Evaluation of a phoP/phoQ-deleted, aroA-deleted live oral Salmonella typhi vaccine strain in human volunteers
Evaluation of a phoP/phoQ-deleted, aroA-deleted live oral Salmonella typhi vaccine strain in human volunteers
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DOI：
10.1016/0264-410x(95)00173-x
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发表时间：
1996-01-01
期刊：
影响因子：
5.5
通讯作者：
Miller, SI
中科院分区：
文献类型：
--
作者：
Hohmann, EL;Oletta, CA;Miller, SI
改进的口服伤寒活疫苗可以通过删除伤寒沙门氏菌中的沙门氏菌特异性毒力基因来设计。 Ty445 是一种删除了 aroA 的伤寒沙门氏菌 Ty2 菌株，也删除了 phoP/phoQ 鼠伤寒沙门氏菌毒力调节位点，并在人类志愿者中进行了测试。志愿者接受了逐步增加的单剂量疫苗，随后 14 人接受了两剂 10(10) c.f.u. 疫苗。无明显副作用。对照疫苗接种者接受了四剂口服伤寒活疫苗 Ty21a。在对照中，5/8 发生血清转化（通过 ELISA 中针对伤寒沙门氏菌 O 抗原或全细菌抗原的血清 IgG 的增加来测量）。只有 2/14 接受实验性疫苗 Ty445 的志愿者发生血清转化 尽管 Delta aroA Delta phoP/phoQ S 伤寒菌株用作伤寒疫苗时被过度减毒，但我们的数据表明，伤寒沙门氏菌中 phoP/phoQ 位点的缺失可显着减弱这种人类病原体。
Improved live oral typhoid fever vaccines may be engineered by deletion of Salmonella-specific virulence genes in Salmonella typhi. Ty445, an aroA-deleted S, typhi Ty2 strain also deleted for the phoP/phoQ Salmonella typhimurium virulence regulatory locus, was tested in human volunteers. Volunteers received escalating single doses of the vaccine, subsequently 14 individuals received two doses of 10(10) c.f.u. without significant side-effects. Control vaccinees received four doses of the live oral typhoid vaccine Ty21a. Of controls, 5/8 seroconverted as measured by increases in serum IgG directed against S. typhi O antigen or whole bacterial antigens in ELISAs. Only 2/14 volunteers receiving the experimental vaccine Ty445 seroconverted Although a Delta aroA Delta phoP/phoQ S, typhi strain is overattenuated for use as a typhoid fever vaccine, our data demonstrate that the deletion of the phoP/phoQ locus in S. typhi significantly attenuates this human pathogen.