INDUCTION OF A TYPE-1 IMMUNE-RESPONSE TO A RECOMBINANT ANTIGEN FROM MYCOBACTERIUM-TUBERCULOSIS EXPRESSED IN MYCOBACTERIUM-VACCAE

A 19-kDa lipoprotein from Mycobacterium tuberculosis was expressed as a recombinant antigen in the nonpathogenic mycobacterial host strain M . vaccae. Immunization of mice with the recombinant M. vaccae resulted in induction of a strong type 1 immune response to the 19-kDa antigen , characterized by immunoglobulin G2a (IgG2a) antibodies and gamma int erferon (IFN-gamma) production by splenocytes. Immunization with the s ame antigen in incomplete Freund's adjuvant induced a strong IgC1 resp onse with only low levels of IFN-gamma. Subsequent intravenous and aer osol challenges of immunized mice with virulent M. tuberculosis demons trated no evidence of protection associated with the response to the 1 9-kDa antigen: in fact, the presence of the recombinant 19-kDa antigen abrogated the limited protection conferred by M. vaccae (vector contr ol). The recombinant Af. vaccae system is a convenient approach to ind uction of type 1 responses to M. tuberculosis antigens. However, the u nexpected reduction in protective efficacy of M. vaccae expressing the 19-kDa antigen highlights the complexity of testing recombinant subun it vaccines and the need for a better understanding of the immune mech anisms required for effective vaccination against tuberculosis.