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 res ponse to viral infection by recognizing and destroying infected cells. HIV-1 elicits an unusually strong CTL response in infected individual s and clearance of the viremia of acute infection coincides with the d evelopment of HIV-specific CTL. Because HIV-specific CTL may provide p rotection against de novo viral infection, we compared the CTL respons e in seronegative volunteers treated with two vaccination approaches. Seven volunteers were immunized with a live recombinant vaccinia virus expressing the HIV envelope protein gp160(LAI) (HIVAC-le) and boosted with 640 mu g recombinant baculovirus-expressed gp160(LAI) in alum 1- 13 months later. In a second study, three volunteers underwent four su ccessive immunizations with 640 mu g subunit gp160(LAI) in alum at 0, 1, 6, and 12 months. The first vaccination strategy using a live vecto r would be expected to generate gp160-specific CTL, while for the seco nd, using only whole-protein subunit, the generation of specific CTL w ould be unlikely. Predominantly CD8(+) T-cell lines generated from PBM C by nonspecific stimulation with PHA and IL-2 were screened after thr ee to four weeks of culture for cytolytic activity against autologous targets infected with vaccinia vectors encoding env(LAI), RT, gag, and lacZ control. A strong gp160-specific CTL response was detected in tw o vaccinees in the recombinant vaccinia plus subunit boost study. Mode st responses were seen in four of the other five live vector-primed va cciness. No significant gp160-specific CTL were observed in three volu nteers given only subunit rgp160 or in five control subjects.