Dikhit Manas Ranjan, Pranav A, Kumar Ajay, Sen Abhik
Department of Bioinformatics, ICMR-Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna 800007, India.
Department of Bioinformatics, ICMR-Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna 800007, India.
Acta Trop. 2025 Apr;264:107600. doi: 10.1016/j.actatropica.2025.107600. Epub 2025 Mar 26.
Leishmania donovani, which is responsible for visceral leishmaniasis (VL), poses severe public health challenges, necessitating novel strategies to decrease its incidence. The epitopes predicted with immune informatics tools provide the opportunity for the development of a good vaccine candidate. The immunogenicity of sand fly salivary proteins SP02, SP12, SP13, SP14, SP15, SP19, and SP56 and known Leishmania MHC class I and class II epitopes was evaluated. Among the sand fly salivary proteins the most prominent ten B cell epitopes based on their immunogenicity, stability and safety were derived from these proteins. Two remarkable vaccination candidates that were considered safe, SP14 and SP15, were "LPTILAHSPAGASVNQ" (1.244) and "RLLIKDYVVTRKVVKD" (1.178), respectively. These T cell epitopes included thirteen verified MHC I and six MHC class II epitopes. All known immunodominant epitopes were used in the vaccine build together with possible linkers and an adjuvant at the N-terminus to improve immunogenicity. The proposed vaccine was extensively tested to establish its stability, non-allergic reaction, and nontoxicity, all of which were confirmed.The vaccine construct's stable interaction with TLR4 highlighted important hydrogen bonds necessary for stable receptor engagement. Indicative of a robust Th1 response, immune simulations showed an elivated IgG and IgM titers, substantial helper and cytotoxic T-cell responses, and elevated levels of IFN-γ, IL-2, and IL-12, further supporting the vaccine construct's potential as a promising candidate for leishmaniasis control. However, experimental validations will determine its potential as an effective vaccine candidate.
杜氏利什曼原虫是内脏利什曼病（VL）的病原体，给公共卫生带来了严峻挑战，因此需要新的策略来降低其发病率。利用免疫信息学工具预测的表位为开发优秀的疫苗候选物提供了机会。对白蛉唾液蛋白SP02、SP12、SP13、SP14、SP15、SP19和SP56以及已知的利什曼原虫MHC I类和II类表位的免疫原性进行了评估。在白蛉唾液蛋白中，根据其免疫原性、稳定性和安全性，从这些蛋白中获得了最突出的十个B细胞表位。两个被认为安全的显著疫苗候选物，SP14和SP15，分别是“LPTILAHSPAGASVNQ”（1.244）和“RLLIKDYVVTRKVVKD”（1.178）。这些T细胞表位包括十三个经过验证的MHC I类和六个MHC II类表位。所有已知的免疫显性表位都被用于构建疫苗，并在N端加入了可能的连接子和佐剂以提高免疫原性。对所提出的疫苗进行了广泛测试以确定其稳定性、无过敏反应和无毒性，所有这些都得到了证实。疫苗构建体与TLR4的稳定相互作用突出了稳定受体结合所需的重要氢键。免疫模拟显示IgG和IgM滴度升高、辅助性和细胞毒性T细胞反应强烈以及IFN-γ、IL-2和IL-12水平升高，这表明有强大的Th1反应，进一步支持了疫苗构建体作为控制利什曼病的有前景候选物的潜力。然而，实验验证将确定其作为有效疫苗候选物的潜力。
