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- Title
Development of a Live Attenuated Bivalent Oral Vaccine Against Shigella sonnei Shigellosis and Typhoid Fever.
- Authors
Yun Wu; Chakravarty, Sumana; Minglin Li; Wai, Tint T.; Hoffman, Stephen L.; Sim, B. Kim Lee; Wu, Yun; Li, Minglin
- Abstract
Shigella sonnei and Salmonella Typhi cause significant morbidity and mortality. We exploited the safety record of the oral, attenuated S. Typhi vaccine (Ty21a) by using it as a vector to develop a bivalent oral vaccine to protect against S. sonnei shigellosis and typhoid fever. We recombineered the S. sonnei form I O-antigen gene cluster into the Ty21a chromosome to create Ty21a-Ss, which stably expresses S. sonnei 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 coexpressed with S. sonnei form I O-antigen gene. Mice immunized intranasally with Ty21a-AR-Ss produced antibodies against S. sonnei and S. Typhi, and survived lethal intranasal S. sonnei challenge. This paves the way for proposed good manufacturing practices manufacture and clinical trials intended to test the clinical effectiveness of Ty21a-AR-Ss in protecting against S. sonnei shigellosis and typhoid fever, as compared with the current Ty21a vaccine.
- Subjects
ORAL vaccines; SHIGELLA sonnei; TYPHOID vaccines; IMMUNIZATION; GLUTAMINASES
- Publication
Journal of Infectious Diseases, 2017, Vol 215, Issue 2, p259
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiw528