Development of a Live Attenuated Bivalent Oral Vaccine Against Shigella sonnei Shigellosis and Typhoid Fever.
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.
Protein Potential LLC.
Yun
Y
Wu
Sanaria Inc., Rockville, Maryland.
Sumana
S
Chakravarty
Protein Potential LLC.
Minglin
M
Li
Protein Potential LLC.
Tint T
TT
Wai
Protein Potential LLC.|Sanaria Inc., Rockville, Maryland.
Stephen L
SL
Hoffman
Protein Potential LLC.
B Kim Lee
BK
Sim
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D004405:Dysentery, Bacillary / Q000517:prevention & control*; D005260:Female; D008807:Mice, Inbred BALB C; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology; D022281:Shigella Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012764:Shigella sonnei / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D014435:Typhoid Fever / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D022281:Shigella Vaccines; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
Shigella sonnei; Ty21a; acid resistance; shigellosis; typhoid fever; vaccine