Immunization with components of two iron uptake ABC transporters protects mice against systemic Streptococcus pneumoniae infection

Immunization with components of two iron uptake ABC transporters protects mice against systemic Streptococcus pneumoniae infection
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DOI:
10.1128/iai.69.11.6702-6706.2001
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发表时间:
2001-11-01
影响因子:
3.1
通讯作者:
Paton, JC
Paton, JC
中科院分区:
医学2区
文献类型:
--
作者:
Brown, JS;Ogunniyi, AD;Paton, JC

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最近有相当多的研究基于蛋白质的肺炎链球菌疫苗作为现有的荚膜抗原疫苗的替代品。PiuA和PiaA(以前称为Pit1A和Pit2A)是最近鉴定的S.肺炎铁摄取ABC转运蛋白,其是完全毒力所需的并且可能在细菌细胞膜的表面上表达。我们研究了重组PiuA和PiaA蛋白在小鼠中引发针对S.肺炎。重组PiuA和PiaA都产生了抗体反应,它们彼此交叉反应,但不与肺炎球菌溶血素反应,并与来自9种不同链球菌的相同蛋白反应。肺炎血清型。用重组PiuA和PiaA免疫的小鼠被保护免于系统性攻击,其程度类似于用现有的蛋白质疫苗候选物PdB(遗传修饰的肺炎球菌溶血素类毒素)免疫的小鼠。用PiuA和PiaA两者的组合进行免疫导致相加保护,并且对S的全身感染具有高度保护性。肺炎。因此,PiuA和PiaA是新S.使用蛋白质抗原的肺炎疫苗。
There has been considerable recent research into protein based Streptococcus pneumoniae vaccines as alternatives to the existing capsular antigen vaccines. PiuA and PiaA (formerly Pit1A and Pit2A) are recently identified lipoprotein components of S. pneumoniae iron uptake ABC transporters which are required for full virulence and are likely to be expressed on the surface of the bacterial cell membrane. We investigated the efficacy of recombinant PiuA and PiaA proteins at eliciting protective immunity in mice against systemic infection with S. pneumoniae. Both recombinant PiuA and PiaA generated antibody responses that crossreacted with each other but not with pneumolysin and reacted with identical proteins from nine different S. pneumoniae serotypes. Mice immunized with recombinant PiuA and PiaA were protected against systemic challenge to a degree similar to those immunized with an existing protein vaccine candidate, PdB (a genetically modified pneumolysin toxoid). Immunization with a combination of both PiuA and PiaA resulted in additive protection and was highly protective against systemic infection with S. pneumoniae. PiuA and PiaA are therefore promising additional candidates for a novel S. pneumoniae vaccine using protein antigens.