胰腺导管腺癌是最常见的胰腺癌，被认为是一个重大的全球健康问题。化疗和手术是目前胰腺癌治疗的支柱；但少数病例适合手术治疗，大多数病例会反复发作。与 DNA 或肽疫苗相比，用于胰腺癌的 mRNA 疫苗由于其递送、增强的免疫反应和较低的突变可能性而更有前景。我们通过分析 S100 家族蛋白构建了 mRNA 疫苗，这些蛋白都是晚期糖基化终产物受体的主要激活剂。我们应用了免疫信息学方法，包括理化性质分析、结构预测和验证、分子对接研究、计算机克隆和免疫模拟。设计的mRNA疫苗的分子量估计为165023.50 Da，并且具有高度可溶性（亲水性的总平均值为-0.440）。在结构评估中，疫苗似乎是一种稳定且功能良好的蛋白质（Z 得分为-8.94）。此外，对接分析表明该疫苗对 TLR-2 和 TLR-4 受体具有高亲和力。此外，“Vaccine-TLR-2”（-141.07 kcal/mol）和“Vaccine-TLR-4”（-271.72 kcal/mol）复合物的分子力学与广义玻恩和表面积溶剂化分析也表明强结合对受体的亲和力。密码子优化还提供了高表达水平，GC含量为47.04%，密码子适应指数得分为1.0。在一段时间内还观察到记忆 B 细胞和 T 细胞的出现，辅助 T 细胞和免疫球蛋白（IgM 和 IgG）水平增加。此外，预测mRNA疫苗的最小自由能为-1760.00 kcal/mol，表明疫苗在进入、转录和表达后的稳定性。这种假设的疫苗为胰腺癌的未来研究和治疗开发提供了突破性的工具。版权所有：© 2024 Masum 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Pancreatic ductal adenocarcinoma is the most prevalent pancreatic cancer, which is considered a significant global health concern. Chemotherapy and surgery are the mainstays of current pancreatic cancer treatments; however, a few cases are suitable for surgery, and most of the cases will experience recurrent episodes. Compared to DNA or peptide vaccines, mRNA vaccines for pancreatic cancer have more promise because of their delivery, enhanced immune responses, and lower proneness to mutation. We constructed an mRNA vaccine by analyzing S100 family proteins, which are all major activators of receptors for advanced glycation end products. We applied immunoinformatic approaches, including physicochemical properties analysis, structural prediction and validation, molecular docking study, in silico cloning, and immune simulations. The designed mRNA vaccine was estimated to have a molecular weight of 165023.50 Da and was highly soluble (grand average of hydropathicity of -0.440). In the structural assessment, the vaccine seemed to be a well-stable and functioning protein (Z score of -8.94). Also, the docking analysis suggested that the vaccine had a high affinity for TLR-2 and TLR-4 receptors. Additionally, the molecular mechanics with generalized Born and surface area solvation analysis of the "Vaccine-TLR-2" (-141.07 kcal/mol) and "Vaccine-TLR-4" (-271.72 kcal/mol) complexes also suggests a strong binding affinity for the receptors. Codon optimization also provided a high expression level with a GC content of 47.04% and a codon adaptation index score 1.0. The appearance of memory B-cells and T-cells was also observed over a while, with an increased level of helper T-cells and immunoglobulins (IgM and IgG). Moreover, the minimum free energy of the mRNA vaccine was predicted at -1760.00 kcal/mol, indicating the stability of the vaccine following its entry, transcription, and expression. This hypothetical vaccine offers a groundbreaking tool for future research and therapeutic development of pancreatic cancer.Copyright: © 2024 Masum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.