ABSTRACT

Objective

Ascaris lumbricoides infects 80 million people per year, causing malnutrition, stunted growth of children etc., but there is no vaccine available against it. We aimed to design a multimeric-subunit vaccine using comprehensive immunoinformatic approach.

Research design and Methods

The T and B cell epitopes were shortlisted on antigenicity, allergenicity, and toxicity from proteome data and joined with appropriate linkers. The physical characteristics of vaccine candidate was calculated and docking/molecular dynamic simulation performed to validate its robustness. The multimeric protein was codon optimized and in-silico cloned in pET28b.

Results

From the 23,604 proteins of Ascaris, we filtered based on epitope prediction, localization, antigenicity, and allergenicity. Prepared a vaccine of 534 amino acid long, 56.31 kD weight and pI 4.52. Physiochemical features showed it is soluble, highly antigenic and non-allergenic. Its tertiary structure was forecasted, certified, and refined. The immunoinformatic simulation studies showed it to be potent T and B cell stimulator.

Conclusions

We identified highly antigenic peptides of Ascaris from its proteome with good potential to induce innate as well as humoral immune response. These peptides were used to design a chimeric vaccine against Ascariasis infection, which can be used for prophylactic purpose but needs experimental and clinical validation.

中文翻译：

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免疫信息学驱动利用其整个免疫原性表位构建针对蛔虫的多表位候选疫苗

摘要

客观的

蛔虫每年感染 8000 万人，导致营养不良、儿童发育迟缓等，但目前还没有针对它的疫苗。我们的目标是使用综合免疫信息学方法设计一种多聚体亚单位疫苗。

研究设计和方法

T 和 B 细胞表位根据蛋白质组数据的抗原性、过敏性和毒性入围，并与适当的接头连接。计算候选疫苗的物理特性并进行对接/分子动力学模拟以验证其稳健性。多聚体蛋白经过密码子优化并在 pET28b 中进行计算机克隆。

结果

从蛔虫的 23,604 种蛋白质中，我们根据表位预测、定位、抗原性和过敏原性进行过滤。制备了534个氨基酸长、56.31 kD重量和pI 4.52的疫苗。理化特征表明它是可溶性的、高抗原性和非过敏性的。对其三级结构进行了预测、认证和改进。免疫信息学模拟研究表明它是有效的 T 和 B 细胞刺激剂。

结论

我们从蛔虫的蛋白质组中鉴定出高度抗原性的肽，具有诱导先天和体液免疫反应的良好潜力。这些肽用于设计抗蛔虫感染的嵌合疫苗，可用于预防目的，但需要实验和临床验证。