Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Exp Parasitol. 2022 Aug;239:108295. doi: 10.1016/j.exppara.2022.108295. Epub 2022 Jun 14.
Visceral leishmaniasis (VL) remains a major public health problem across 98 countries. To date, VL has no effective drug. Vaccines, as the most successful breakthroughs in medicine, can promise an effective strategy to fight various diseases. More recently, self-assembled peptide nanoparticles (SAPNs) have attracted considerable attention in the field of vaccine design due to their multivalency. In this study, a SAPN nanovaccine was designed using various immunoinformatics methods. High-ranked epitopes were chosen from a number of antigens, including Leishmania-specific hypothetical protein (LiHy), Leishmania-specific antigenic protein (LSAP), histone H1, and sterol 24-c-methyltransferase (SMT). To facilitate the oligomerization process, pentameric and trimeric coiled-coil domains were employed. RpfE, a resuscitation-promoting factor of Mycobacterium tuberculosis, was added to induce strong immune responses. Pentameric and trimeric coiled-coil domains as well as eight immunodominant epitopes from antigenic proteins of Leishmania infantum, the causative agent of VL, were joined together using appropriate linkers. High-quality 3D structure of monomeric and oligomeric structures followed by refinement and validation processes demonstrated that the designed nanovaccine could be considered to be a promising medication against the parasite; however, experimental validation is essential to confirm the effectiveness of the nanovaccine.
内脏利什曼病（VL）仍然是 98 个国家的主要公共卫生问题。迄今为止，VL 尚无有效药物。疫苗作为医学上最成功的突破之一，可以承诺为抗击各种疾病提供有效的策略。最近，自组装肽纳米颗粒（SAPN）因其多价性而在疫苗设计领域引起了相当大的关注。在这项研究中，使用各种免疫信息学方法设计了 SAPN 纳米疫苗。从许多抗原中选择了排名较高的表位，包括利什曼原虫特异性假设蛋白（LiHy）、利什曼原虫特异性抗原蛋白（LSAP）、组蛋白 H1 和甾醇 24-c-甲基转移酶（SMT）。为了促进寡聚化过程，使用了五聚体和三聚体卷曲螺旋结构域。添加结核分枝杆菌的复苏促进因子 RpfE 以诱导强烈的免疫反应。使用适当的接头将五聚体和三聚体卷曲螺旋结构域以及来自内脏利什曼原虫（VL 的病原体）抗原蛋白的 8 个免疫优势表位连接在一起。单体和寡聚体结构的高质量 3D 结构以及精化和验证过程表明，设计的纳米疫苗可被视为一种有前途的寄生虫药物；然而，实验验证对于确认纳米疫苗的有效性至关重要。
