Development of acquired immunity to Salmonella.

Salmonella enterica serovar Typhi (S. typhi) causes human typhoid fever, a serious and widespread disease in developing countries. Other Salmonella serovars are associated with food-borne infections. The recent emergence of multi-drug-resistant Salmonella strains highlights the need for better preventive measures, including vaccination. The available vaccines against Salmonella infection do not confer optimal protection. The design of new Salmonella vaccines must be based on the identification of suitable virulence genes and on knowledge of the immunological mechanisms of resistance to the disease. Control and clearance of a vaccine strain rely on the phagocyte oxidative burst, reactive nitrogen intermediates, inflammatory cytokines and CD4(+) TCR-alphabeta(+) T cells and are controlled by genes including NRAMP1 and MHC class II. Vaccine-induced resistance to reinfection requires the presence of Th1-type immunological memory and anti-Salmonella antibodies. The interaction between T and B cells is essential for the development of resistance following vaccination. The identification of immunodeficiencies that render individuals more susceptible to salmonellosis must be taken into consideration when designing and testing live attenuated Salmonella vaccines. An ideal live Salmonella vaccine should therefore be safe, regardless of the immunological status of the vaccinee, but still immunogenic.