-B cl ade viral sequences and found that all were cross-reactive with the ma jority of non-B clade viral sequences tested. We next studied HIV-1-sp ecific CTL responses in African individuals infected with clade A, C, or G virus and evaluated cross-recognition of clade B virus, Of 14 per sons evaluated, all demonstrated cross-reactivity with the U.S. clade B viral constructs, We conclude that significant CTL cross-reactivity exists between clade B and non-B epitopes, suggesting that CTL cross-r ecognition among HIV-1 clades is more widespread than anticipated and that a vaccine based on a single clade may be broadly applicable.