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Infection with an Avirulent phoP Mutant of Neisseria meningitidis Confers Broad Cross-Reactive Immunity

机译:脑膜炎奈瑟氏球菌无毒phoP突变体的感染具有广泛的交叉反应性免疫力

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Successful vaccines against serogroup A and C meningococcal strains have been developed, but current serogroup B vaccines provide protection against only a limited range of strains. The ideal meningococcal vaccine would provide cross-reactive immunity against the variety of strains that may be encountered in any community, but it is unclear whether the meningococcus possesses immune targets that have the necessary level of cross-reactivity. We have generated a phoP mutant of the meningococcus by allele exchange. PhoP is a component of a two-component regulatory system which in other bacteria is an important regulator of virulence gene expression. Inactivation of the PhoP-PhoQ system in Salmonella leads to avirulence, and phoP mutants have been shown to confer protection against virulent challenge. These mutants have been examined as potential live attenuated vaccines. We here show that a phoP mutant of the meningococcus is avirulent in a mouse model of infection. Moreover, infection of mice with the phoP mutant stimulated a bactericidal immune response that not only killed the infecting strain but also showed cross-reactive bactericidal activity against a range of strains with different serogroup, serotype, and serosubtyping antigens. Sera from the mutant-infected mice contained immunoglobulin G that bound to the surface of a range of meningococcal strains and mediated opsonophagocytosis of meningococci by human phagocytic cells. The meningococcal phoP mutant is thus a candidate live, attenuated vaccine strain and may also be used to identify cross-reactive protective antigens in the meningococcus.
机译:已经开发出针对血清群A和C脑膜炎球菌菌株的成功疫苗,但是目前的血清群B疫苗仅针对有限范围的菌株提供保护。理想的脑膜炎球菌疫苗将提供针对任何社区可能遇到的多种菌株的交叉反应性免疫力,但是尚不清楚脑膜炎球菌是否具有具有必要交叉反应性水平的免疫靶标。我们已经通过等位基因交换产生了脑膜炎球菌的 phoP 突变体。 PhoP是两组分调节系统的组成部分,在其他细菌中,它是毒力基因表达的重要调节剂。沙门氏菌(Salmonella)中PhoP-PhoQ系统的失活会导致无毒力,并且显示 phoP 突变体可提供针对强毒攻击的保护作用。这些突变体已被视为潜在的减毒活疫苗。我们在这里显示脑膜炎球菌的 phoP 突变体在小鼠感染模型中是无毒的。而且,用 phoP 突变体感染的小鼠刺激了杀菌免疫反应,不仅杀死了感染菌株,而且还针对一系列具有不同血清群,血清型和血清分型抗原的菌株表现出交叉反应杀菌活性。 。来自突变感染小鼠的血清含有免疫球蛋白G,其与一系列脑膜炎球菌菌株的表面结合,并由人吞噬细胞介导脑膜炎球菌的调理吞噬作用。因此,脑膜炎球菌 phoP 突变体是候选的减毒活疫苗株,也可用于鉴定脑膜炎球菌中的交叉反应性保护性抗原。

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