Noor Fatima, Shahid Samiah, Fatima Muskan, Haider Syed Zeeshan, Al Shehri Zafer Saad, Alshehri Faez Falah, Rehman Abdur
Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, 35000, Pakistan.
Research Centre for Health Sciences (RCHS), The University of Lahore, Lahore, 35000, Pakistan.
Mol Divers. 2025 Jan 28. doi: 10.1007/s11030-025-11108-7.
Melanoma, a highly aggressive skin cancer, remains a significant cause of mortality despite advancements in therapeutic strategies. There is an urgent demand for developing vaccines that can elicit strong and comprehensive immune responses against this malignancy. Achieving this goal is crucial to enhance the efficacy of immunological defense mechanisms in combating this disease. This research provides a thorough examination of the design, optimization, and validation of a multi-epitope vaccine (MEV) construct. Using computational and in silico methods, the study specifically targets key immune receptors including MHC-I, MHC-I, and TLR4. The MEV construct was codon-optimized and effectively cloned into the E. coli pET-28a(+) vector to improve expression efficiency. To assess the stability and flexibility of the vaccine constructs in complex with their target receptors, molecular dynamics (MD) simulations were performed. The findings showed that the MHC-I-MEV complex demonstrated the greatest stability, with the MHC-II-MEV and TLR4-MEV complexes following instability. Immune simulation analyses revealed robust immune responses, evidenced by significant antibody production and the activation of cell mediated immune responses. These results highlight the MEV construct's potential as a versatile vaccine candidate, capable of eliciting strong and diverse immune responses. The integration of structural and energetic analyses, combined with immune simulation, provides a solid foundation for further experimental validation and therapeutic development.
黑色素瘤是一种侵袭性很强的皮肤癌，尽管治疗策略有所进步，但它仍然是导致死亡的一个重要原因。迫切需要开发能够引发针对这种恶性肿瘤的强大而全面免疫反应的疫苗。实现这一目标对于提高免疫防御机制对抗这种疾病的效力至关重要。本研究对一种多表位疫苗（MEV）构建体的设计、优化和验证进行了全面检查。该研究使用计算和计算机模拟方法，特别针对包括MHC-I、MHC-II和TLR4在内的关键免疫受体。MEV构建体经过密码子优化，并有效地克隆到大肠杆菌pET-28a(+)载体中以提高表达效率。为了评估疫苗构建体与其靶受体结合时的稳定性和灵活性，进行了分子动力学（MD）模拟。结果表明，MHC-I-MEV复合物表现出最大的稳定性，MHC-II-MEV和TLR4-MEV复合物次之。免疫模拟分析显示出强大的免疫反应，表现为显著的抗体产生和细胞介导免疫反应的激活。这些结果突出了MEV构建体作为一种通用疫苗候选物的潜力，能够引发强大而多样的免疫反应。结构和能量分析与免疫模拟的结合，为进一步的实验验证和治疗开发提供了坚实的基础。
