Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
PLoS One. 2022 Nov 21;17(11):e0277751. doi: 10.1371/journal.pone.0277751. eCollection 2022.
Paratuberculosis is debilitating chronic enteritis usually characterized by diarrhea, decreased milk production, and progressive cachexia. Mycobacterium avium subspecies paratuberculosis (MAP) causes significant economic losses by affecting dairy herds globally. Development of protective vaccines is considered as one of the most effective controlling measures for MAP infections. In the current study, hydrophilic parts of MAP2191 and FAP-P proteins as two vaccine candidates were analyzed using immunoinformatics approaches.
After selecting the most hydrophilic parts of MAP2191 and FAP-P, helper and cytotoxic T-cell epitopes of ht-MAP2191 and ht-FAP-P were identified. The immunogenic, toxicity and physicochemical properties were assessed. Secondary structures of these proteins were predicted, and their tertiary structures were modeled, refined, and validated. Linear and conformational epitopes of corresponding B-cells were recognized. Then ht-MAP2191 and ht-FAP-P epitopes were employed for molecular docking simulations.
The results indicated that ht-MAP2191 and ht-FAP-P were immunogenic, non-allergenic, and non-toxic and possess potent T-cell and B-cell epitopes. Eventually, these protein constructs were docked favorably against TLR4.
According to the findings, ht-MAP2191 and ht-FAP-P could be effective protein-based vaccine candidates for paratuberculosis. It should be noted that to examine their efficacy, further in vitro and in vivo experiments are underway.
副结核病是一种衰弱的慢性肠炎，通常以腹泻、产奶量减少和进行性消瘦为特征。禽分枝杆菌亚种副结核分枝杆菌（MAP）通过影响全球奶牛群，造成了重大的经济损失。开发保护性疫苗被认为是控制 MAP 感染的最有效措施之一。在本研究中，使用免疫信息学方法分析了 MAP2191 和 FAP-P 蛋白的亲水性部分作为两种候选疫苗。
在选择了 MAP2191 和 FAP-P 的最亲水部分后，鉴定了 ht-MAP2191 和 ht-FAP-P 的辅助和细胞毒性 T 细胞表位。评估了它们的免疫原性、毒性和物理化学性质。预测了这些蛋白质的二级结构，并对它们的三级结构进行建模、细化和验证。识别了相应 B 细胞的线性和构象表位。然后，对 ht-MAP2191 和 ht-FAP-P 表位进行了分子对接模拟。
结果表明，ht-MAP2191 和 ht-FAP-P 具有免疫原性、非变应原性和非毒性，并且具有有效的 T 细胞和 B 细胞表位。最终，这些蛋白质结构被有利地对接 TLR4。
根据研究结果，ht-MAP2191 和 ht-FAP-P 可能是副结核病的有效基于蛋白质的候选疫苗。值得注意的是，为了检验它们的功效，正在进行进一步的体外和体内实验。
