Mashhadi Abolghasem Shirazi Maryam, Hanan Mina, Arashkia Arash, Sadat Seyed Mehdi
Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran.
Department of Hepatitis, AIDS and Blood borne Diseases, Pasteur Institute of Iran, No: 69, Pasteur Ave, Hepatitis, Tehran, Iran.
Sci Rep. 2025 Sep 25;15(1):32809. doi: 10.1038/s41598-025-17196-7.
A key characteristic of HIV-1 persistence under antiretroviral therapy is its ability to form a latent reservoir in T cells, creating an obstacle to the virus eradication, therefore, there is no effective and permanent treatment against HIV-1. This study aims to develop an epitope-based vaccine that targets HIV-1's key CTL epitopes involved in infection and latency. After studying and carefully checking previous reports and immunoinformatics, a multi-epitope vaccine was designed with strong CTL (Gag p24 and Pol) epitopes. CPP peptide (Tat) and an adjuvant (β-defensin) were incorporated into the vaccine construct for cell entry and to improve immunogenicity. The designed vaccine was evaluated in terms of antigenicity, allergenicity, safety, various physicochemical properties, solubility, and molecular docking with TLR4 using in silico tools. Immune simulation predicted a significant induction of immune responses. Successful expression and purification of the recombinant protein in E. coli BL21 strain, followed by confirmation by Western blot, demonstrated the feasibility of the vaccine production. Finally, our findings suggest that the designed epitope-based vaccine can induce humoral and cellular immune responses and is a suitable candidate for an HIV-1 therapeutic vaccine to control infection and latency.
抗逆转录病毒疗法下HIV-1持续存在的一个关键特征是其在T细胞中形成潜伏库的能力,这给病毒根除带来了障碍,因此,目前尚无针对HIV-1的有效且永久性治疗方法。本研究旨在开发一种基于表位的疫苗,该疫苗靶向参与感染和潜伏的HIV-1关键CTL表位。在研究并仔细核对先前的报告和免疫信息学之后,设计了一种具有强CTL(Gag p24和Pol)表位的多表位疫苗。将CPP肽(Tat)和一种佐剂(β-防御素)纳入疫苗构建体,以实现细胞进入并提高免疫原性。使用计算机工具从抗原性、致敏性、安全性、各种物理化学性质、溶解性以及与TLR4的分子对接等方面对设计的疫苗进行了评估。免疫模拟预测该疫苗能显著诱导免疫反应。在大肠杆菌BL21菌株中成功表达并纯化了重组蛋白,随后通过蛋白质印迹法进行确认,证明了疫苗生产的可行性。最后,我们的研究结果表明,设计的基于表位的疫苗可诱导体液免疫和细胞免疫反应,是控制HIV-1感染和潜伏的治疗性疫苗的合适候选者。