Live oral Salmonella vaccines: potential use of attenuated strains as carriers of heterologous antigens to the immune system.

Live attenuated strains of salmonellae are showing promise as live oral vaccines against human typhoid fever and other Salmonella infections of man and animals. Attenuation can be achieved by introducing genetically defined, non-reverting mutations into specific genes on the Salmonella chromosome. Mutations in the gal E or aroA genes of Salmonella inhibit the ability of the bacteria to grow in vivo, and strains carrying such lesions are effective vaccines against salmonellosis. Genetic determinants encoding for the expression of potentially protective antigens from heterologous, non-Salmonella pathogens can be readily introduced into these attenuated Salmonella strains. Expression of the heterologous antigen does not affect the ability of the Salmonella host to be used as a Salmonella vaccine. Mice infected orally with a Salmonella typhimurium aroA vaccine expressing the Escherichia coli heat-labile toxin B subunit developed both a secretory and serum antibody response to this antigen. These serum antibodies were able to neutralise the activity of E. coli heat-labile toxin in tissue culture assays. A humoral and cell-mediated (DTH) immune response was detected against beta galactosidase, an intracellular antigen, in mice infected with an aroA vaccine expressing this cloned antigen. The prospects for the development of live Salmonella vaccines as a method for delivering heterologous antigens derived from bacteria, viruses and parasites is discussed.