Rai Jade, Lok Ka In, Mok Chun Yin, Mann Harvinder, Noor Mohammed, Patel Pritesh, Flower Darren R
Aston Pharmacy School, Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK.
Bioinformation. 2012;8(6):272-5. doi: 10.6026/97320630008272. Epub 2012 Mar 31.
Epitope prediction is becoming a key tool for vaccine discovery. Prospective analysis of bacterial and viral genomes can identify antigenic epitopes encoded within individual genes that may act as effective vaccines against specific pathogens. Since B-cell epitope prediction remains unreliable, we concentrate on T-cell epitopes, peptides which bind with high affinity to Major Histacompatibility Complexes (MHC). In this report, we evaluate the veracity of identified T-cell epitope ensembles, as generated by a cascade of predictive algorithms (SignalP, Vaxijen, MHCPred, IDEB, EpiJen), as a candidate vaccine against the model pathogen uropathogenic gram negative bacteria Escherichia coli (E-coli) strain 536 (O6:K15:H31). An immunoinformatic approach was used to identify 23 epitopes within the E-coli proteome. These epitopes constitute the most promiscuous antigenic sequences that bind across more than one HLA allele with high affinity (IC50 < 50nM). The reliability of software programmes used, polymorphic nature of genes encoding MHC and what this means for population coverage of this potential vaccine are discussed.
表位预测正成为疫苗研发的关键工具。对细菌和病毒基因组进行前瞻性分析,能够识别单个基因中编码的抗原表位,这些表位可能作为针对特定病原体的有效疫苗。由于B细胞表位预测仍然不可靠,我们专注于T细胞表位,即与主要组织相容性复合体(MHC)具有高亲和力结合的肽段。在本报告中,我们评估了由一系列预测算法(SignalP、Vaxijen、MHCPred、IDEB、EpiJen)生成的已识别T细胞表位组合作为针对模型病原体尿路致病性革兰氏阴性菌大肠杆菌(E-coli)菌株536(O6:K15:H31)的候选疫苗的准确性。采用免疫信息学方法在大肠杆菌蛋白质组中鉴定出23个表位。这些表位构成了最具多反应性的抗原序列,它们以高亲和力(IC50 < 50nM)与多个HLA等位基因结合。文中讨论了所使用软件程序的可靠性、编码MHC的基因的多态性以及这对这种潜在疫苗的人群覆盖率意味着什么。