Department of Biotechnology and Genetic Engineering, Hazara University, Mansehra, Pakistan.
Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz, Nizwa, Oman.
Front Immunol. 2023 Jan 26;14:1091941. doi: 10.3389/fimmu.2023.1091941. eCollection 2023.
The current monkeypox (MPX) outbreak, caused by the monkeypox virus (MPXV), has turned into a global concern, with over 59,000 infection cases and 23 deaths worldwide.
Herein, we aimed to exploit robust immunoinformatics approach, targeting membrane-bound, enveloped, and extracellular proteins of MPXV to formulate a chimeric antigen. Such a strategy could similarly be applied for identifying immunodominant epitopes and designing multi-epitope vaccine ensembles in other pathogens responsible for chronic pathologies that are difficult to intervene against.
A reverse vaccinology pipeline was used to select 11 potential vaccine candidates, which were screened and mapped to predict immunodominant B-cell and T-cell epitopes. The finalized epitopes were merged with the aid of suitable linkers, an adjuvant (Resuscitation-promoting factor), a PADRE sequence (13 aa), and an HIV TAT sequence (11 aa) to formulate a multivalent epitope vaccine. Bioinformatics tools were employed to carry out codon adaptation and computational cloning. The tertiary structure of the chimeric vaccine construct was modeled via I-TASSER, and its interaction with Toll-like receptor 4 (TLR4) was evaluated using molecular docking and molecular dynamics simulation. C-ImmSim server was implemented to examine the immune response against the designed multi-epitope antigen.
The designed chimeric vaccine construct included 21 immunodominant epitopes (six B-cell, eight cytotoxic T lymphocyte, and seven helper T-lymphocyte) and is predicted non-allergen, antigenic, soluble, with suitable physicochemical features, that can promote cross-protection among the MPXV strains. The selected epitopes indicated a wide global population coverage (93.62%). Most finalized epitopes have 70%-100% sequence similarity with the experimentally validated immune epitopes of the vaccinia virus, which can be helpful in the speedy progression of vaccine design. Lastly, molecular docking and molecular dynamics simulation computed stable and energetically favourable interaction between the putative antigen and TLR4.
Our results show that the multi-epitope vaccine might elicit cellular and humoral immune responses and could be a potential vaccine candidate against the MPXV infection. Further experimental testing of the proposed vaccine is warranted to validate its safety and efficacy profile.
当前的猴痘（MPX）疫情由猴痘病毒（MPXV）引起，已成为全球关注的焦点，全球已有超过 59000 例感染病例和 23 例死亡。
本研究旨在利用强大的免疫信息学方法，针对 MPXV 的膜结合、包膜和细胞外蛋白，制定嵌合抗原。这种策略同样可以应用于鉴定其他导致慢性疾病的病原体的免疫优势表位，并设计针对这些病原体的多表位疫苗组合，这些病原体的慢性疾病难以干预。
采用反向疫苗学方法筛选出 11 种潜在的候选疫苗，然后对其进行筛选和映射，以预测免疫优势 B 细胞和 T 细胞表位。最终的表位通过合适的接头、佐剂（促复苏因子）、PADRE 序列（13 个氨基酸）和 HIV TAT 序列（11 个氨基酸）与融合，形成多价表位疫苗。使用生物信息学工具进行密码子适应性和计算克隆。通过 I-TASSER 对嵌合疫苗构建体的三级结构进行建模，并通过分子对接和分子动力学模拟评估其与 Toll 样受体 4（TLR4）的相互作用。使用 C-ImmSim 服务器评估针对设计的多表位抗原的免疫反应。
设计的嵌合疫苗构建体包括 21 个免疫优势表位（6 个 B 细胞、8 个细胞毒性 T 淋巴细胞和 7 个辅助 T 淋巴细胞），预测为非过敏原、抗原性、可溶性，具有合适的理化特性，可促进 MPXV 株之间的交叉保护。所选表位在全球范围内具有 93.62%的高覆盖率。大多数最终确定的表位与已验证的天花病毒免疫表位具有 70%-100%的序列相似性，这有助于快速推进疫苗设计。最后，分子对接和分子动力学模拟计算出假定抗原与 TLR4 之间稳定且能量有利的相互作用。
我们的结果表明，多表位疫苗可能引发细胞和体液免疫反应，是一种有潜力的 MPXV 感染疫苗候选物。需要进一步的实验测试来验证该疫苗的安全性和有效性。
