INDUCTION OF CELL-MEDIATED IMMUNE-RESPONSES TO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GAG PROTEIN BY USING LISTERIA-MONOCYTOGENES AS A LIVE VACCINE VECTOR

Cytolytic T cells, acting through cytokines or by direct lysis of infe cted target cells, have been shown to play a significant role in the c ontrol of viral infections and may be responsible for the prolonged as ymptomatic phase following infection by HIV. Accordingly, methods that can generate strong cell-mediated immune responses may be useful in t he development of prophylactic and therapeutic vaccines against HIV. L isteria monocytogenes is a Gram-positive intracellular microorganism t hat elicits strong cell-mediated immune responses against its own secr eted proteins following infection. In this study we have modified the chromosome of L. monocytogenes so that it stably expresses and secrete s the p55 HIV gag gene product and examined the cell-mediated immune r esponse of BALB/c mice to infection with this recombinant organism. In fected animals were found to mount a specific, strong, long-lasting CD 8(+) cytolytic T cell response against a predominant epitope contained within the p24 fragment of the HIV Gag protein. This epitope previous ly has been shown to be recognized by CTLs obtained from some HIV-infe cted humans. Our results suggest that chromosomally modified strains o f L. monocytogenes may provide valuable vaccine vectors for use agains t HIV.