Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
J Biomol Struct Dyn. 2024;42(22):12505-12522. doi: 10.1080/07391102.2023.2270699. Epub 2023 Oct 24.
Available COVID-19 vaccines are primarily based on SARS-CoV-2 spike protein (S). Due to the emergence of new SARS-CoV-2 variants, other virus proteins with more conservancy, such as Membrane (M) protein, are desired for vaccine development. The reverse vaccinology approach was employed to design a multi-epitope SARS-CoV-2 vaccine candidate based on S and M proteins. Cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), linear B-lymphocyte (LBL) and conformational B-lymphocyte (CBL) of S and M proteins were predicted and screened to choose the best epitopes. A multi-epitope vaccine candidate was constructed using selected CTL, HTL and LBL epitopes. The efficiency of the construct in binding to some immune receptors and an RBD-potent neutralizing monoclonal antibody (bebtelovimab) was predicted, and its immunogenicity was simulated. Finally, cloning of the constructed gene was performed. The potency of our construct as a SARS-CoV-2 vaccine was validated using several bioinformatics tools. The simulation results showed that the construct can induce both cellular and humoral immune responses by producing appropriate cytokines, and it can even create an excellent immune memory response. Furthermore, the designed construct interacts with innate immune receptors such as TLR2 and TLR4 and the terminal variable domain of bebtelovimab with high affinity. We developed a multi-epitope construct based on the S and M proteins of the SARS-CoV-2 virus with high immunogenicity potential using the most up-to-date immunoinformatics and computational biology approaches. The actual efficiency of this multi-epitope vaccine should be further evaluated and studies.Communicated by Ramaswamy H. Sarma.
可用的 COVID-19 疫苗主要基于 SARS-CoV-2 刺突蛋白（S）。由于新的 SARS-CoV-2 变体的出现，人们希望开发其他具有更高保守性的病毒蛋白，如膜（M）蛋白。采用反向疫苗学方法，基于 S 和 M 蛋白设计了一种多表位 SARS-CoV-2 疫苗候选物。预测和筛选了 S 和 M 蛋白的细胞毒性 T 淋巴细胞（CTL）、辅助性 T 淋巴细胞（HTL）、线性 B 淋巴细胞（LBL）和构象 B 淋巴细胞（CBL）的 CTL、HTL 和 LBL 表位，以选择最佳表位。使用选定的 CTL、HTL 和 LBL 表位构建了一种多表位疫苗候选物。预测了构建体与一些免疫受体和 RBD 强效中和单克隆抗体（bebtelovimab）的结合效率，并对其免疫原性进行了模拟。最后，进行了构建基因的克隆。使用几种生物信息学工具验证了构建体作为 SARS-CoV-2 疫苗的效力。模拟结果表明，该构建体通过产生适当的细胞因子诱导细胞和体液免疫反应，甚至可以产生出色的免疫记忆反应。此外，设计的构建体与先天免疫受体（如 TLR2 和 TLR4）以及 bebtelovimab 的末端可变结构域以高亲和力相互作用。我们使用最新的免疫信息学和计算生物学方法，基于 SARS-CoV-2 病毒的 S 和 M 蛋白开发了一种具有高免疫原性潜力的多表位构建体。该多表位疫苗的实际效率应进一步评估和研究。由 Ramaswamy H. Sarma 交流。
