Shams Morteza, Nourmohammadi Hassan, Majidiani Hamidreza, Shariatzadeh Seyyed Ali, Asghari Ali, Fatollahzadeh Mohammad, Irannejad Hamid
Zoonotic Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran.
Department of Internal Medicine, Shahid Mostafa Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran.
Biologia (Bratisl). 2022;77(1):277-289. doi: 10.1007/s11756-021-00934-3. Epub 2021 Nov 29.
Visceral leishmaniasis (VL) is a severe disease with particular endemicity in over 80 countries worldwide. There is no approved human vaccine against VL in the market. This study was aimed at designing and evaluation of a multimeric vaccine candidate against through utilization of helper T lymphocyte (HTL) and cytotoxic T lymphocyte (CTL) immunodominant proteins from histone H1, KMP11, LACK and LeIF antigens. Top-ranked mouse MHC-I, MHC-II binders and CTL epitopes were predicted and joined together via spacers. Also, a TLR-4 agonist (RS-09 synthetic protein) and His-tag were added to the N- and C-terminal of the vaccine sequence, respectively. The final chimeric vaccine had a length of 184 amino acids with a molecular weight of 18.99 kDa. Physico-chemical features showed a soluble, highly-antigenic and non-allergenic candidate. Secondary and tertiary structures were predicted, and subsequent analyses confirmed the construct stability that was capable to properly interact with TLR-4/MD2 receptor. Immunoinformatics simulation displayed potent stimulation of T cell immune responses, with particular rise in IFN-γ, upon vaccination with the proposed multi-epitope candidate. In conclusion, immunoinformatics data demonstrated a highly antigenic vaccine candidate in mouse, which could develop considerable levels clearance mechanisms and other components of cellular immune profile, and can be directed for VL prophylactic purposes.
The online version contains supplementary material available at 10.1007/s11756-021-00934-3.
内脏利什曼病（VL）是一种严重疾病，在全球80多个国家具有特定的地方性。目前市场上尚无获批的针对VL的人用疫苗。本研究旨在通过利用来自组蛋白H1、KMP11、LACK和LeIF抗原的辅助性T淋巴细胞（HTL）和细胞毒性T淋巴细胞（CTL）免疫显性蛋白，设计和评估一种针对VL的多聚体候选疫苗。预测了排名靠前的小鼠MHC-I、MHC-II结合物和CTL表位，并通过间隔序列将它们连接在一起。此外，分别在疫苗序列的N端和C端添加了TLR-4激动剂（RS-09合成蛋白）和His标签。最终的嵌合疫苗长度为184个氨基酸，分子量为18.99 kDa。物理化学特性表明该候选疫苗具有可溶性、高抗原性且无致敏性。预测了二级和三级结构，后续分析证实了该构建体的稳定性，其能够与TLR-4/MD2受体正确相互作用。免疫信息学模拟显示，接种所提出的多表位候选疫苗后，T细胞免疫反应受到有效刺激，尤其是IFN-γ水平显著升高。总之，免疫信息学数据表明在小鼠中该候选疫苗具有高抗原性，可引发相当水平的清除机制和细胞免疫谱的其他成分，可用于VL的预防目的。
在线版本包含可在10.1007/s11756-021-00934-3获取的补充材料。
