Department of Infection Control Center of Xiangya Hospital, Central South University, Changsha, Hunan, China.
National Clinical Research Center for Geriatric Disorder, Xiangya Hospital, Changsha, Hunan, China.
Front Immunol. 2023 Mar 13;14:1112816. doi: 10.3389/fimmu.2023.1112816. eCollection 2023.
Since May 2022, cases of monkeypox, a zoonotic disease caused by the monkeypox virus (MPXV), have been increasingly reported worldwide. There are, however, no proven therapies or vaccines available for monkeypox. In this study, several multi-epitope vaccines were designed against the MPXV using immunoinformatics approaches.
Three target proteins, A35R and B6R, enveloped virion (EV) form-derived antigens, and H3L, expressed on the mature virion (MV) form, were selected for epitope identification. The shortlisted epitopes were fused with appropriate adjuvants and linkers to vaccine candidates. The biophysical andbiochemical features of vaccine candidates were evaluated. The Molecular docking and molecular dynamics(MD) simulation were run to understand the binding mode and binding stability between the vaccines and Toll-like receptors (TLRs) and major histocompatibility complexes (MHCs). The immunogenicity of the designed vaccines was evaluated via immune simulation.
Five vaccine constructs (MPXV-1-5) were formed. After the evaluation of various immunological and physicochemical parameters, MPXV-2 and MPXV-5 were selected for further analysis. The results of molecular docking showed that the MPXV-2 and MPXV-5 had a stronger affinity to TLRs (TLR2 and TLR4) and MHC (HLA-A02:01 and HLA-DRB102:01) molecules, and the analyses of molecular dynamics (MD) simulation have further confirmed the strong binding stability of MPXV-2 and MPXV-5 with TLRs and MHC molecules. The results of the immune simulation indicated that both MPXV-2 and MPXV-5 could effectively induce robust protective immune responses in the human body.
The MPXV-2 and MPXV-5 have good efficacy against the MPXV in theory, but further studies are required to validate their safety and efficacy.
自 2022 年 5 月以来，猴痘病例，一种由猴痘病毒（MPXV）引起的人畜共患病，在全球范围内报告的病例越来越多。然而，目前尚无针对猴痘的有效治疗方法或疫苗。在这项研究中，我们使用免疫信息学方法设计了几种针对 MPXV 的多表位疫苗。
选择三个靶蛋白，A35R 和 B6R，包膜病毒（EV）形式衍生的抗原，以及成熟病毒（MV）形式上表达的 H3L，用于表位鉴定。候选疫苗融合了适当的佐剂和接头。评估候选疫苗的生物物理和生物化学特性。进行分子对接和分子动力学（MD）模拟，以了解疫苗与 Toll 样受体（TLRs）和主要组织相容性复合物（MHCs）之间的结合模式和结合稳定性。通过免疫模拟评估设计疫苗的免疫原性。
形成了五种疫苗构建体（MPXV-1-5）。在评估了各种免疫和物理化学参数后，选择 MPXV-2 和 MPXV-5 进行进一步分析。分子对接的结果表明，MPXV-2 和 MPXV-5 与 TLRs（TLR2 和 TLR4）和 MHC（HLA-A02:01 和 HLA-DRB102:01）分子具有更强的亲和力，分子动力学（MD）模拟分析进一步证实了 MPXV-2 和 MPXV-5 与 TLRs 和 MHC 分子的强结合稳定性。免疫模拟的结果表明，MPXV-2 和 MPXV-5 均可在人体内有效诱导强大的保护性免疫反应。
MPXV-2 和 MPXV-5 理论上对 MPXV 具有良好的疗效，但需要进一步研究来验证其安全性和疗效。
