Inactivated Shigella as Effective Vaccines and Vaccine Vectors

Authors

• I Albino-Flores
• S Filippova
• C Marsh
• S Stibitz
• M Osorio

Abstract

Shigellae and Enterotoxigenic Escherichia coli (ETEC) remain major causes of diarrhea among children in developing countries and travelers to these areas. However, currently there are no effective vaccines against these enteric pathogens. Here we present our results examining the vaccine and vector potential of Shigella ghost cells expressing ETEC antigens (CVD1203). Bacterial ghost cells in general have been shown to be immunogenic and possess inherent adjuvant properties2. We have found that mice immunized orally or intranasally with ghost cells of S. flexneri expressing CFA/I and CS3 induced strong IgG titers to the homologous LPS and to the ETEC antigens. We show that these immune responses are protective as vaccinated animals can be protected 100% from challenge with the live homologous Shigella strain compared to negligible survival in mice given PBS. Protective efficacy of the immune response to the ETEC antigens was assessed by challenging mice with a fully virulent bioluminescent ETEC strain given intranasally and following the distribution and clearance of the reporter strain using an IVIS® Imaging System. We have used the rate of clearance of the bioluminescent strain as an indication of vaccine efficacy. Our studies show that naïve mice and mice vaccinated with live or killed cell preparations of CVD1203 display significant differences in the rate of clearance of bioluminescent ETEC in immunized mice 48 hours following intranasal challenge. These studies show that Shigella ghost cells are highly immunogenic and can serve as effective carriers for exogenous antigens such as ETEC fimbrial antigens.

Scientific Focus Area: Microbiology and Infectious Diseases

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