Induction of protective immunity against Burkholderia pseudomallei using attenuated mutants with defects in the intracellular life cycle.
Induction of protective immunity against Burkholderia pseudomallei using attenuated mutants with defects in the intracellular life cycle.
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DOI：
10.1016/s0035-9203(08)70022-1
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发表时间：
2008-12-01
影响因子：
2.2
通讯作者：
Steinmetz, Ivo
中科院分区：
文献类型：
--
作者：
Breitbach, Katrin;Kohler, Jens;Steinmetz, Ivo
类鼻疽是由革兰氏阴性杆菌类鼻疽伯克霍尔德氏菌引起的严重传染病。目前没有疫苗可用。我们最近产生并表征了几个高度减毒的转座子突变体，其在B的细胞内生命周期中具有缺陷。假鼻疽在本研究中，我们研究了这些突变体中的六种的保护作用：四种在涉及几种生物合成途径的基因中具有敲除（purN（-），purM（-），hisF（-），pab B（-））;一种假定的脂肪酸-蛋白质连接酶B;和一种假定的蛋白质。所有活的突变体在一定程度上对易感BALB/c小鼠的野生型攻击提供保护。选择嘌呤生物合成途径不同步骤中有缺陷的两个突变体进行进一步研究。突变体30：93与purN基因的缺陷提供了更好的保护，对腹腔内的挑战比突变体56：65，其中含有一个非功能性purM基因。虽然突变体30：93在用B鼻内和腹腔内攻击后赋予对急性致死性疾病的显著保护。对于假鼻疽，疫苗接种不能提供针对慢性形式的类鼻疽的保护。此外，对静脉内攻击没有保护作用。需要进一步的研究来分析具有不同保护潜力的各种减毒活疫苗诱导的免疫应答的确切性质。
Melioidosis is a severe infectious disease caused by the Gram-negative rod Burkholderia pseudomallei. There is currently no vaccine available. We recently generated and characterized several highly attenuated transposon mutants with defects in the intracellular life cycle of B. pseudomallei. In the present study we examined the protective effects of six of these mutants: four harbouring knockouts in genes involved in several biosynthetic pathways (purN(-), purM(-), hisF(-), pabB(-)); a putative lipoate-protein ligase B; and a hypothetical protein. All live mutants conferred protection to some degree against wild-type challenge in susceptible BALB/c mice. Two mutants defective in distinct steps of the purine biosynthetic pathway were selected for further studies. Mutant 30:93 with a defect in the purN gene provided better protection against intraperitoneal challenge than mutant 56:65, which harboured a nonfunctional purM gene. Although mutant 30:93 conferred significant protection against acute fatal disease after intranasal and intraperitoneal challenge with B. pseudomallei, vaccination did not confer protection against chronic forms of melioidosis. Moreover, no protective effect could be seen against intravenous challenge. Further studies are required to analyze the precise nature of the immune response induced by the various live attenuated vaccines with different protective potential.