Gupta Sakshi, Desai Drashti, Patel Mansi, Jyotishi Charmi, Saleh Ahmad Mahmoud, Gupta Reeshu
Parul Institute of Applied Sciences, Parul University, Vadodara, India.
Centre of Research for Development, Parul University, Vadodara, India.
Asian Pac J Cancer Prev. 2025 Jan 1;26(1):327-338. doi: 10.31557/APJCP.2025.26.1.327.
Breast cancer remains a significant global health challenge, requiring innovative therapeutic strategies. In silico methods, which leverage computational tools, offer a promising pathway for vaccine development. These methods facilitate antigen identification, epitope prediction, immune response modelling, and vaccine optimization, accelerating the design process.
This study employed a reverse vaccinology approach combined with various bioinformatic tools to design a multi-epitope peptide vaccine.
Using reverse vaccinology, AKT1 and PARP1 were identified as potential vaccine candidates, as their expression levels were significantly higher in breast cancer samples compared to healthy controls. The vaccine was designed by integrating immune cell epitopes with a TLR4 agonist as an adjuvant. It demonstrated high antigenicity, no allergenicity, and no toxicity. Validation of its 3D structure using the Ramachandran plot confirmed optimal conformation and stereochemical properties. Molecular docking and simulation studies showed the vaccine was stable and compact when interacting with TLR4. Moreover, the subunit vaccine effectively eliminated the antigen and triggered a strong IgG/IgM immune response lasting approximately one year (350 days).
These findings suggest that the designed vaccine holds promise as a therapeutic option for breast cancer. However, further in vitro and in vivo studies are necessary to validate its efficacy before advancing to clinical trials.
乳腺癌仍然是一项重大的全球健康挑战,需要创新的治疗策略。利用计算工具的计算机模拟方法为疫苗开发提供了一条有前景的途径。这些方法有助于抗原识别、表位预测、免疫反应建模和疫苗优化,加速设计过程。
本研究采用反向疫苗学方法结合各种生物信息学工具设计一种多表位肽疫苗。
通过反向疫苗学,AKT1和PARP1被确定为潜在的疫苗候选物,因为与健康对照相比,它们在乳腺癌样本中的表达水平显著更高。该疫苗通过将免疫细胞表位与作为佐剂的TLR4激动剂整合而设计。它表现出高抗原性、无致敏性且无毒性。使用拉氏图对其三维结构进行验证,证实了其最佳构象和立体化学性质。分子对接和模拟研究表明,该疫苗与TLR4相互作用时稳定且紧密。此外,亚单位疫苗有效清除了抗原,并引发了持续约一年(350天)的强烈IgG/IgM免疫反应。
这些发现表明,所设计的疫苗有望成为乳腺癌的一种治疗选择。然而,在推进到临床试验之前,需要进一步进行体外和体内研究以验证其疗效。