Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers

Objective: To determine the ability of live attenuated canarypox virus expr essing HIV antigens to induce CD8+ cytotoxic T-cell responses and to prime for neutralizing antibody responses to boosting with purified recombinant g p120 subunit vaccine. Design: A prospective, double-blind, randomized, immunogenicity and safety study was conducted in healthy adults at low risk for acquiring HIV infecti on and who were seronegative for HIV. Methods: CD8+ cytotoxic T-cells directed against Env or Gag expressing targ et cells were measured after live recombinant canarypox-HIV-1 vaccine primi ng (vaccine given at days 0, 7, 14 and 21). Neutralizing antibodies were me asured after subunit boosting (vaccine given at days 28 and 84). Results: CD8+ CTL were induced in 64% of volunteers by the live recombinant canarypox-HIV-1 vaccine. All volunteers who received two doses of subunit vaccine after live recombinant canarypox priming developed neutralizing ant ibodies directed against laboratory strains of HIV-1 and seven out of eight volunteers tested developed neutralizing antibodies to the primary isolate , BZ167, but to none of eight other primary isolates. Unprimed controls had low or absent neutralizing antibodies after two doses of subunit vaccine. Conclusions: The live canarypox vector was safe, stimulated cytotoxic T-cel ls and primed for a vigorous neutralizing antibody response upon boosting w ith subunit gp120 vaccine. This vaccine combination should be evaluated fur ther for inducing protection against HIV infection. (C) 1998 Lippincott Wil liams & Wilkins.