Vaccine potential for inactivated shigellae.

We used human monocyte-derived dendritic cells (DC) and Balb/c mice as models to establish the immunogenic and protective potential of formalin-inactivated Shigella spp. Incubation of DC with inactivated or live bacteria induced DC maturation and cytokine release. Mice immunized orally or intranasally with killed S. flexneri, S. sonnei, or S. dysenteriae developed IgG and fecal IgA titers to the homologous LPS. Following respiratory challenge with the live homologous organisms, 80-100% survival was seen in all vaccinated groups compared to negligible survival in mice given PBS. Oral or intranasal immunization with an inactivated S. flexneri 2a strain (CVD1203) expressing the CFA/I and CS3 antigens of enterotoxigenic Escherichia coli induced IgG responses to both heterologous antigens. These in vivo and in vitro data indicate that inactivated shigellae retain the ability to interact effectively with key antigen presenting cells and induce protective immune responses in mice.