Shehri Zafer Saad Al
Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Dawadmi, Saudi Arabia.
Front Immunol. 2025 Jul 8;16:1587224. doi: 10.3389/fimmu.2025.1587224. eCollection 2025.
INTRODUCTION: Esophageal cancer (EC) is a highly lethal malignancy characterized by the uncontrolled proliferation of cancerous cells within the esophagus. Despite recent advancements in therapeutic strategies, the prognosis remains poor, underscoring the urgent need for novel preventive and therapeutic approaches. Notably, several oncogenic viruses have been implicated in EC pathogenesis, prompting the exploration of epitope-based vaccines through immunoinformatics. METHODS: Using immunoinformatics and bioinformatics approaches, we designed a novel multi-epitope vaccine targeting viral agents associated with EC. Protein sequences of ten viral candidates were retrieved from the UniProt database and evaluated for antigenicity using the VaxiJen server. Five highly antigenic proteins derived from Human Cytomegalovirus (HCMV), Human Papillomavirus (HPV), Human Herpesvirus 8 (HHV-8), Human Immunodeficiency Virus (HIV), and Epstein-Barr Virus (EBV) were selected. T cell (CTL and HTL) and B cell (LBL) epitopes were predicted and screened for immunogenicity, allergenicity, and toxicity. The final vaccine construct incorporated β-defensin as an adjuvant and included 3 HTL, 8 CTL, and 8 LBL epitopes. Molecular docking and molecular dynamics (MD) simulations were conducted to assess the binding affinity of the vaccine with Toll-like receptor 3 (TLR3). In silico cloning was also performed using the pET-28a(+) vector in strain K12. RESULTS: The designed vaccine was found to be antigenic, non-allergenic, and non-toxic. Molecular docking revealed strong binding affinity between the vaccine construct and TLR3, which was further supported by MD simulation results indicating stable complex formation. Codon optimization and in silico cloning confirmed the high expression potential of the vaccine in the expression system. DISCUSSION: The in silico analyses suggest that the developed multi-epitope vaccine construct is a promising candidate for preventing EC associated with viral infections. While these findings are encouraging, further experimental validation through in vitro and in vivo studies is essential to confirm the vaccine's safety, immunogenicity, and protective efficacy.
引言：食管癌（EC）是一种具有高度致死性的恶性肿瘤，其特征在于食管内癌细胞的不受控制的增殖。尽管治疗策略最近有所进展，但预后仍然很差，这突出表明迫切需要新的预防和治疗方法。值得注意的是，几种致癌病毒与EC发病机制有关，这促使通过免疫信息学探索基于表位的疫苗。 方法：我们使用免疫信息学和生物信息学方法，设计了一种针对与EC相关的病毒因子的新型多表位疫苗。从UniProt数据库中检索了十种病毒候选物的蛋白质序列，并使用VaxiJen服务器评估其抗原性。选择了五种源自人巨细胞病毒（HCMV）、人乳头瘤病毒（HPV）、人疱疹病毒8（HHV-8）、人免疫缺陷病毒（HIV）和爱泼斯坦-巴尔病毒（EBV）的高抗原性蛋白质。预测并筛选了T细胞（CTL和HTL）和B细胞（LBL）表位的免疫原性、致敏性和毒性。最终的疫苗构建体包含β-防御素作为佐剂，并包括3个HTL、8个CTL和8个LBL表位。进行了分子对接和分子动力学（MD）模拟，以评估疫苗与Toll样受体3（TLR3）的结合亲和力。还使用pET-28a(+)载体在K12菌株中进行了电子克隆。 结果：发现设计的疫苗具有抗原性、无致敏性且无毒。分子对接显示疫苗构建体与TLR3之间具有强结合亲和力，MD模拟结果进一步支持了这一点，表明形成了稳定的复合物。密码子优化和电子克隆证实了疫苗在表达系统中的高表达潜力。 讨论：电子分析表明，开发的多表位疫苗构建体是预防与病毒感染相关的EC的有希望的候选物。虽然这些发现令人鼓舞，但通过体外和体内研究进行进一步的实验验证对于确认疫苗的安全性、免疫原性和保护效力至关重要。
Cancers (Basel). 2023-1-26
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