Immunization with temperature-sensitive mutants of Salmonella typhi induces protection in mice

Temperature-sensitive (TS) mutants of Salmonella typhi were isolated following mutagenesis with nitrosoguanidine and two cycles of enrichment with penicillin and D-cycloserine. Several of the TS mutants were characterized with respect to growth profiles at permissive (29 degrees C) and non-permissive (36 degrees C) temperatures, reversion rates, and the potential for inducing protection against challenge in an animal model. All three TS mutants tested were immunogenic in mice; antibodies measured by enzyme-linked immunosorbent assay were produced following intraperitoneal (i.p.) immunization with three different doses of each of the mutants; i.p. immunization with the same mutants also induced highly significant protection (100%) from i.p. wild-type challenge; and oral immunization with one of the mutants significantly reduced shedding of the wild-type following oral challenge.