Influence of strain viability and antigen dose on the use of attenuated mutants of Salmonella as vaccine carriers

Abstract

It is now accepted that oral killed typhoid vaccines are not effective at inducing protective anti-typhoid immunity. It is not known whether oral killed Salmonella can function as an effective carrier of other antigens to the immune system. In order to test this hypothesis, we immunized groups of mice with viable and non-viable preparations of aroA Salmonella dublin strain EL23 which codes for production of the binding subunit of the heat-labile enterotoxin of Escherichia coli (LT-B). Animals immunized orally with viable EL23 developed serum and mucosal anti-LT-B responses consistent with our previous findings. Significantly, mice immunized orally with ultraviolet-killed EL23 developed serum and mucosal antibody responses equivalent to those which developed in animals orally immunized with the same number of viable EL23. We extended these observations to include a number of methods of killing the organisms which may also preserve the ability of these strains to function as carriers. Our findings indicate that viability is not a requirement for use of a Salmonella strain as an immunological carrier. Moreover, our evidence indicates that bacteraemia and persistence in tissues are not necessary for oral priming, and therefore it may be best to dissociate the question of what makes the best live oral anti-typhoid vaccine from the question of what makes a good carrier of heterologous antigens.