99th General Meeting of the American Society for Microbiology
May 30 - June 3, 1999
Chicago, Illinois
Embargoed until date of presentation.
For more information on any presentation at the 99th General Meeting contact Jim
Sliwa, ASM Communications at [email protected].
Prevention of Type 1 Diabetes by a Single Immunization with a Newly Cloned BCG
(Session 291, Paper E100)
Yong-Soo Bae
Hannam University
82-42-629-7528
[email protected]
Diabetes was prevented by a single vaccination with a newly cloned bovine mycobacterium (BCG). Dr. Yong-Soo Bae and his colleagues cloned a BCG strain expressing a surface antigen of a picornavirus. They have shown that the BCG clone protects the immunized mice from the virus-induced diabetes when challenged with a highly diabetogenic encephalomyocarditis (EMC) virus. Their results strongly suggest that the recombinant BCG system can be applicable for the development of preventive vaccines against virus-induced diabetes and other infectious diseases in humans.
Dr. Bae, an associate professor at Hannam University, Korea, has been working this project for the last 3 years with his graduate students and collaborators of Korea Institute of Tuberculosis with a Grant from Korea Ministry of Science and Technology. Most of the molecular works and immunological analyses have been done at Hannam University and BCG handling and parts of animal studies were performed at Korea Institute of Tuberculosis. They have submitted a manuscript about their results to the Journal of Virology for publication. Their accumulated results were presented by Dr. Bae at a morning session on June 3rd at the 99th Academic Meeting of the American Society for Microbiology held in Chicago for 5 days between 5/30 and 6/3.
Insulin-dependent diabetes mellitus (IDDM), type 1 diabetes well known as a juvenile-onset diabetes, results from the destruction of pancreatic beta cells. Genetic factors and environmental factors have been extensively studied during the last few decades to identify the causative agents for the destruction of pancreatic beta cells. Among the possible environmental factors, several reports have shown that viruses can cause diabetes in human and animals. D variant of EMC virus causes diabetes in SJL/J mice and the EMC virus-induced diabetes is one of the best animal models demonstrating that the virus can be a causative agent in the development of IDDM. Whereas, several live vaccine vehicles are being developed to produce a new generation of safe and effective live recombinant vaccines against a broad spectrum of infectious diseases. Mycobacterium bovis BCG, vaccine strain against tuberculosis (TB), is particularly attractive for this purpose because of its specific characteristics such as low toxicity, immune-enhancing potential, long-lasting immune-inducing capacity, etc.
Dr. Bae and his colleagues have cloned cDNA of the major outer capsid protein VP1 gene of EMC virus into Mycobacterium expression vector, and then introduced into a BCG strain. VP1 protein was efficiently expressed from the recombinant BCG clone, and the VP1 expression lasted stable longer than 4 weeks by a single heat-induction. They immunized SJL/J male mice with the live recombinant BCG. None of the mice immunized with the live recombinant BCG became diabetic when challenged with highly diabetogenic EMC virus. But the control SJL/J mice inoculated with a normal BCG developed diabetes in the same challenge. Antiserum taken from the mice immunized with the recombinant BCG showed having substantial amounts of VP1-specific IgG including high titer of neutralizing antibodies. VP1-specific antibodies were markedly increased as time went on, and reached to the maximum titer at week 10 after a single immunization. The plateau of the titer lasted longer than 4 weeks. Guinea pigs immunized with the live recombinant BCG showed strong delayed type hypersensitivity (DTH) to the VP1 of EMC virus. These mean that the live recombinant BCG elicits efficient humoral and cellular immune response against EMC virus infection, resulting in prevention of virus-induced diabetes during the life in susceptible mice.
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