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首页> 外文期刊>Vaccine >Discovery of novel cross-protective Rickettsia prowazekii T-cell antigens using a combined reverse vaccinology and in vivo screening approach
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Discovery of novel cross-protective Rickettsia prowazekii T-cell antigens using a combined reverse vaccinology and in vivo screening approach

机译：结合反向疫苗学和体内筛选方法发现新型的交叉保护立克次氏原种立克次氏体T细胞抗原

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Rickettsial agents are some of the most lethal pathogens known to man. Among them, Rickettsia prowazekii is a select agent with potential use for bioterrorism; yet, there is no anti-Rickettsia vaccine commercially available. Owing to the obligate intracellular lifestyle of rickettsiae, CD8(+) T cells are indispensable for protective cellular immunity. Furthermore, T cells can mediate cross-protective immunity between different pathogenic Rickettsia, a finding consistent with the remarkable similarity among rickettsial genomes. However, Rickettsia T cell antigens remain unidentified. In the present study, we report an algorithm that allowed us to identify and validate four novel R. prowazekii vaccine antigen candidates recognized by CD8(+) T cells from a set of twelve in silica-defined protein targets. Our results highlight the importance of combining proteasome-processing as well as MHC class-I-binding predictions. The novel rickettsial vaccine candidate antigens, RP778, RP739, RP598, and RP403, protected mice against a lethal challenge with Rickettsia typhi, which is indicative of cross-protective immunity within the typhus group rickettsiae. Together, our findings validate a reverse vaccinology approach as a viable strategy to identify protective rickettsial antigens and highlight the feasibility of a subunit vaccine that triggers T-cell-mediated cross-protection among diverse rickettsiae
机译：cket病病原体是人类已知的一些最致命的病原体。其中，立克次氏体是一种有潜力用于生物恐怖主义的选择剂。但是，目前尚无商购可得的抗立克次氏体疫苗。由于立克次体的专性细胞内生活方式，CD8（+）T细胞对于保护性细胞免疫是必不可少的。此外，T细胞可以介导不同病原性立克次体之间的交叉保护性免疫，这一发现与立克次氏菌基因组之间的显着相似性是一致的。然而，立克次体T细胞抗原仍未被鉴定。在本研究中，我们报告了一种算法，该算法使我们能够从十二个二氧化硅定义的蛋白质靶物中，鉴定和验证CD8（+）T细胞识别的四个新颖的​​Prowazekii疫苗抗原候选物。我们的结果强调了结合蛋白酶体加工以及MHC I类结合预测的重要性。新型立克次氏菌疫苗候选抗原RP778，RP739，RP598和RP403保护小鼠免受伤寒立克次氏体的致命攻击，这表明斑疹伤寒立克次体具有交叉保护性免疫力。在一起，我们的发现验证了反向疫苗学方法是识别保护立克次体抗原的可行策略，并强调了在多种立克次体之间触发T细胞介导的交叉保护作用的亚单位疫苗的可行性。

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