Development of a live attenuated bivalent oral vaccine against Shigella sonnei shigellosis and typhoid fever


Wu Y., Chakravarty S., Li M., Wai T.T., Hoffman S.L., Sim BK.


Shigella sonnei (Ss) and Salmonella Typhi cause significant morbidity and mortality. We exploited the safety record of the oral, attenuated S. Typhi vaccine (Ty21a) by utilizing it as a vector to develop a bivalent oral vaccine to protect against Ss shigellosis and typhoid fever. We recombineered the Ss form I O-antigen gene cluster into the Ty21a chromosome to create Ty21a-Ss, which stably expresses Ss form I O-antigen. To enhance survivability in the acid environment of the stomach, we created an acid resistant strain, Ty21a-AR-Ss, by inserting Shigella glutaminase-glutamate decarboxylase systems co-expressed with Ss form I O-antigen gene. Mice immunized intranasally (IN) with Ty21a-AR-Ss produced antibodies against Ss and S. Typhi, and survived lethal IN Ss challenge. This paves the way for proposed GMP manufacture and clinical trials intended to test the clinical effectiveness of Ty21a-AR-Ss in protecting against Ss shigellosis and typhoid fever as compared to the current Ty21a vaccine.

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