Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz 616, Nizwa, Sultanate of Oman; Department of Biotechnology and Genetic Engineering, Hazara University Mansehra, 2100, Pakistan.
Institute of Biotechnology and Genetic Engineering, the University of Agriculture Peshawar, Peshawar 25000, Pakistan.
J Infect Public Health. 2023 Feb;16(2):214-232. doi: 10.1016/j.jiph.2022.12.023. Epub 2022 Dec 31.
Lymphocytic choriomeningitis virus (LCMV) infects many individuals worldwide and causes severe infection in the immunosuppressant recipient, spontaneous abortion, and congenital disabilities in infants.
There is no specific vaccine or therapeutics available to protect against LCMV infection; thus, there is a need to design a potential vaccine to combat the virus by developing immunity in the population. Herein, we attempted to design a potent multi-epitope vaccine for LCMV using immunoinformatics methods.
The whole proteome of the virus was screened and mapped to extract immunodominant B-cell and T-cell epitopes which were fused with appropriate linkers (EAAAK, GGGS, AAY, GPGPG, and AAY), PADRE sequence (13aa) and an adjuvant (50 S ribosomal protein L7/L12) to formulate a multi-epitope vaccine ensemble. Codon adaptation and in silico cloning of the constructed vaccine were carried out using bioinformatics tools. The secondary and tertiary structure of the vaccine construct was predicted and refined. The physicochemical profile of the designed vaccine was analyzed, and the multi-epitope vaccine's potential to bind Toll-like receptors (TLR2 and TLR4) was evaluated through molecular docking and molecular dynamics simulations. Computational immune simulation of the designed vaccine antigen was performed using the C-ImmSim server.
The designed multi-epitope-based vaccine (613 aa) comprised 26 immunodominant (six B-cell, nine cytotoxic T lymphocytes, and 11 helper T lymphocytes) epitopes and is predicted antigenic, non-toxic, non-allergen, soluble, and topographically accessible with a suitable physicochemical profile. The designed vaccine is expected to cover a broad worldwide population (96.35 %) and stimulate a robust adaptive immune response against the virus upon administration. In silico cloning of the constructed vaccine in PET28a (+) vector ensured its optimal expression in the Escherichia coli system. Molecular docking, molecular dynamics simulation, and binding free energy estimation collectively support the stability and energetically favourable interaction of the modeled vaccine-TLR2/4 complexes.
The designed multi-epitope vaccine in the present study could serve as a potential vaccine candidate to protect against LMCV infection; however, the experimental validation and safety testing of the vaccine is warranted to validate the study's outcomes.
淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染了世界上许多人，并导致免疫抑制剂受者的严重感染、自发性流产和婴儿先天性残疾。
目前尚无针对 LCMV 感染的特定疫苗或治疗方法；因此，需要通过在人群中产生免疫力来设计一种潜在的疫苗来对抗该病毒。在此，我们尝试使用免疫信息学方法设计一种针对 LCMV 的有效多表位疫苗。
筛选病毒的整个蛋白质组并对其进行映射，以提取免疫优势 B 细胞和 T 细胞表位，然后将其与适当的接头（EAAAK、GGGS、AAY、GPGPG 和 AAY）、PADRE 序列（13 个氨基酸）和佐剂（50S 核糖体蛋白 L7/L12）融合，形成多表位疫苗组合。使用生物信息学工具对构建的疫苗进行密码子适应和体外克隆。预测和优化疫苗构建体的二级和三级结构。分析设计疫苗的物理化学特性，并通过分子对接和分子动力学模拟评估多表位疫苗与 Toll 样受体（TLR2 和 TLR4）结合的潜力。使用 C-ImmSim 服务器对设计的疫苗抗原进行计算免疫模拟。
设计的基于多表位的疫苗（613 个氨基酸）包含 26 个免疫优势（6 个 B 细胞、9 个细胞毒性 T 淋巴细胞和 11 个辅助 T 淋巴细胞）表位，预测具有抗原性、非毒性、非变应原性、可溶性和拓扑可及性，具有合适的物理化学特性。设计的疫苗有望覆盖全球广泛的人群（96.35%），并在接种后刺激针对病毒的强大适应性免疫反应。在 PET28a（+）载体中对构建疫苗进行的体外克隆确保了其在大肠杆菌系统中的最佳表达。分子对接、分子动力学模拟和结合自由能估算共同支持模型疫苗-TLR2/4 复合物的稳定性和能量有利相互作用。
本研究设计的多表位疫苗可以作为预防 LMCV 感染的潜在疫苗候选物；然而，需要对疫苗进行实验验证和安全性测试，以验证研究结果。
