Ahmed Z U, Sarker M R, Sack D A
Bacterial Genetics Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka.
Vaccine. 1990 Apr;8(2):153-8. doi: 10.1016/0264-410x(90)90139-d.
As an approach to the development of attenuated strains, thymine-requiring (Thy-) and temperature-sensitive (Ts-) single and double mutants of Shigella flexneri Y have been isolated by u.v. mutagenesis and selection. The mutants retained the 140 MDa plasmid, were Sereny-negative and avirulent in 'conditioned' rabbits and in monkeys. Rabbits and monkeys immunized orally with two doses of the mutants were solidly protected against disease and lethality when challenged with the homologous virulent strain. The immunized animals had higher levels of antibodies reactive to the lipopolysaccharide of the wild type strain and also a shorter duration of shedding of the challenge bacteria. It was concluded that Thy- and Ts- mutants of Shigella spp. are highly attenuated and immunogenic to be considered for further studies towards the development of vaccine candidates.
作为减毒株开发的一种方法，通过紫外线诱变和筛选，分离出了弗氏志贺菌Y的胸腺嘧啶需求型（Thy-）和温度敏感型（Ts-）单突变体及双突变体。这些突变体保留了140 MDa质粒，在“预处理”的兔子和猴子中呈血清学阴性且无毒力。用两剂突变体口服免疫的兔子和猴子在受到同源强毒株攻击时，能得到可靠的疾病和致死保护。免疫动物针对野生型菌株脂多糖的反应性抗体水平更高，且攻击细菌的排出持续时间更短。得出的结论是，志贺菌属的Thy-和Ts-突变体高度减毒且具有免疫原性，可考虑进一步研究以开发候选疫苗。
