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一种针对 BK 病毒的通用治疗性疫苗设计的免疫信息学方法。

An immunoinformatic approach to universal therapeutic vaccine design against BK virus.

机构信息

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Creighton University School of Dentistry, Department of Oral Biology, Omaha, NE 68178, USA.

出版信息

Vaccine. 2019 Jun 6;37(26):3457-3463. doi: 10.1016/j.vaccine.2019.04.096. Epub 2019 May 13.

Abstract

In kidney transplant recipients (KTRs) long-term immunosuppression leads to BK virus (BKV) reactivation, with an increased incidence of BKV-associated pathologies and allograft rejection. The current approaches to limit BKV infection include a reduction in immunosuppression and use of anti-BKV drugs, which are clinically sub-optimal and lead to undesirable therapeutic outcomes. Here, we adopted an immune-based approach to augment the endogenous BKV specific T-cells. Using reverse vaccinology based in silico analyses, we designed a peptide-based multi-epitope vaccine for BKV (MVBKV). A major advantage of our approach is that the selected epitopes show an affinity towards all the 12 superfamilies of HLA class I alleles and 27 reference alleles of HLA class II. This suggests MVBKV's universal nature and its potential effectiveness in a wide-population base. To improve MVBKV's immunogenic properties, a synthetic Toll-like Receptor (TLR) 4 peptide ligand (RS09) was added to the final vaccine construct. The sequences of the individual epitopes were molecularly linked to form a 3D-stable synthetic protein. Overall, our immunoinformatic-based approach led to the design of a new MVBKV vaccine, which remains to be validated experimentally.

摘要

在肾移植受者(KTR)中,长期免疫抑制会导致 BK 病毒(BKV)重新激活,从而增加 BKV 相关病变和同种异体移植物排斥的发生率。目前限制 BKV 感染的方法包括减少免疫抑制和使用抗 BKV 药物,但这些方法在临床上并不理想,导致治疗效果不理想。在这里,我们采用了一种基于免疫的方法来增强内源性 BKV 特异性 T 细胞。我们使用基于反向疫苗学的计算机分析设计了一种用于 BKV(MVBKV)的基于肽的多表位疫苗。我们方法的一个主要优势是,所选表位对所有 12 个 HLA Ⅰ类等位基因超家族和 27 个 HLA Ⅱ类参考等位基因具有亲和力。这表明 MVBKV 具有普遍性,并且有可能在广泛的人群基础上发挥作用。为了提高 MVBKV 的免疫原性,在最终疫苗构建体中添加了一种合成的 Toll 样受体(TLR)4 肽配体(RS09)。各个表位的序列通过分子链接形成 3D 稳定的合成蛋白。总的来说,我们基于免疫信息学的方法导致了一种新的 MVBKV 疫苗的设计,该疫苗仍有待实验验证。

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