BACILLUS-ANTHRACIS PROTECTIVE ANTIGEN, EXPRESSED IN SALMONELLA-TYPHIMURIUM SL-3261, AFFORDS PROTECTION AGAINST ANTHRAX SPORE CHALLENGE

The protective antigen (PA) gene from Bacillus anthracis has been expr essed in Salmonella typhimurium SL 3261 (aroA). Expression was achieve d by cloning the gene after the plac promoter in a high copy number pl asmid The recombinant PA was exported into the periplasm. This constru ct was unstable in vivo and also reduced the colonization ability of t he host S. typhimurium. Mouse-passaging of the recombinant Salmonella resulted in a strain with enhanced colonization ability and increased stability of the plasmid in vivo. This effect appeared to be due to a reduction in copy number of the PA-encoding plasmid. Mice were vaccina ted with recombinant S. typhimurium and adjuvanted PA and challenged w ith virulent B. anthracis. Only mice vaccinated with adjuvanted PA or orally with the mouse-passaged recombinant showed partial protection. The degree of protection observed after oral vaccination with the reco mbinant S. typhimurium was similar to the degree of protection afforde d by adjuvanted PA and suggested that the use of S. typhimurium to del iver PA is art effective approach for inducing protection against B. a nthracis. The results presented also suggest that the degree of protec tion demonstrated in the mouse may not fully indicate the potential of the recombinant Salmonella as an effective vaccine in other species.