以人副流感病毒 3 (HPIV-3) 稳定蛋白为目标的多肽疫苗 (MEBV) 的免疫形式学辅助合理设计。

IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal, genetic engineering & biotechnology Pub Date : 2023-12-06 DOI:10.1186/s43141-023-00623-5
Md Sakib Hossen, Md Nazmul Hasan, Munima Haque, Tawsif Al Arian, Sajal Kumar Halder, Md Jasim Uddin, M Abdullah-Al-Mamun, Md Salman Shakil
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摘要

背景:人副流感病毒(HPIV)是一种常见的 RNA 病毒,可引起呼吸道感染。人副流感病毒 3(HPIV-3)的致病性特别强,可导致严重的疾病,但目前还没有有效的疫苗或疗法:结果:本研究采用了一种系统的免疫形式学/反向疫苗学方法,通过分析病毒蛋白质组,设计了一种基于多表位的多肽疫苗来预防 HPIV-3。根据一系列治疗特征,我们选择了基质蛋白、血凝素神经氨酸酶和RNA引导的RNA聚合酶L这三种具有较大免疫学相关性的稳定抗原蛋白来预测和筛选合适的T细胞和B细胞表位。我们所需的所有表位均与人类蛋白质无同源性,具有较高的群体覆盖率(99.26%),并且在全球报告的 HPIV-3 分离物中具有较高的保守性。然后,所有的 T 细胞和 B 细胞表位都被假定配体连接起来,最终形成了一个 478 氨基酸长的构建体。经过计算完善、验证和彻底筛选,多个项目将我们的多肽疫苗评定为生物物理稳定、抗原性、过敏原和对人体无毒。疫苗蛋白与先天性免疫受体 TLR3、TLR4 和 TLR8 有足够稳定的相互作用和结合亲和力。此外,疫苗序列在 pET32a ( +) 载体中的密码子优化和虚拟克隆表明,它可以在细菌系统中轻松表达:硅学设计的 HPIV-3 疫苗在诱发有效免疫反应方面表现出了潜力。这项研究为疫苗的进一步临床前和临床评估铺平了道路,为未来抗击 HPIV-3 感染的解决方案带来了希望。
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Immunoinformatics-aided rational design of multiepitope-based peptide vaccine (MEBV) targeting human parainfluenza virus 3 (HPIV-3) stable proteins.

Background: Human parainfluenza viruses (HPIVs) are common RNA viruses responsible for respiratory tract infections. Human parainfluenza virus 3 (HPIV-3) is particularly pathogenic, causing severe illnesses with no effective vaccine or therapy available.

Results: The current study employed a systematic immunoinformatic/reverse vaccinology approach to design a multiple epitope-based peptide vaccine against HPIV-3 by analyzing the virus proteome. On the basis of a number of therapeutic features, all three stable and antigenic proteins with greater immunological relevance, namely matrix protein, hemagglutinin neuraminidase, and RNA-directed RNA polymerase L, were chosen for predicting and screening suitable T-cell and B-cell epitopes. All of our desired epitopes exhibited no homology with human proteins, greater population coverage (99.26%), and high conservancy among reported HPIV-3 isolates worldwide. All of the T- and B-cell epitopes are then joined by putative ligands, yielding a 478-amino acid-long final construct. Upon computational refinement, validation, and thorough screening, several programs rated our peptide vaccine as biophysically stable, antigenic, allergenic, and non-toxic in humans. The vaccine protein demonstrated sufficiently stable interaction as well as binding affinity with innate immune receptors TLR3, TLR4, and TLR8. Furthermore, codon optimization and virtual cloning of the vaccine sequence in a pET32a ( +) vector showed that it can be readily expressed in the bacterial system.

Conclusion: The in silico designed HPIV-3 vaccine demonstrated potential in evoking an effective immune response. This study paves the way for further preclinical and clinical evaluation of the vaccine, offering hope for a future solution to combat HPIV-3 infections.

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