Core-linked LPS expression of Shigella dysenteriae serotype 1 O-antigen in live Salmonella Typhi vaccine vector Ty21a: preclinical evidence of immunogenicity and protection.
Core-linked LPS expression of Shigella dysenteriae serotype 1 O-antigen in live Salmonella Typhi vaccine vector Ty21a: preclinical evidence of immunogenicity and protection.
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DOI：
10.1016/j.vaccine.2007.06.003
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发表时间：
2007-08
期刊：
影响因子：
5.5
通讯作者：
De-qi Xu;J. Cisar;M. Osorio;T. Wai;D. Kopecko
中科院分区：
文献类型：
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作者：
De-qi Xu;J. Cisar;M. Osorio;T. Wai;D. Kopecko
志贺菌血清1型（S. 1）引起严重的志贺氏菌病，通常与高死亡率相关。针对志贺氏菌型特异性O-多糖（O-Ps）的抗体已被证明具有宿主保护性。本研究利用PCR技术从S.将其克隆并测序。缺失分析表明，8个rfb ORF加上rfp是该O-Ps生物合成所必需的。将串联连接的rfb-rfp基因盒克隆到低拷贝质粒pGB 2中以产生pSd 1。伤寒沙门氏菌（Salmonella enterica serovar Typhi）Typhi）Ty 21 a（含pSd 1）合成的S.伤寒9，12 LPS以及典型的核心连接的S.紫茎泽兰1 LPS.动物免疫研究表明Ty 21 a（pSd 1）诱导了针对强毒沙门氏菌高强度攻击的保护性免疫。菌株1617.这些数据进一步证明了S. Typhi Ty 21 a作为异源O抗原的活细菌疫苗递送系统，支持预防志贺氏菌病和伤寒的双功能口服疫苗的前景。
Shigella dysenteriae serotype 1 (S. dysenteriae 1) causes severe shigellosis that is typically associated with high mortality. Antibodies against Shigella serotype-specific O-polysaccharide (O-Ps) have been shown to be host protective. In this study, the rfb locus and the rfp gene with their cognate promoter regions were PCR-amplified from S. dysenteriae 1, cloned, and sequenced. Deletion analysis showed that eight rfb ORFs plus rfp are necessary for biosynthesis of this O-Ps. A tandemly-linked rfb–rfp gene cassette was cloned into low copy plasmid pGB2 to create pSd1. Avirulent Salmonella enterica serovar Typhi (S. Typhi) Ty21a harboring pSd1 synthesized S. Typhi 9, 12 LPS as well as typical core-linked S. dysenteriae 1 LPS. Animal immunization studies showed that Ty21a (pSd1) induces protective immunity against high stringency challenge with virulent S. dysenteriae 1 strain 1617. These data further demonstrate the utility of S. 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.