具有两种减毒标记的福氏志贺菌2a和宋内志贺菌活疫苗候选菌株。I. 构建具有保留侵袭力但细胞内增殖减少的疫苗候选菌株。

Live Shigella flexneri 2a and Shigella sonnei I vaccine candidate strains with two attenuating markers. I. Construction of vaccine candidate strains with retained invasiveness but reduced intracellular multiplication.

作者信息

Linde K, Dentchev V, Bondarenko V, Marinova S, Randhagen B, Bratoyeva M, Tsvetanov Y, Romanova Y

机构信息

Institute of Medical Microbiology and Epidemiology, Karl Marx University, Leipzig, GDR.

出版信息

Vaccine. 1990 Feb;8(1):25-9. doi: 10.1016/0264-410x(90)90173-j.

DOI:10.1016/0264-410x(90)90173-j

PMID:2180230

Abstract

Live Shigella flexneri 2a and Shigella sonnei Phase I vaccine candidate strains with two virulence-reducing markers were constructed through stepwise incorporation of weakly attenuating purine auxotrophy with subsequent rifampicin-resistance (RNA polymerase) mutation to yield optimal attenuation. These vaccine candidate strains showed an unaltered plasmid profile; did not cause keratoconjunctivitis in the Sereny test, while being excreted for a short but still marked period and providing partial protection from wild-strain infection; exhibited for guinea-pig conjunctival epithelia, HeLa cells and rat enterocytes a maintained invasiveness with reduced intracellular multiplication with little, if any, reversible cell damage; and produced, just as their ultrasonic lysates, no exudative reaction in the rabbit gut loop test.

摘要

通过逐步引入弱减毒嘌呤营养缺陷型并随后进行利福平抗性（RNA 聚合酶）突变以实现最佳减毒，构建了具有两种毒力降低标记的活福氏志贺菌 2a 型和宋内志贺菌 I 期疫苗候选菌株。这些疫苗候选菌株显示出质粒图谱未改变；在 Sereny 试验中不引起角膜结膜炎，同时在短但仍显著的时期内排出，并提供对野生菌株感染的部分保护；对豚鼠结膜上皮、HeLa 细胞和大鼠肠上皮细胞表现出维持的侵袭性，细胞内增殖减少，细胞损伤极少（如果有的话）且几乎没有可逆性；并且，正如它们的超声裂解物一样，在兔肠环试验中不产生渗出反应。