Construction of Stable and Non-resistant Bivalent Vaccine Candidate Strain Against Shigella flexneri 2a and Shigella sonnei
稳定、无抗药的痢疾福氏2a和宋内双价菌苗候选株的构建

The E. coli cs3 gene coding for CFA/11 antigen was site-specifically integrated into the asd gene locus of S. flexneri 2a vaccine strain T32, resulting in the asd gene inactivated. Meanwhile, the S. sonnei O antigen gene was cloned into a non-resistant expression vector pXL378 to construct the plasmid pXL390. By transforming the asd minus T32 strain with pXL390, the bivalent vaccine candidate strain FS01 against S. flexneri 2a and S. sonnei was finally obtained. Experiments showed that the recombinant plasmid pXL390 was very stable in the asd minus T32 strain without the use of any antibiotics; FS01 strain was genetically stable and expressed two kinds of Shigella LPS-O antigens with no enhancement of its toxicity. Animal test demonstrated that FS01 strain, when administered subcutaneously in mice,could confer 100% protection against the intraperi-toneal challenges of virulent S. flexneri 2a and S. sonnei.