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一种与血激肽-1融合的基于异源亚型表位的抗流感病毒肽疫苗的设计。

Design of a heterosubtypic epitope-based peptide vaccine fused with hemokinin-1 against influenza viruses.

作者信息

Shahsavandi Shahla, Ebrahimi Mohammad Majid, Sadeghi Kaveh, Mahravani Homayoon

机构信息

Razi Vaccine & Serum Research Institute, Karaj, 31975, Iran,

出版信息

Virol Sin. 2015 Jun;30(3):200-7. doi: 10.1007/s12250-014-3504-0. Epub 2015 Apr 15.

Abstract

Influenza viruses continue to emerge and re-emerge, posing new threats for public health. Control and treatment of influenza depends mainly on vaccination and chemoprophylaxis with approved antiviral drugs. Identification of specific epitopes derived from influenza viruses has significantly advanced the development of epitope-based vaccines. Here, we explore the idea of using HLA binding data to design an epitope-based vaccine that can elicit heterosubtypic T-cell responses against circulating H7N9, H5N1, and H9N2 subtypes. The hemokinin-1 (HK-1) peptide sequence was used to induce immune responses against the influenza viruses. Five conserved high score cytotoxic T lymphocyte (CTL) epitopes restricted to HLA-A*0201-binding peptides within the hemagglutinin (HA) protein of the viruses were chosen, and two HA CTL/HK-1 chimera protein models designed. Using in silico analysis, which involves interferon epitope scanning, protein structure prediction, antigenic epitope determination, and model quality evaluation, chimeric proteins were designed. The applicability of one of these proteins as a heterosubtypic epitopebased vaccine candidate was analyzed.

摘要

流感病毒不断出现和再次出现,对公共卫生构成新的威胁。流感的控制和治疗主要依赖于接种疫苗以及使用经批准的抗病毒药物进行化学预防。对源自流感病毒的特定表位的鉴定显著推动了基于表位的疫苗的开发。在此,我们探讨利用HLA结合数据来设计一种基于表位的疫苗的想法,该疫苗能够引发针对流行的H7N9、H5N1和H9N2亚型的异源亚型T细胞应答。使用血激肽-1(HK-1)肽序列来诱导针对流感病毒的免疫应答。选择了五种保守的高分细胞毒性T淋巴细胞(CTL)表位,这些表位局限于病毒血凝素(HA)蛋白内与HLA-A*0201结合的肽段,并设计了两种HA CTL/HK-1嵌合蛋白模型。利用计算机分析,包括干扰素表位扫描、蛋白质结构预测、抗原表位测定和模型质量评估,设计了嵌合蛋白。分析了其中一种蛋白作为异源亚型基于表位的疫苗候选物的适用性。

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