ENHANCED T-CELL IMMUNOGENICITY AND PROTECTIVE EFFICACY OF A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VACCINE REGIMEN CONSISTING OF CONSECUTIVE PRIMING WITH DNA AND BOOSTING WITH RECOMBINANT FOWLPOX VIRUS

The induction of human immunodeficiency virus (HIV)-specific T-cell re sponses is widely seen as critical to the development of effective imm unity to HIV type 1 (HIV-1). Plasmid DNA and recombinant fowlpox virus (rFPV) vaccines are among the most promising safe HIV-1 vaccine candi dates. However, the immunity induced by either vaccine alone may be in sufficient to provide durable protection against HIV-1 infection. We e valuated a consecutive immunization strategy involving priming with DN A and boosting with rFPV vaccines encoding common HIV-1 antigens. In m ice, this approach induced greater HIV-l-specific immunity than either vector alone and protected mice from challenge with a recombinant vac cinia virus expressing HIV-1 antigens. In macaques, a dramatic boostin g effect on DNA vaccine-primed HIV-l-specific helper and cytotoxic T-l ymphocyte responses, but a decline in HIV-1 antibody titers, was obser ved following rFPV immunization. The vaccine regimen protected macaque s from an intravenous HIV-1 challenge, with the resistance most likely mediated by T-cell responses. These studies suggest a safe strategy f or the enhanced generation of T-cell-mediated protective immunity to H IV-1.