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首页> 外文期刊>Infection and immunity >Construction and characterization of a Vi-positive variant of the Salmonella typhi live oral vaccine strain Ty21a.
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Construction and characterization of a Vi-positive variant of the Salmonella typhi live oral vaccine strain Ty21a.

机译:伤寒沙门氏菌口服活疫苗菌株Ty21a的Vi阳性变异体的构建和表征。

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The viaB locus coding for the Vi antigen of Salmonella typhi Ty2 was cloned on a 40.6-kilobase fragment into the cosmid vector pHC79. The live, oral, attenuated Vi-negative S. typhi Ty21a vaccine strain was transformed with the recombinant cosmid encoding the viaB locus. Homologous recombination of the viaB locus into the chromosome of S. typhi Ty21a was induced by UV irradiation, and Vi-positive recombinants were selected in the presence of D-cycloserine. One such isolate, termed WR4103, contained no plasmids or the attendant antibiotic resistance markers and expressed the Vi antigen stably. Vi antigen extracted from WR4103 was immunologically indistinguishable from Vi antigen purified from S. typhi Ty2. The only detectable difference between Ty21a and WR4103 was in the production of Vi antigen. The mean lethal doses of Ty21a and WR4103 for mice were nearly identical. Immunization of mice with WR4103 engendered a Vi antibody response and afforded complete protection against fatal infection with virulent S. typhi Ty2. Thus, S. typhi WR4103 may serve as an improved oral vaccine for protection against typhoid fever.
机译:将编码伤寒沙门氏菌Ty2的Vi抗原的viaB基因座克隆到一个40.6碱基碱基的片段中,插入粘粒载体pHC79中。用编码viaB基因座的重组粘粒转化活的口服减毒的Vi-伤寒伤寒链球菌Ty21a疫苗株。通过紫外线照射,将viaB基因座同源重组到伤寒沙门氏菌Ty21a染色体中,并在D-环丝氨酸存在下选择Vi阳性重组体。一种这样的分离株,称为WR4103,不包含质粒或伴随的抗生素抗性标记,并且稳定表达Vi抗原。从WR4103提取的Vi抗原与从伤寒沙门氏菌Ty2纯化的Vi抗原在免疫学上没有区别。 Ty21a和WR4103之间唯一可检测的差异是Vi抗原的产生。 Ty21a和WR4103对小鼠的平均致死剂量几乎相同。用WR4103免疫小鼠可产生Vi抗体应答,并提供针对致命性伤寒链球菌Ty2致命感染的完全保护。因此,伤寒沙门氏菌WR4103可以用作预防伤寒的改良口服疫苗。

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