Prevention of encephalomyocarditis virus-induced diabetes by live recombinant Mycobacterium bovis bacillus Calmette-Guerin in susceptible mice

The D variant of encephalomyocarditis (EMC-D) virus causes diabetes in susc eptible mice by direct cytolysis of pancreatic beta-cells. cDNA covering th e major outer capsid protein (VP1) of the EMC-D virus was cloned into Mycob acterium bovis bacillus Calmette-Guerin (BCG), None of the SJL/J mice immun ized with live recombinant BCG-VP1 (rBCG-VP1) became diabetic when challeng ed with the highly diabetogenic EMC-D virus, but the control mice inoculate d with normal BCG developed diabetes during the same challenge. VP1-specifi c antibodies (including neutralizing antibodies) were markedly increased ov er time and reached the maximum titer at week 10 after a single immunizatio n. The plateau of the titer lasted longer than 4 weeks. Mice and guinea pig s immunized with live rBCG-VP1 showed strong delayed-type hypersensitivity to the VP1 of the EMC-D virus, The preventive immunity still worked effecti vely 10 months after the primary immunization. At that; time, the VP1-speci fic antibody was almost undetectable in the bloodstream, but a large number of VP1-specific lymphocytes was found in the spleen of the immunized mice, Our results show that live rBCG-VP1 elicits effective humoral and long-las ting cellular immune responses against EMC-D virus infection that results i n the prevention of virus-induced diabetes in susceptible mice.