AUTHOR
Dharmasena MN, Osorio M, Takeda K, Stibitz S, Kopecko DJ
ABSTRACT
We have been exploring the use of the live, attenuated, Salmonella enterica serovar Typhi Ty21a vaccine strain as a versatile oral vaccine vector for the expression and delivery of multiple foreign antigens, including Shigella O-antigens. In this study, we separately cloned genes necessary for the biosynthesis of the S. flexneri serotype 2a and 3a O-antigens, which have been shown previously to provide broad cross-protection to multiple, disease-predominant S. flexneri serotypes. The cloned S. flexneri 2a rfb operon along with, bgt and gtrII, encoded on the SfII bacteriophage were sufficient in Ty21a to express the heterologous S. flexneri 2a O-antigen containing the 3,4 antigenic determinants. Further, this rfb operon along with gtrA, gtrB and gtrX encoded on the Sfx bacteriophage and oac encoded on the Sf6 bacteriophage were sufficient to express S. flexneri 3a O-antigen containing the 6, 7, and 8 antigenic determinants.Ty21a carrying these plasmid-encoded or chromosomally-inserted genes demonstrated simultaneous and stable expression of homologous S. Typhi O-antigen plus the heterologous S. flexneri O-antigen. Candidate Ty21a vaccine strains expressing heterologous S. flexneri 2a or 3a LPS elicited significant serum antibody responses against both homologous S. Typhi and heterologous Shigella LPS and protected mice against virulent S. flexneri 2a or 3a challenges. These new S. flexneri 2a and 3a expressing Ty21a vaccine strains, together with our previously constructed Ty21a strains expressing S. sonnei or S. dysenteriae 1 O-antigens have the potential to be used together for simultaneous protection against the predominant causes of shigellosis worldwide as well as against typhoid fever.
Click here to view the article, published in Clinical and Vaccine Immunology
