Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran; Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Department of Medical Biochemical Analysis, Cihan University-Erbil, Kurdistan Region, Iraq.
Int Immunopharmacol. 2023 Oct;123:110725. doi: 10.1016/j.intimp.2023.110725. Epub 2023 Aug 7.
On May 7, 2022, WHO reported a new monkeypox case. By May 2023 over 80,000 cases had been reported worldwide outside previously endemic nations. (This primarily affected the men who have sex with men (MSM) community in rich nations). The present research aims to develop a multi-epitope vaccine for the monkeypox virus (MPXV) using structural and cell surface proteins.
The first part of the research involved retrieving protein sequences. The Immune Epitope Database (IEDB) was then used to analyze the B and T lymphocyte epitopes. After analyzing the sensitizing properties, toxicity, antigenicity, and molecular binding, appropriate linkers were utilizedto connect selected epitopes to adjuvants, and the structure of the vaccine was formulated. Algorithms from the field of immunoinformatics predicted the secondary and tertiary structures of vaccines. The physical, chemical, and structural properties were refined and validated to achieve maximum stability. Molecular docking and molecular dynamic simulations were subsequently employed to assess the vaccine's efficacy. Afterward, the ability of the vaccine to interact with toll-like receptors 3 and 4 (TLR3 and TLR4) was evaluated. Finally, the optimized sequence was then introduced into the Escherichia coli (E. coli) PET30A + vector.
An immunoinformatics evaluation suggested that such a vaccine might be safe revealed that this vaccine is safe, hydrophilic, temperature- and condition-stable, and can stimulate innate immunity by binding to TLR3 and TLR4.
Our findings suggest that the first step in MPXV pathogenesis is structural and cell surface epitopes. In this study, the most effective and promising epitopes were selected and designed throughprecision servers. Furthermore,through the utilization of multi-epitope structures and a combination of two established adjuvants, this research has the potential to be a landmarkin developing an antiviralvaccine against MPXV. However, additional in vitro and in vivo tests are required to confirm these results.
2022 年 5 月 7 日，世界卫生组织报告了一例新的猴痘病例。截至 2023 年 5 月，在以前无地方性流行的国家报告了超过 8 万例全球病例。（这主要影响了富裕国家的男男性行为者（MSM）群体）。本研究旨在使用结构和细胞表面蛋白为猴痘病毒（MPXV）开发一种多表位疫苗。
研究的第一部分涉及检索蛋白质序列。然后使用免疫表位数据库（IEDB）分析 B 和 T 淋巴细胞表位。在分析了致敏特性、毒性、抗原性和分子结合性后，使用合适的接头将选定的表位连接到佐剂上，并制定了疫苗的结构。免疫信息学领域的算法预测了疫苗的二级和三级结构。对物理、化学和结构特性进行了优化和验证，以达到最大稳定性。随后进行了分子对接和分子动力学模拟，以评估疫苗的疗效。之后，评估了疫苗与 toll 样受体 3 和 4（TLR3 和 TLR4）相互作用的能力。最后，将优化后的序列引入大肠杆菌（E. coli）PET30A+载体。
免疫信息学评估表明，这种疫苗可能是安全的，表明这种疫苗是安全的、亲水的、温度和条件稳定的，可以通过与 TLR3 和 TLR4 结合来刺激先天免疫。
我们的研究结果表明，MPXV 发病机制的第一步是结构和细胞表面表位。在这项研究中，通过精密服务器选择和设计了最有效和最有前途的表位。此外，通过利用多表位结构和两种已建立的佐剂的组合，这项研究有可能成为开发针对 MPXV 的抗病毒疫苗的一个里程碑。然而，还需要进行额外的体外和体内试验来证实这些结果。
