Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi infection. Despite the wide range of approaches explored during the last seventy years, an effective prophylactic vaccine is not yet available. Here, we developed a novel recombinant antigen derived from conserved regions of 56 kDa type-specific antigen (TSA56), a major outer membrane protein responsible for genetic heterogeneity and antigenicity, and evaluated it as a protective vaccine antigen. Our findings demonstrate that immunization with conserved blocks of TSA56 (cTSA56) not only provides protective immunity against lethal challenges with the homologous genotype, but also confers significantly better protection against heterologous genotypes than TSA56. Adoptive transfer of CD4+ or CD8+ T cells from immunized mice provided significantly enhanced protection against lethal challenge, whereas immune B cells failed to do so, indicating that cellular immunity against the conserved epitopes plays a protective role. Moreover, immunization with a 10-mer peptide mixture, screened from CD8+ T cell epitopes within the conserved region of TSA56, provided enhanced protection against lethal challenge with O. tsutsugamushi. Therefore, this novel recombinant antigen is a promising candidate for scrub typhus vaccine against a wide range of O. tsutsugamushi genotypes.

中文翻译：

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用由TSA56的保守嵌段组成的重组抗原进行免疫可提供广泛的基因型保护，以防斑疹伤寒。

斑疹伤寒是由东方ient虫感染引起的急性发热性疾病。尽管在过去的七十年中探索了各种各样的方法，但是仍然没有有效的预防性疫苗。在这里，我们开发了一种新的重组抗原，该抗原源自56 kDa类型特异性抗原（TSA56）的保守区域，该区域是负责遗传异质性和抗原性的主要外膜蛋白，并将其评估为保护性疫苗抗原。我们的研究结果表明，用保守的TSA56嵌段（cTSA56）进行免疫接种不仅可以提供针对同基因型致死性攻击的保护性免疫力，而且还可以提供比TSA56更好的针对异源基因型的保护性。来自免疫小鼠的CD4 +或CD8 + T细胞的过继转移可显着增强针对致死性攻击的保护，而免疫B细胞则无法做到这一点，这表明针对保守表位的细胞免疫起着保护作用。而且，用10聚体的肽混合物进行免疫，从TSA56的保守区内的CD8 + T细胞表位中筛选，增强了抵抗protection虫的致死性攻击的保护作用。因此，这种新型重组抗原是针对多种虫基因型的灌木斑疹伤寒疫苗的有前途的候选者。从TSA56保守区内的CD8 + T细胞表位中筛选得到的O.tsutsugamushi可以增强抵抗致命攻击的保护作用。因此，这种新颖的重组抗原是针对多种虫基因型的灌木斑疹伤寒疫苗的有前途的候选者。从TSA56保守区内的CD8 + T细胞表位中筛选得到的O.tsutsugamushi可以增强抵抗致命攻击的保护作用。因此，这种新型重组抗原是针对多种虫基因型的灌木斑疹伤寒疫苗的有前途的候选者。