Shams Morteza, Heydaryan Saeed, Bashi Mehdi Cheraghchi, Gorgani Bahman Noroozi, Ghasemi Ezatollah, Majidiani Hamidreza, Nazari Naser, Irannejad Hamid
Zoonotic Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran.
Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
In Silico Pharmacol. 2023 Mar 20;11(1):5. doi: 10.1007/s40203-023-00140-w. eCollection 2023.
Human toxoplasmosis is a global public health concern and a commercial vaccine is still lacking. The present in silico study was done to design a novel vaccine candidate using tachyzoite-specific SAG1-realted sequence (SRS) proteins. Overlapping B-cell and strictly-chosen human MHC-I binding epitopes were predicted and connected together using appropriate spacers. Moreover, a TLR4 agonist, human high mobility group box protein 1 (HMGB1), and His-tag were added to the N- and C-terminus of the vaccine sequence. The final vaccine had 442 residues and a molecular weight of 47.71 kDa. Physico-chemical evaluation showed a soluble, highly antigenic and non-allergen protein, with coils and helices as secondary structures. The vaccine 3D model was predicted by ITASSER server, subsequently refined and was shown to possess significant interactions with human TLR4. As well, potent stimulation of cellular and humoral immunity was demonstrated upon chimeric vaccine injection. Finally, the outputs showed that this vaccine model possesses top antigenicity, which could provoke significant cell-mediated immune profile including IFN-, and can be utilized towards prophylactic purposes.
The online version contains supplementary material available at 10.1007/s40203-023-00140-w.
人类弓形虫病是一个全球公共卫生问题,目前仍缺乏商业化疫苗。本计算机模拟研究旨在利用速殖子特异性SAG1相关序列(SRS)蛋白设计一种新型候选疫苗。预测了重叠的B细胞表位和严格筛选的人类MHC-I结合表位,并使用合适的间隔序列将它们连接在一起。此外,在疫苗序列的N端和C端添加了一种TLR4激动剂、人类高迁移率族蛋白1(HMGB1)和His标签。最终疫苗含有442个氨基酸残基,分子量为47.71 kDa。理化性质评估表明,该蛋白具有可溶性、高抗原性且无过敏原,其二级结构为卷曲和螺旋。疫苗的三维模型由ITASSER服务器预测,随后进行了优化,并显示与人类TLR4有显著相互作用。同样,注射嵌合疫苗后可有效刺激细胞免疫和体液免疫。最后,结果表明该疫苗模型具有极高的抗原性,可引发包括IFN-在内的显著细胞介导免疫反应,可用于预防目的。
在线版本包含可在10.1007/s40203-023-00140-w获取的补充材料。