Reverse Vaccinology and Immunoinformatics Strategy to Screen Oncogenic Proteins and Development of a Multiepitope Peptide Vaccine Targeting Protein Kinases against Oral Cancer: An in-silico Study

利用反向疫苗学和免疫信息学策略筛选致癌蛋白并开发靶向蛋白激酶的多表位肽疫苗以对抗口腔癌:一项计算机模拟研究

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Abstract

BACKGROUND: Despite standard therapies and immunotherapies, the mortality rate of patients with oral cancer remains high. Therefore, there is a need for more effective and targeted treatments. Multi-epitope vaccines have been developed for various cancers owing to their easy protection and delivery. However, no multi-epitope vaccine has been designed to prevent oral cancer. METHODS: In this study, a reverse vaccinology approach, along with various machine-learning integrated immunoinformatics tools, was used to design a multi-epitope peptide vaccine. RESULTS: Using an integrated computational method, LYN Proto-Oncogene and AKT1 were identified as good candidates. Both LYN and AKT1 are protein kinases and plays a central role in regulating various outputs, such as proliferation, differentiation, apoptosis, and migration in cancer. These proteins were selected because of their favorable physicochemical properties, non-allergic, non-toxic, and antigenic nature. Suitable B and T cell epitopes were identified based on their physicochemical characteristics, toxicity, allergenicity, antigenicity, and immunogenicity. A vaccine was constructed using these immune epitopes and TLR4 agonist as an adjuvant. Molecular dynamics simulation suggests strong binding affinity for Toll-like receptor 4. Furthermore, immune simulation studies suggest the activation of immune cells and a strong IgG/IgM response for approximately one year. CONCLUSION: We propose that the vaccine developed has high immunogenic potential and able to induce both cell mediated and humoral immunity against oral cancer.

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