人副流感病毒广谱T细胞表位疫苗设计：一种免疫信息学方法

Designing a broad-spectrum multi-epitope vaccine against human parainfluenza virus: an immunoinformatics approach

摘要:

目的 人副流感病毒3型(human parainfluenza virus type 3, HPIV-3)是全球获得性呼吸道感染的关键致病因素，目前尚无特异性治疗药物。鉴于该病原体抗原具有复杂性和变异性，其疫苗开发进展较为滞后。设计具有广谱特性的新型疫苗，对于为持续突变的野生型毒株提供全面防护至关重要。方法 为克服病毒的抗原性变异，从NCBI下载不同的HPIV-3抗原蛋白(F、M、N和HN蛋白)序列，并通过序列比对分别生成共识序列，进一步运用反向疫苗学方法，预测并设计了一种针对HPIV-3的广谱T细胞表位疫苗。结果 该多表位疫苗包含来自F、M、N和HN蛋白的11个CTL表位(9-mer)和11个HTL表位(15-mer)，由355个氨基酸组成，不含佐剂。预测的T细胞表位具备可溶性、非致敏性、高抗原性及免疫原性。设计的疫苗能有效结合天然免疫中的Toll样受体，具有较好的稳定性和亲水性，且人口覆盖度较高。结论 本研究设计的HPIV-3多表位疫苗有望成为预防HPIV-3感染的候选疫苗，为疫苗的设计与开发提供了一种新颖的免疫信息学方法。

Abstract:

Objective Human parainfluenza virus type 3 (HPIV-3) is a key factor in global acquired respiratory infections, and there is no specific therapy available. Due to the complexity and variability of the pathogen antigen, the development of vaccines against HPIV-3 is lagging behind. It is crucial to design a novel broad-spectrum vaccine for comprehensive protection against continuously mutated wild-type strains.Methods To overcome the antigenic variation of the virus, we downloaded different HPIV-3 antigen proteins (F, M, N, and HN proteins) from NCBI and generated consensus sequences through sequence alignment. Furthermore, a broad-spectrum T cell epitope vaccine targeting HPIV-3 was predicted and designed via methods of reverse vaccinology.Results The multi-epitope vaccine (MEV) incorporated 11 cytotoxic T lymphocyte (CTL) epitopes (9-mer) and 11 helper T lymphocyte (HTL) epitopes (15-mer) from the F, M, N and HN proteins, being composed of 355 amino acid residues without adjuvant. The predicted T cell epitopes had solubility, no allergenicity, high antigenicity, and immunogenicity. The designed vaccine can effectively bind to Toll-like receptors in natural immunity, with good stability, hydrophilicity, and high population coverage.Conclusion The designed vaccine could be a candidate vaccine against HPIV-3 infection. We provide a novel immunoinformatics approach for vaccine design and development.