Core-linked LPS expression ofShigella dysenteriaeserotype 1 O-antigen in liveSalmonellaTyphi vaccine vector Ty21a: Preclinical evidence of immunogenicity and protection

• Published in: Vaccine Vol. 25; no. 33; p. 6167
• Main Authors: Xu, De Qi, Cisar, John O, Osorio, Manuel, Wai, Tint T, Kopecko, Dennis J
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Limited 14-08-2007
• Subjects: Bacteriology; Biosynthesis; Gene loci; Immunization; Immunogenicity; Plasmids; Vaccines; Waterborne diseases
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2007.06.003

Shigella dysenteriaeserotype 1 (S. dysenteriae1) causes severe shigellosis that is typically associated with high mortality. Antibodies againstShigellaserotype-specific O-polysaccharide (O-Ps) have been shown to be host protective. In this study, therfblocus and therfpgene with their cognate promoter regions were PCR-amplified fromS. dysenteriae1, cloned, and sequenced. Deletion analysis showed that eightrfbORFs plusrfpare necessary for biosynthesis of this O-Ps. A tandemly-linkedrfb-rfpgene cassette was cloned into low copy plasmid pGB2 to create pSd1. AvirulentSalmonella entericaserovar Typhi (S. Typhi) Ty21a harboring pSd1 synthesizedS. Typhi 9, 12 LPS as well as typical core-linkedS. dysenteriae1 LPS. Animal immunization studies showed that Ty21a (pSd1) induces protective immunity against high stringency challenge with virulentS. dysenteriae1 strain 1617. These data further demonstrate the utility ofS. Typhi Ty21a as a live, bacterial vaccine delivery system for heterologous O-antigens, supporting the promise of a bifunctional oral vaccine for prevention of shigellosis and typhoid fever.