Protective effects of oral immunization with formalin-inactivated whole-cell Citrobacter rodentium on Citrobacter rodentium infection in mice

Abstract

Evaluation of the efficacy of vaccine candidates that prevent enteropathogenic and enterohemorrhagic Escherichia coli (EPEC/EHEC) infection in mouse models is difficult due to their limited pathogenicity in mice. Citrobacter rodentium, a murine pathogenic bacterium that shares its infection strategy and virulence genes with EPEC/EHEC, has been used as a model pathogen to develop novel vaccine strategies or platforms for these bacteria. However, there are few reports on the comparative effectiveness of novel vaccine platforms as no C. rodentium vaccines have yet been prepared by standard methods such as bacteria attenuation or inactivation. In this study, we investigated the protective effect of the oral administration of formalin-inactivated C. rodentium (Fo-CR) on C. rodentium infection in two mouse strains, C57BL/6 and C3H/HeN, as these strains have different degrees of susceptibility to infection. In C57BL/6 mice, administration of Fo-CR induced significant C. rodentium-specific mucosal and systemic antibody responses, promoted bacterial clearance from the gut and inhibited colonic hyperplasia. Furthermore, in C3H/HeN mice, the administration followed by lethal C. rodentium infection induced significantly high avidity serum IgG specific to C. rodentium and inhibited death, body weight loss, and bacterial invasion to visceral organs. In conclusion, the oral administration of Fo-CR resulted in the protection of mice from C. rodentium infection, indicating that it serves as a reference method for evaluating the efficacy of novel oral vaccine candidates or platforms.