Live vaccines give rise to better and longer-lasting anti-tuberculous immunity than killed or sub-unit vaccines. Live BCG is the only licenced tuberculosis vaccine in the US but it does little to protect adults against this highly infectious disease. Mice vaccinated with a sublethal inoculum of M. tuberculosis H37Rv develop high levels of protection against an aerogenic challenge infection with M. tb. Erdman given 1 to 3 months later. The avirulent H37Ra vaccine is very safe but induces little or no immunity against this disease. Virulence genes transferred from H37Rv to H37Ra by electoroporation restore the ability of the attenuated recombinant to grow and survive within the spleens of vaccinated animals. The vaccinated mice were challenge 1 - 2 months later with a small aerogenic inoculum of M. tb Erdman and the growth of the organisms in the lungs and the rate of spread to the spleen are compared to that seen in control mice vaccinated with live BCG or the vector control. M. smegmatis is a non-pathogenic rapid grower widely used in biochemical and genetic studies. Recombinant strains containing large fragments of DNA harvested from virulent M. Tb Erdman were introduced into naive C57BL/6 mice by the intravenous, subcutaneous, intranasal and aerogenic routes and the growth was followed for up to 1 month. All of the mice survived, even when challenged with massive doses of the recombinant. The rM. smegmatis failed to grow in vivo and was rapidly eliminated from the lungs and spleen. Challenge of the vaccinated mice indicated that their resistance to M. tb was no better than the unvaccinated controls.
