Safety and immunogenicity of Salmonella enterica serovar Typhimurium llaB in mice

Abstract

The safety and immunogenicity of an attenuated recombinant Salmonella vaccine strain, Salmonella enterica serovar Typhimurium llaB, was assessed. This vaccine strain could survive in low pH condition, and its ability of intracellular survival did not differ from that of S. enterica serovar Typhimurium UK1, which is the wild-type of the vaccine strain. The mortality of the mice orally administered with the vaccine strain was 50% at the dose of 10(7) CFU. All mice administered with 105 or 103 CFU of the vaccine strain survived for 3 days postinoculation (pi). However, all mice administered with more than 103 CFU of the vaccine strain died within 3 days pi. To examine the protective effect of the vaccine strain. mice were orally immunized with 10(4) and 10(6) CFU of the bacteria. Control mice were given with 0.5 ml of phosphate buffered saline (PBS). After 8 days, the mice were challenged with 10(9) CFU of S. enterica serovar Typhimurium UK1 and mortality was examined for 5 days. The survival rates of the mice immunized with 10(4) and 10(6) CFU of the vaccine strain were 60% and 80%, respectively, whereas all control mice died within 2 days after challenging. To investigate the immunogenicity of S. enterica serovar Typhimurium HaB, mice were orally immunized with 10(5) or 10(6) CFU ml of the vaccine strain. Five mice of each group were sacrificed at 5 and 12 days after immunization, and results showed that immunization of the vaccine strain led to increases of IgG1, IgG2. and IgM titers against S. enterica serovar Typhimurium UK1 in mouse sera, cytokine expressions such as IL-2, IL-4, IL-6 and IL-10 in spleen.. and the lymphocyte proliferation response to mitogens (concanavalin A or LPS) stimulation.