RECOMBINANT MYCOBACTERIUM-BOVIS BCG PRODUCING THE N-TERMINAL HALF OF SIVMAC251 ENV ANTIGEN INDUCES NEUTRALIZING ANTIBODIES AND CYTOTOXIC T-LYMPHOCYTE RESPONSES IN MICE AND GUINEA-PIGS

Recombinant Mycobacterium bovis bacillus Calmette-Guerin (rBCG) repres ents a good candidate for the development of vaccines against AIDS, Se veral HIV or SIV genes including nef, gag, and env have already been e xpressed by rBCG strains and shown to induce strong humoral and cellul ar immune responses in experimental animals, Because a broad immune re sponse directed to multiple HIV/SIV antigens is highly desirable in or der to develop effective vaccines, me have also investigated the immun e response induced by an rBCG strain expressing a large N-terminal por tion of the SIVmac251 Env gp110-encoding gene, The rBCG(SIVmac251Env) strain obtained was able to induce strong CTL responses in mice as wel l as humoral immune responses in mice and guinea pigs immunized by par enteral routes, The anti-gp110 IgGs produced mere able to neutralize i n vitro growth of virulent SIVmac251 field isolates, Moreover, guinea pigs immunized by the oral route produced significant levels of anti-g p110 IgAs in the feces, demonstrating that rBCG is able to induce loca l humoral immunity in the intestinal mucosa. These data provide furthe r evidence of the utility of BCG as a candidate vaccine vector against AIDS.