Everest P, Frankel G, Li J, Lund P, Chatfield S, Dougan G
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, UK.
FEMS Microbiol Lett. 1995 Feb 1;126(1):97-101. doi: 10.1111/j.1574-6968.1995.tb07398.x.
Attenuated Salmonella strains are currently being evaluated as live vectors for the delivery of heterologous antigens to the mammalian mucosal and systemic immune systems. An approach to improving the stability of heterologous antigen expression during vaccination is to drive expression of the foreign protein from promoters, e.g. nirB, that become activated when Salmonella enter the host. Salmonella strains were constructed that harboured similar multicopy plasmids encoding the lacZ gene. In each strain, lacZ expression was driven from either the nirB, htrA or groE promoters. Expression of LacZ increased in all vaccine strains as they were shifted from conditions of low to high temperature. In addition, expression of lacZ driven from the htrA and nirB promoters significantly increased when the Salmonella entered eukaryotic cells, including macrophages. Expression of lacZ from the groE promoter was significantly elevated in macrophages but not in cells derived from epithelia. These promoters may be useful for optimising heterologous antigen expression within immune cells of the host.
减毒沙门氏菌菌株目前正在作为活载体进行评估，用于将异源抗原递送至哺乳动物的黏膜和全身免疫系统。一种在疫苗接种期间提高异源抗原表达稳定性的方法是从沙门氏菌进入宿主时被激活的启动子（如nirB）驱动外源蛋白的表达。构建了携带编码lacZ基因的类似多拷贝质粒的沙门氏菌菌株。在每个菌株中，lacZ表达由nirB、htrA或groE启动子驱动。随着所有疫苗菌株从低温条件转变为高温条件，LacZ的表达增加。此外，当沙门氏菌进入包括巨噬细胞在内的真核细胞时，由htrA和nirB启动子驱动的lacZ表达显著增加。来自groE启动子的lacZ在巨噬细胞中表达显著升高，但在上皮来源的细胞中未升高。这些启动子可能有助于优化宿主免疫细胞内的异源抗原表达。
