Shigella flexneri (S. flexneri), a leading cause of bacillary dysentery, is a major public health concern particularly affecting children in developing nations.We have constructed a novel attenuated Salmonella vaccine system based on the regulated delayed antigen synthesis (RDAS) and regulated delayed expression of attenuating phenotype (RDEAP) systems for delivering the S. flexneri 2a (Sf2a) O-antigen.Methods: The new Salmonella vaccine platform was constructed through chromosomal integration of the araC P BAD lacI and araC P BAD wbaP cassettes, resulting in a gradual depletion of WbaP enzyme.An expression vector, encoding Sf2a O-antigen biosynthesis under the control of the LacI-repressible P trc promoter, was maintained in the Salmonella vaccine strain through antibiotic-independent selection.Mice immunized with the vaccine candidates were evaluated for cell-mediate and humoral immune responses.Results: In the presence of exogenous arabinose, the Salmonella vaccine strain synthesized native Salmonella LPS as a consequence of WbaP expression.Moreover, arabinose supported LacI expression, thereby repressing Sf2a O-antigen production.In the absence of arabinose in vivo, native Salmonella LPS synthesis is repressed whilst the synthesis of the Sf2a O-antigen is induced.Murine immunization with the Salmonella vaccine strain elicited robust Sf2a-specific protective immune responses together with long term immunity.Conclusion: These findings demonstrate the protective efficacy of recombinant Sf2a O-antigen delivered by a Salmonella vaccine platform.
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Su et al. (2019) studied this question.