Prevention of encephalomyocarditis virus-induced diabetes by live recombinant Mycobacterium bovis bacillus Calmette-Guérin in susceptible mice.
The D variant of encephalomyocarditis (EMC-D) virus causes diabetes in susceptible mice by direct cytolysis of pancreatic beta-cells. cDNA covering the major outer capsid protein (VP1) of the EMC-D virus was cloned into Mycobacterium bovis bacillus Calmette-Guerin (BCG). None of the SJL/J mice immunized with live recombinant BCG-VP1 (rBCG-VP1) became diabetic when challenged with the highly diabetogenic EMC-D virus, but the control mice inoculated with normal BCG developed diabetes during the same challenge. VP1-specific antibodies (including neutralizing antibodies) were markedly increased over time and reached the maximum titer at week 10 after a single immunization. The plateau of the titer lasted longer than 4 weeks. Mice and guinea pigs immunized with live rBCG-VP1 showed strong delayed-type hypersensitivity to the VP1 of the EMC-D virus. The preventive immunity still worked effectively 10 months after the primary immunization. At that time, the VP1-specific 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-lasting cellular immune responses against EMC-D virus infection that results in the prevention of virus-induced diabetes in susceptible mice.
Choi
B K
BK
Department of Microbiology, Hannam University, Taejon City, South Korea.
Cho
S H
SH
Bai
G H
GH
Kim
S J
SJ
Hyun
B H
BH
Choe
Y K
YK
Bae
Y S
YS
D000818:Animals; D001500:BCG Vaccine / Q000627:therapeutic use*; D001483:Base Sequence; D002213:Capsid / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins; D018188:Cardiovirus Infections / Q000150:complications*; D003001:Cloning, Molecular; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control* / Q000821:virology*; D004686:Encephalomyocarditis virus / Q000235:genetics / Q000276:immunology; D016679:Genome, Viral; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000627:therapeutic use*
D001500:BCG Vaccine; D036022:Capsid Proteins; D011994:Recombinant Proteins; C096256:VP1 protein, encephalomyocarditis virus; D014614:Vaccines, Synthetic