Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/4/2008
Publication Date: 8/12/2008
Citation: Park, S., Kathaperumal, K., Mcdonough, S.P., Akey, B., Huntley, J., Bannantine, J.P., Chang, Y. 2008. Immunization with a DNA Vaccine Cocktail Induces a Th1 Response and Protects Mice Against Mycobacterium avium subsp. paratuberculosis Challenge. Vaccine. 26(34):4329-4337. Interpretive Summary: Previous experiments showed that a set of five Mycobacterium avium subsp. paratuberculosis proteins could induce a significant immune response in cattle. This led us to believe that perhaps this group of five proteins might provide protective immunity against Johne’s disease, which is caused by Mycobacterium avium subsp. paratuberculosis. Therefore, in this manuscript, we describe the vaccination of mice with DNA that codes for the five proteins. By using this DNA-based vaccine strategy, we were able to demonstrate a type of immune response in mice (called Th1) that should lead to protection from infection with this bacterium. The next steps are to move into cattle with this novel vaccine formulation.
Technical Abstract: Several novel antigens of Mycobacterium avium subsp. paratuberculosis have been studied as vaccine components and their immunogenicity has been evaluated. Previously, we reported that 85 antigen complex (85A, 85B, and 85C), superoxide dismutase (SOD), and 35kDa protein could induce significant lymphocyte proliferation as well as the elaboration of Th1-associated cytokines including IFN-gamma, IL-2, IL-12 and TNF-a. Based on these results, we cloned and expressed 85A, 85B, 85C, SOD, and 35kDa-protein genes into the eukaryotic expression plasmid pVR1020. C57BL/6 mice were immunized three times intramuscularly with the recombinant DNA cocktail and pVR1020 DNA alone as control. A significant reduction in the bacterial burden in the spleen and liver of mice immunized with DNA cocktail as compared to the vector control group was found. Also, the relative severity of the liver and spleen histopathology paralleled with the MAP culture results and showed more multifocal granulomas and acid-fast bacilli in the vector control animals. Moreover, mice immunized with the DNA cocktail developed both CD4+ and CD8+ T cell responses to the recombinant antigens and showed significant lymphocyte proliferation. The Th1 response related cytokine (IFN-') levels increased in splenocytes obtained from immunized animals. These results indicate that the use of a recombinant DNA vaccine can provide protective immunity against mycobacterial infection by inducing a Th1 response.