Visceral leishmaniasis (VL) is a tropical and subtropical disease which is endemic in more than eighty countries around the world. Leishmania infantum is one of the main causative agents of VL disease. Currently, there is no approved-to-market vaccine for VL therapy. In this study, we evaluated cellular and humoral immune responses induced by our newly designed multi-epitope vaccine in BALB/c mice. Four antigenic proteins, including histone H1, sterol 24-c-methyltransferase (SMT), Leishmania-specific hypothetical protein (LiHy), and Leishmania-specific antigenic protein (LSAP) were chosen for the prediction of potential immunodominant epitopes. Moreover, to enhance vaccine immunogenicity, two toll-like receptors 4 (TLR4) agonists, resuscitation-promoting factors of Mycobacterium tuberculosis (RpfE and RpfB), were employed as the built-in adjuvants. Immunization with the designed multi-epitope vaccine elicited a robust Th1-type immune response, compared to other groups, as shown by increased levels of IL-2, IFN-γ, TNF-α, and IgG2a. Furthermore, a significant decrease was observed in Th-2-type-related cytokines such as IL-4 in immunized mice. The designed construct also induced a significant reduction in parasite load (p < 0.0001), conferring protection against L. infantum challenge. This study could be promising in gaining insight towards the potential of peptide epitope-based vaccines as effective protective approaches against Leishmania species.

中文翻译：

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一种新的多表位肽疫苗可诱导BALB / c小鼠产生免疫反应并抵抗婴儿利什曼原虫。

内脏利什曼病（VL）是一种热带和亚热带疾病，在世界八十多个国家中流行。婴儿利什曼原虫是VL病的主要病原体之一。当前，尚无用于VL治疗的批准上市疫苗。在这项研究中，我们评估了我们新设计的多表位疫苗在BALB / c小鼠中诱导的细胞和体液免疫反应。四种抗原蛋白，包括组蛋白H1，固醇24-c-甲基转移酶（SMT），利什曼原虫特异性假设蛋白（LiHy）和利什曼原虫选择特异性抗原蛋白（LSAP）预测潜在的免疫优势表位。此外，为了增强疫苗的免疫原性，采用了两种Toll样受体4（TLR4）激动剂，即结核分枝杆菌的复苏促进因子（RpfE和RpfB）作为内置佐剂。IL-2，IFN-γ，TNF-α和IgG2a的水平升高表明，与其他组相比，使用设计的多表位疫苗进行的免疫引起了强烈的Th1型免疫应答。此外，在免疫小鼠中观察到与Th-2型相关的细胞因子如IL-4的显着降低。设计的构建体还诱导了寄生虫负荷的显着降低（p  <0.0001），从而赋予了对婴儿乳杆菌的保护作用。挑战。这项研究有望获得对基于肽表位的疫苗作为利什曼原虫物种有效保护方法的潜力的见识。