COMPARISON OF IMMUNE-RESPONSES OF MICE IMMUNIZED WITH 5 DIFFERENT MYCOBACTERIUM-BOVIS BCC VACCINE STRAINS

Among the various parameters which may contribute to Mycobacterium bov is BCG vaccination efficiency, the choice of the vaccine strain may pl ay an important role. In the present study, we therefore compared the immunogenicity of five different BCG strains that are commonly used fo r BCG vaccine production (Glaxo 1077, Japanese 172, Pasteur 1173P2, Pr ague, and Russian strains), The comparison of the growth capacity of t hese BCG strains in BALB/c and C3H mice demonstrated that a great diff erence exists between the capacity of various BCG strains to multiply and persist in target organs. A much lower recovery of BCG could be sh own in mice immunized with Prague and Japanese BCG strains, T-cell res ponses of BCG-immunized mice were also examined by analyzing T-cell pr oliferative responses, cytokine production, delayed-type hypersensitiv ity responses, and cytotoxic activity. All these assays demonstrated t hat BCG immunization induced strong CD4(+) T-cell responses, mostly of the Th1 type, as demonstrated by interleukin-2 and gamma interferon p roduction, These studies also demonstrated that there are differences between BCG strains in stimulating these T-cell responses. A lack of i nduction of cytotoxic activity was observed following immunization wit h the Japanese strain. Lower anti-purified protein derivative antibody responses were also observed after intravenous or oral immunization w ith this BCG strain, Finally, the protective activity of these BCG str ains was tested by measuring the capacity of immunized mice to elimina te recombinant Pasteur and Japanese BCG strains which expressed beta-g alactosidase. The results of these experiments clearly demonstrated th at the Prague and Japanese strains were unable to protect mice against a second mycobacterial challenge whereas mice immunized with the Glar e, Pasteur, or Russian strain eliminated the recombinant BCG very effi ciently. Altogether, the results of the present study strongly support the view that there are considerable differences in the immunogenicit y of various BCG vaccine strains and that these differences may play a major role in BCG vaccination efficiency.