Hartman A B, Venkatesan M M
Department of Enteric Infections, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100, USA.
Infect Immun. 1998 Sep;66(9):4572-6. doi: 10.1128/IAI.66.9.4572-4576.1998.
Construction of a stable Shigella sonnei vaccine has been complicated by the instability of the virulence phenotype caused by the spontaneous loss of the invasion plasmid. To select a suitable candidate for vaccine construction, 16 S. sonnei strains were screened for stability of the virulence phenotype. A stable strain, S. sonnei Mosely, was selected for further work. pDeltavirG2, a deletion derivative of the virG gene in the sacB suicide vector pCVD442, was used to generate an S. sonnei virG deletion strain, WRSS1, which was invasive in HeLa cells but negative in the Sereny test. WRSS1 was found to be both immunogenic and protective in the guinea pig keratoconjunctivitis model.
侵袭质粒的自发丢失导致毒力表型不稳定,这使得构建稳定的宋内志贺氏菌疫苗变得复杂。为了选择适合构建疫苗的候选菌株,对16株宋内志贺氏菌菌株进行了毒力表型稳定性筛选。选择了一株稳定的菌株——宋内志贺氏菌莫斯利菌株用于进一步研究。使用自杀载体pCVD442中virG基因的缺失衍生物pDeltavirG2构建了一株宋内志贺氏菌virG缺失菌株WRSS1,该菌株在HeLa细胞中具有侵袭性,但在塞雷尼试验中呈阴性。研究发现,WRSS1在豚鼠角膜结膜炎模型中具有免疫原性和保护性。