The kinetics of specific immune responses in rhesus monkeys inoculated with live recombinant BCG expressing SIV Gag, Pol, Env, and Nef proteins

Development of an effective preventive or therapeutic vaccine against HIV-1 is an important goal in the fight against AIDS. Effective virus clearance and inhibition of spread to target organs depends principally on the cellul ar immune response. Therefore, a vaccine against HIV-1 should elicit virus- specific cytotoxic lymphocyte (CTL) responses to eliminate the virus during the cell-associated stages of its life cycle. The vaccine should also be c apable of inducing Immunity at the mucosal surfaces, the primary route of t ransmission. Recombinant Bacille Calmette-Guerin (BCG) expressing viral pro teins offers an excellent: candidate Vaccine in view of its safety and abil ity to persist intracellularly, resulting in the induction of long-lasting immunity and stimulation of the cellular immune response. BCG can be admini stered orally to induce HIV-specific immunity at the mucosal surfaces. The immunogenicity of four recombinant BCG constructs expressing simian immunod eficiency virus (SIV) Gag, Pol, Env, and Nef proteins was tested in rhesus macaques. A single simultaneous inoculation of all four recombinants elicit ed SIV-specific IgA and IgG antibody, and cellular immune responses, includ ing CTL and helper T cell proliferation. Our results demonstrate that BCG r ecombinant vectors can induce concomitant humoral and cellular immune respo nses to the major proteins of SIV. (C) 2000 Academic Press.