PDF(Pubmed)
Abstract：
Toxoplasmosis is a zoonotic disease caused by the protozoan parasite, Toxoplasma gondii known to infect almost all animals, including birds and humans globally. This disease has impacted the livestock industry and public health, where infection of domestic animals increases the zoonotic risk of transmission of infection to humans, threatening public health. Hence the need to discover novel and safe vaccines to fight against toxoplasmosis. In the current study, a novel multiepitope vaccine was designed using immunoinformatics techniques targeting T. gondii AMA1, GRA7 and ROP16 antigens, consisting of antigenic, immunogenic, non-allergenic and cytokine inducing T-cell (9 CD8+ and 15 CD4+) epitopes and four (4) B-cell epitopes fused together using AAY, KK and GPGPG linkers. The tertiary model of the proposed vaccine was predicted and validated to confirm the structural quality of the vaccine. The designed vaccine was highly antigenic (antigenicity = 0.6645), immunogenic (score = 2.89998), with molecular weight of 73.35 kDa, instability and aliphatic index of 28.70 and 64.10, respectively; and GRAVY of -0.363. The binding interaction, stability and flexibility were assessed with molecular docking and dynamics simulation, which revealed the proposed vaccine to have good structural interaction (binding affinity = -106.882 kcal/mol) and stability when docked with Toll like receptor-4 (TLR4). The results revealed that the Profilin-adjuvanted vaccine is promising, as it predicted induction of enhanced immune responses through the production of cytokines and antibodies critical in blocking host invasion.
摘要：
弓形虫病是由原生动物寄生虫引起的人畜共患疾病，已知弓形虫感染几乎所有动物，包括全球鸟类和人类。这种疾病影响了畜牧业和公共卫生，家畜的感染增加了人畜共患将感染传播给人类的风险，威胁公众健康。因此需要发现新的和安全的疫苗来对抗弓形虫病。在目前的研究中,使用免疫信息学技术设计了一种新型的多表位疫苗，靶向弓形虫AMA1，GRA7和ROP16抗原，由抗原性组成，免疫原性，使用AAY融合在一起的非变应原性和细胞因子诱导T细胞（9个CD8+和15个CD4+）表位和四（4）个B细胞表位，KK和GPGPG接头。预测并验证了所提出的疫苗的三级模型，以确认疫苗的结构质量。设计的疫苗具有高度抗原性（抗原性=0.6645），免疫原性（评分=2.89998），分子量为73.35kDa，不稳定性和脂肪族指数分别为28.70和64.10；Gravy为-0.363。结合相互作用，通过分子对接和动力学模拟评估稳定性和灵活性，这表明，当与Toll样受体4（TLR4）对接时，拟议的疫苗具有良好的结构相互作用（结合亲和力=-106.882kcal/mol）和稳定性。结果表明，Profilin佐剂疫苗是有前途的，因为它预测通过产生对阻断宿主入侵至关重要的细胞因子和抗体来诱导增强的免疫应答。
