Dehghankhold Mahvash, Nezafat Navid, Farahmandnejad Mitra, Abolmaali Samira Sadat, Tamaddon Ali Mohammad
Department of Pharmaceutical Nanotechnology, Shiraz University of Medical Sciences, Shiraz, Iran.
Pharmaceutical Sciences Research Center, Shiraz University of Medical Science, Shiraz, Iran.
Biotechnol Appl Biochem. 2025 Feb;72(1):164-186. doi: 10.1002/bab.2654. Epub 2024 Sep 8.
Melanoma is known to be the most hazardous and life-threatening type of skin cancer. Although numerous treatments have been authorized in recent years, they often result in severe side effects and may not fully cure the disease. To combat this issue, immunotherapy has emerged as a promising approach for the prevention and treatment of melanoma. Specifically, the use of epitope melanoma vaccine, a subset of immunotherapy, has recently gained attention. The aim of this study was to create a multi-epitope melanoma vaccine using immunoinformatic methods. Two well-known antigens, NYESO-1 and MAGE-C2, were selected due to their strong immunogenicity and high expression in melanoma. To enhance the immunogenicity of the peptide vaccine, Brucella cell-surface protein 31 (BCSP31), the G5 domain of resuscitation-promoting factor B (RpfB) adjuvants, and the helper epitope of pan HLADR-binding epitope (PADRE) were incorporated to vaccine construct. These different segments were connected with suitable linkers and the resulting vaccine structure was evaluated for its physicochemical, structural, and immunological properties using computational tools. The designed vaccine was found to have satisfactory allergenicity, antigenicity, and physicochemical parameters. Additionally, a high-quality tertiary structure of the vaccine was achieved through modeling, refinement, and validation. Docking and molecular dynamics studies showed that the vaccine had a stable and appropriate interaction with the cognate TLR2 and TLR4 receptors during the simulation period. Finally, in silico immune simulation analysis revealed a significant increase in the levels of helper and cytotoxic T cells, as well as the cytokines interferon-gamma and interleukin-2, after repeated exposure to the melanoma vaccine. These results suggest that the designed vaccine has the potential to be an effective therapeutic option for melanoma. However, additional in vitro and in vivo validations are crucial to assess real-world efficacy and safety.
黑色素瘤是已知最具危害性和威胁生命的皮肤癌类型。尽管近年来已批准了多种治疗方法，但它们常常会导致严重的副作用，且可能无法完全治愈该疾病。为解决这一问题，免疫疗法已成为预防和治疗黑色素瘤的一种有前景的方法。具体而言，表位黑色素瘤疫苗作为免疫疗法的一个子集，最近受到了关注。本研究的目的是利用免疫信息学方法创建一种多表位黑色素瘤疫苗。由于NYESO-1和MAGE-C2这两种著名抗原具有强免疫原性且在黑色素瘤中高表达，因此被选作疫苗抗原。为增强肽疫苗的免疫原性，将布鲁氏菌细胞表面蛋白31（BCSP31）、复苏促进因子B（RpfB）佐剂的G5结构域以及泛HLADR结合表位（PADRE）的辅助表位整合到疫苗构建体中。这些不同的片段通过合适的连接子连接，然后使用计算工具评估所得疫苗结构的物理化学、结构和免疫学特性。结果发现，所设计的疫苗具有令人满意的致敏性、抗原性和物理化学参数。此外，通过建模、优化和验证获得了该疫苗高质量的三级结构。对接和分子动力学研究表明，在模拟期间，该疫苗与同源的TLR2和TLR4受体具有稳定且合适的相互作用。最后，计算机免疫模拟分析显示，在反复接触黑色素瘤疫苗后，辅助性T细胞和细胞毒性T细胞水平以及细胞因子γ干扰素和白细胞介素-2水平显著升高。这些结果表明，所设计的疫苗有可能成为黑色素瘤的一种有效治疗选择。然而，额外的体外和体内验证对于评估实际疗效和安全性至关重要。
