Mandal Saurav, Chanu Waribam Pratibha, Srivastava Rajan, Patgiri Saurav Jyoti, Natarajaseenivasan Kalimuthusamy
Regional Medical Research Centre, Indian Council of Medical Research (ICMR), Dibrugarh, India; Nodal Officer, Model Rural Health Research Unit (MRHRU), Meghalaya, India.
Indian Institute of Science Education and Research (IISER), Thiruvananthapuram, India.
Hum Immunol. 2025 Jul 15;86(4):111346. doi: 10.1016/j.humimm.2025.111346.
Malaria, a potentially fatal disease caused by various Plasmodium species, continues to be a significant global health burden, with Plasmodium falciparum responsible for over 90% of malaria mortality worldwide (Snow, 2015). Current treatments, primarily relying on chemotherapy, face challenges due to drug resistance and severe side effects, highlighting the need for more effective and sustainable solutions. Vaccine-based approaches offer a promising alternative, providing potential long-term immunity with reduced risk of resistance. This study aims to develop a robust multi-epitope vaccine targeting four key Plasmodium falciparum 3D7 proteins: PfPHB1, PfPHB2, PfHSP70, and PfGARP. These proteins were selected based on their crucial roles in the parasite's survival and pathogenicity, as well as their conserved sequences present during the blood stage of infection. Using an array of bioinformatics tools, we identified B cell epitopes, HTL epitopes, and CTL epitopes, ensuring their antigenicity, non-toxicity, and non-allergenicity. These epitopes were then assembled into a vaccine construct, enhanced with the FliC protein of Salmonella typhimurium as an adjuvant to boost the immune response. The vaccine construct's secondary and tertiary structures were predicted and refined using PSIPRED and AlphaFold2, respectively. Molecular docking studies demonstrated strong interactions between the vaccine and TLR5, indicating potential efficacy in inducing an immune response. Codon optimization and in silico cloning in Escherichia coli K12 ensured efficient expression of the vaccine construct. Immune simulation using the C-ImmSim server predicted a robust and comprehensive immune response, further validating the vaccine's potential. This in-silico study represents a significant step towards developing a multi-epitope vaccine for malaria, addressing the limitations of current treatments and paving the way for experimental validation and future clinical trials.
疟疾是由多种疟原虫引起的一种潜在致命疾病，仍然是全球重大的健康负担，其中恶性疟原虫导致了全球超过90%的疟疾死亡（斯诺，2015年）。目前的治疗主要依靠化疗，但由于耐药性和严重的副作用而面临挑战，这凸显了需要更有效和可持续的解决方案。基于疫苗的方法提供了一个有前景的替代方案，可提供潜在的长期免疫力且耐药风险降低。本研究旨在开发一种针对四种关键恶性疟原虫3D7蛋白的强大多表位疫苗：PfPHB1、PfPHB2、PfHSP70和PfGARP。选择这些蛋白是基于它们在寄生虫生存和致病性中的关键作用，以及它们在感染血液阶段存在的保守序列。使用一系列生物信息学工具，我们鉴定了B细胞表位、HTL表位和CTL表位，确保它们的抗原性、无毒性和非致敏性。然后将这些表位组装成疫苗构建体，用鼠伤寒沙门氏菌的FliC蛋白作为佐剂进行增强，以增强免疫反应。分别使用PSIPRED和AlphaFold2预测并优化了疫苗构建体的二级和三级结构。分子对接研究表明疫苗与TLR5之间有强烈的相互作用，表明在诱导免疫反应方面具有潜在疗效。在大肠杆菌K12中进行密码子优化和计算机克隆确保了疫苗构建体的有效表达。使用C-ImmSim服务器进行的免疫模拟预测了强大而全面的免疫反应，进一步验证了疫苗的潜力。这项计算机研究代表了朝着开发疟疾多表位疫苗迈出的重要一步，解决了当前治疗的局限性，并为实验验证和未来的临床试验铺平了道路。
