A Vaccinia-gp160-Based Vaccine But Not a gp160 Protein Vaccine Elicits Anti-gp160 Cytotoxic T Lymphocytes in Some HIV-1 Seronegative Vaccinees.

Perales, Miguel-Angel; Schwartz, David H.; Fabry, Jessica A.; Lieberman, Judy
Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology:
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Summary: 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-le) and boosted with 640 [mu]g recombinant baculo-virus-expressed gp160LAI in alum 1-13 months later. In a second study, three volunteers underwent four successive immunizations with 640 [mu]g subunit gp160LAI in alum at 0, 1, 6, and 12 months. The first vaccination strategy using a live 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 gp160-specific CTL response was detected in two vaccinees 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.

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