Rowaiye Adekunle Babajide, Nwonu Ezinne Janefrances, Asala Titilayo Mercy, Ogu Amoge Chidinma, Bur Doofan, Chukwu Chimaobi, Oli Angus Nnamdi, Agbalalah Tarimoboere
National Biotechnology Development Agency, Abuja, Nigeria.
Department of Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Nigeria.
Clin Exp Vaccine Res. 2022 Sep;11(3):249-263. doi: 10.7774/cevr.2022.11.3.249. Epub 2022 Sep 30.
Lassa fever is a zoonotic acute viral hemorrhagic disease caused by Lassa virus (LASV). There is currently no licensed vaccine for the prevention of the disease. This study is aimed at discovering immunodominant epitopes from the envelope glycoprotein of the Lassa mammarenavirus and designing of a multi-epitope vaccine candidate (VC).
The amino acid sequences of the envelope glycoprotein of 26 strains of LASV from five countries were selected. After evaluation for antigenicity, immunogenicity, allergenicity, and toxicity, immunodominant CD8, CD4, and linear B lymphocytes were also selected. The selected epitopes were modelled and a molecular docking with the appropriate major histocompatibility complex (MHC) proteins was performed. Using an adjuvant and linkers, a multi-epitope VC was designed. The VC was evaluated for its physicochemical and immunological properties and structurally refined, validated, and mutated (disulphide engineering). The complex formed by the VC and the toll-like receptor-4 receptor was subjected to molecular dynamic simulation (MDS) followed by in silico cloning in a plasmid vector.
A VC with 203 sequences, 22.13 kDa weight, isoelectric point of 9.85 (basic), instability index value of 27.62, aliphatic index of 68.87, and GRAVY value of -0.455 (hydrophilic) emerged. The VC is predicted to be non-allergenic with antigenicity, MHC I immunogenicity, and solubility upon overexpression values of 0.81, 2.04, and 0.86 respectively. The VC also has an estimated half-life greater than 10 hours in and showed stability in all the parameters of MDS.
The VC shows good promise in the prevention of Lassa fever but further tests are required to validate its safety and efficacy.
拉沙热是由拉沙病毒（LASV）引起的人畜共患急性病毒性出血热疾病。目前尚无预防该疾病的获批疫苗。本研究旨在从拉沙哺乳病毒的包膜糖蛋白中发现免疫显性表位，并设计一种多表位候选疫苗（VC）。
选取来自五个国家的26株LASV包膜糖蛋白的氨基酸序列。在对抗原性、免疫原性、致敏性和毒性进行评估后，还筛选出了免疫显性CD8、CD4和线性B淋巴细胞表位。对所选表位进行建模，并与合适的主要组织相容性复合体（MHC）蛋白进行分子对接。使用佐剂和连接子设计了一种多表位VC。对VC的理化和免疫学性质进行评估，并进行结构优化、验证和突变（二硫键工程）。对VC与Toll样受体4形成的复合物进行分子动力学模拟（MDS），随后在质粒载体中进行电子克隆。
得到了一个含有203个序列、分子量为22.13 kDa、等电点为9.85（碱性）、不稳定指数值为27.62、脂肪族指数为68.87、亲水性总平均参数（GRAVY）值为 -0.455（亲水性）的VC。预测该VC无致敏性，其抗原性、MHC I免疫原性和过表达时的溶解度值分别为0.81、2.04和0.86。该VC在体外的估计半衰期大于10小时，并且在MDS的所有参数中均表现出稳定性。
该VC在预防拉沙热方面显示出良好前景，但需要进一步试验来验证其安全性和有效性。
