GENETIC-CONTROL OF ANTIBODY-RESPONSES INDUCED BY RECOMBINANT MYCOBACTERIUM-BOVIS BCG EXPRESSING A FOREIGN ANTIGEN

Recombinant Mycobacterium bovis BCG expressing foreign antigens repres ents a promising candidate for the development of future vaccines and was shown in several experimental models to induce protective immunity against bacterial or parasitic infections. Innate resistance to BCG i nfection is under genetic control and could modify the immune response s induced against an antigen delivered by such engineered microorganis ms, To investigate this question, we analyzed the immune responses of various inbred strains of mice to recombinant BCG expressing beta-gala ctosidase, These experiments demonstrated that BALB/c mice developed s trong antibody responses against BCG expressing beta-galactosidase und er the control of two different promoters, In contrast, C57BL/6, C3H, and CBA mice produced high anti-beta-galactosidase antibody titers onl y when immunized with recombinant BCG expressing beta-galactosidase un der the control of the pblaF promoter, which induced the production o f high levels of this antigen. This difference in mouse responsiveness to recombinant BCG was not due to innate resistance to BCG infection, since similar immune responses were induced in Ity' and Ity(s) congen ic strains of mice. In contrast, the analysis of anti-beta-galactosida se antibody responses of H-2 congenic mice in two different genetic ba ckgrounds demonstrated that H-2 genes are involved in the immune respo nsiveness to beta-galactosidase delivered by recombinant BCG, Together , these results demonstrate that immune responses to an antigen delive red by recombinant BCG are under complex genetic influences which coul d play a crucial role in the efficiency of future recombinant BCG vacc ines.