Multi-epitope DnaK peptide vaccine against S.Typhi: An in silico approach
Multi-epitope DnaK peptide vaccine against S.Typhi: An in silico approach
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DOI：
10.1016/j.vaccine.2018.05.106
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发表时间：
2018-06-27
期刊：
影响因子：
5.5
通讯作者：
Bansal, Anju
中科院分区：
文献类型：
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作者：
Verma, Shivani;Sugadev, Ragumani;Bansal, Anju
沙门氏菌是全球食源性和水源性肠道感染的主要原因之一，是全球特别是发展中国家显著发病率和死亡率的原因。目前可用的伤寒疫苗是中等有效的，有几个副作用，并不是有效的所有沙门氏菌血清型。由于这些疫苗的局限性和新出现的多药耐药性威胁，开发针对这些感染的有效疫苗日益成为优先事项。热休克蛋白（Hsps）是一种进化上保守的蛋白质，是宿主免疫反应中的优势抗原。本文是对S. Typhi DnaK和GroEL疫苗候选物对沙门氏菌和多种病原体非常有效，在本研究中，我们使用生物信息学方法设计了沙门氏菌多种血清型共有的多表位疫苗候选物。实施各种免疫信息学工具，如IEDB、EpiJen、BCPRED、ElliPro和VaxiJen，导致许多免疫原性B和T细胞表位的鉴定。利用ElliPro服务器生成DnaK的三维结构模型，预测B细胞构象表位。最有希望的T细胞表位（29个CTL，18个T辅助细胞）基于它们与常见的MHC等位基因的结合效率来选择。最后我们筛选出5个保护性抗原肽（PAP），它们包含高度保守的、抗原性和免疫原性的B /T细胞表位，与人类宿主同源性最低。通过变应原性预测工具（SORTALLER和AllerHunter）预测这些PAP为非变应原性。因此，这些免疫原性表位可用于预防或治疗用途，专门用于击败抗生素耐药性沙门氏菌。这些抗原首次被报道，它们的保守性也赋予它们作为针对其他多种病原体的潜在未来疫苗候选物。(C)2018爱思唯尔有限公司版权所有
Salmonella is one of the key global causes of food and water borne enteric infections, responsible for significant morbidity and mortality worldwide especially in developing countries. Currently available vaccines against typhoid are moderately effective with several side effects and not efficacious against all Salmonella serovars. Due to limitations of these vaccines and emerging threats of multidrug resistance, developing an effective vaccine against these infections has increasingly become a priority. Heat shock proteins (Hsps), being evolutionarily conserved, represent dominant antigens in the host immune response. In continuation of our earlier studies on the development of S. Typhi DnaK and GroEL vaccine candidates, highly efficacious against Salmonella and multiple pathogens, in the present study, we have designed multi-epitope vaccine candidates common to multiple serovars of Salmonella using bioinformatics approach. Implementing various immunoinformatics tools such as IEDB, EpiJen, BCPRED, ElliPro and VaxiJen, led to the identification of many immunogenic B and T cell epitopes. The 3-D structure model of DnaK was generated to predict conformational B-cell epitopes using ElliPro server. Most promising T cell epitopes (29 CTLs, 18 T-helper cells) were selected based on their binding efficiency with commonly occurring MHC alleles. Finally we narrowed down to 5 protective antigenic peptides (PAPs), comprising highly conserved, antigenic and immunogenic B /T cell epitopes, least homologous with human host. These PAPs were predicted to be non-allergenic by allergenicity prediction tools (SORTALLER and AllerHunter). Hence, these immunogenic epitopes can be used for prophylactic or therapeutic usages specifically to defeat antibiotic-resistant Salmonella. These antigens have been reported for the first time and their conserved nature endow them as potential future vaccine candidates against other multiple pathogens as well. (C) 2018 Elsevier Ltd. All rights reserved.