PROTECTIVE IMMUNITY ELICITED BY RECOMBINANT BACILLE CALMETTE-GUERIN (BCG) EXPRESSING OUTER SURFACE PROTEIN-A (OSPA) LIPOPROTEIN - A CANDIDATE LYME-DISEASE VACCINE

The current vaccine against tuberculosis, Mycobacterium bovis strain b acille Calmette-Guerin (BCG), offers potential advantages as a live, i nnately immunogenic vaccine vehicle for the expression and delivery of protective recombinant antigens (Stover, C. K., V. F. de la Cruz, T. R. Fuerst, J. E. Burlein, L. A. Benson, L. T. Bennett, G. P. Bansal, J . F. Young, M. H. Lee, G. F. Hatfull et al. 1991. Nature [Lond]. 351:4 56; Jacobs, W R., Jr., S. B. Snapper, L. Lugosi and B. R. Bloom. 1990. Curr. Top. Microbiol. Immunol. 155:153; Jacobs, W R., M. Tuckman, and B. R. Bloom. 1987. Nature [Lond.]. 327:532); but as an attenuated int racellular bacterium residing in macrophages, BCG would seem to be bes t suited for eliciting cellular responses and not humoral responses. S ince bacterial lipoproteins are often among the most immunogenic of ba cterial antigens, we tested whether BCG expression of a target antigen as a membrane-associated lipoprotein could enhance the potential for a recombinant BCG vaccine to elicit high-titered protective antibody r esponses to target antigens. Immunization of mice with recombinant BCG vaccines expressing the outer surface protein A (OspA) antigen of Bor relia burgdorferi as a membrane-associated lipoprotein resulted in pro tective antibody responses that were 100-1,000-fold higher than respon ses elicited by immunization with recombinant BCG expressing OspA cyto plasmically or as a secreted fusion protein. Furthermore, these improv ed antibody responses were observed in heterogeneous mouse strains tha t vary in their immune responsiveness to OspA and sensitivity to BCG g rowth. Thus, expression of protective antigens as chimeric membrane-as sociated lipoproteins on recombinant BCG may result in the generation of new candidate vaccines against Lyme borreliosis and other human or veterinary diseases where humoral immunity is the protective response.