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