A vaccinia-gp160-based vaccine but not a gp160 protein vaccine elicits anti-gp160 cytotoxic T lymphocytes in some HIV-1 seronegative vaccinees.

Cytotoxic T lymphocytes (CTL) play an important role in the immune response to viral infection by recognizing and destroying infected cells. HIV-1 elicits an unusually strong CTL response in infected individuals and clearance of the viremia of acute infection coincides with the development of HIV-specific CTL. Because HIV-specific CTL may provide protection against de novo viral infection, we compared the CTL response in seronegative volunteers treated with two vaccination approaches. Seven volunteers were immunized with a live recombinant vaccinia virus expressing the HIV envelope protein gp160LAI (HIVAC-1e) and boosted with 640 micrograms recombinant baculovirus-expressed gp160LAI in alum 1-13 months later. In a second study, three volunteers underwent four successive immunizations with 640 micrograms subunit gp160LAI in alum at 0, 1, 6, and 12 months. The first vaccination strategy using a liver vector would be expected to generate gp160-specific CTL, while for the second, using only whole-protein subunit, the generation of specific CTL would be unlikely. Predominantly CD8+ T-cell lines generated from PBMC by nonspecific stimulation with PHA and IL-2 were screened after three to four weeks of culture for cytolytic activity against autologous targets infected with vaccinia vectors encoding envLAI, RT, gag, and lacZ control. A strong gp 160-specific CTL response was detected in two vaccines in the recombinant vaccinia plus subunit boost study. Modest responses were seen in four of the other five live vector-primed vaccinees. No significant gp160-specific CTL were observed in three volunteers given only subunit rgp160 or in five control subjects.