School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, UK B4 7ET.
Immunomedicine Group, Facultad de Medicina, Departamento de Inmunologia & O2, Universidad Complutense de Madrid, Madrid, Spain.
J Immunol Res. 2020 Mar 19;2020:7235742. doi: 10.1155/2020/7235742. eCollection 2020.
West Nile Virus (WNV) causes a debilitating and life-threatening neurological disease in humans. Since its emergence in Africa 50 years ago, new strains of WNV and an expanding geographical distribution have increased public health concerns. There are no licensed therapeutics against WNV, limiting effective infection control. Vaccines represent the most efficacious and efficient medical intervention known. Epitope-based vaccines against WNV remain significantly underexploited. Here, we use a selection protocol to identify a set of conserved prevalidated immunogenic T cell epitopes comprising a putative WNV vaccine. Experimentally validated immunogenic WNV epitopes and WNV sequences were retrieved from the IEDB and West Nile Virus Variation Database. Clustering and multiple sequence alignment identified a smaller subset of representative sequences. Protein variability analysis identified evolutionarily conserved sequences, which were used to select a diverse set of immunogenic candidate T cell epitopes. Cross-reactivity and human leukocyte antigen-binding affinities were assessed to eliminate unsuitable epitope candidates. Population protection coverage (PPC) quantified individual epitopes and epitope combinations against the world population. 3 CD8+ T cell epitopes (ITYTDVLRY, TLARGFPFV, and SYHDRRWCF) and 1 CD4+ epitope (VTVNPFVSVATANAKVLI) were selected as a putative WNV vaccine, with an estimated PPC of 97.14%.
西尼罗河病毒(WNV)会导致人类出现使人虚弱且危及生命的神经系统疾病。自 50 年前在非洲出现以来,WNV 的新毒株和不断扩大的地理分布范围增加了人们对公共卫生的担忧。目前还没有针对 WNV 的许可疗法,这限制了有效的感染控制。疫苗是目前已知最有效和最有效的医疗干预手段。针对 WNV 的表位疫苗仍然没有得到充分利用。在这里,我们使用一种选择方案来鉴定一组包含潜在 WNV 疫苗的保守的预先验证的免疫原性 T 细胞表位。从 IEDB 和西尼罗河病毒变异数据库中检索了经过实验验证的免疫原性 WNV 表位和 WNV 序列。聚类和多序列比对确定了较小的代表性序列子集。蛋白质变异分析确定了进化上保守的序列,这些序列被用于选择多样化的免疫原性候选 T 细胞表位。评估了交叉反应性和人类白细胞抗原结合亲和力,以消除不合适的表位候选物。人群保护覆盖率 (PPC) 量化了针对世界人口的个体表位和表位组合。选择了 3 个 CD8+ T 细胞表位(ITYTDVLRY、TLARGFPFV 和 SYHDRRWCF)和 1 个 CD4+表位(VTVNPFVSVATANAKVLI)作为潜在的 WNV 疫苗,估计的 PPC 为 97.14%。