PDF(Pubmed)
Abstract：
Heat shock proteins (HSPs) improve cross-presentation of linked tumor antigens, thus they can be exploited in therapeutic vaccine design. Herein, in silico analyses of different vaccine constructs were performed based on human papillomavirus (HPV)-16 E7 protein linked to Homo sapiens/Mus musculus Hsp27 or Hsp70 in multiepitope and whole sequence forms. Then, computational comparison between different orientations of Hsp/E7 was carried out in both forms. Finally, molecular docking was performed between the designed constructs and signaling (TLRs) or endocytic (CD14, LOX-1 and SREC-1) receptors. Our data represented the high-ranked T-cell epitopes and the potential B-cell epitopes of Homo sapiens/Mus musculus Hsp27 and Hsp70. Moreover, molecular docking showed that whole sequence of Hsp27 had better interaction with all receptors than whole sequence of Hsp70 suggesting likely stronger stimulation of innate and adaptive immunity. All designed Homo sapiens/Mus musculus Hsp27/E7 constructs had better docking scores with the endocytic receptors especially SREC-1 than all designed Homo sapiens/Mus musculus Hsp70/E7 constructs in both orientations. Generally, the multiepitope-/whole sequence-based Homo sapiens/Mus musculus Hsp27-E7 fusion constructs showed more conservancy and immunogenicity than other designed constructs. These fusion constructs were non-allergenic, non-toxic and stable suggesting them as promising vaccine candidates against HPV-related cancers.
摘要：
热休克蛋白（HSPs）改善了相关肿瘤抗原的交叉呈递，因此，它们可以用于治疗性疫苗设计。在这里，基于以多表位和全序列形式与智人/小家鼠Hsp27或Hsp70连接的人乳头瘤病毒(HPV)-16E7蛋白,对不同疫苗构建体进行了计算机模拟分析.然后，两种形式的Hsp/E7不同取向之间的计算比较。最后,在设计的构建体和信号传导(TLRs)或内吞(CD14,LOX-1和SREC-1)受体之间进行分子对接。我们的数据代表了智人/小家鼠Hsp27和Hsp70的高级T细胞表位和潜在的B细胞表位。此外，分子对接显示Hsp27的整个序列与所有受体的相互作用比Hsp70的整个序列更好，这表明可能对先天和适应性免疫有更强的刺激。在两个方向上，所有设计的智人/小家鼠Hsp27/E7构建体都比所有设计的智人/小家鼠Hsp70/E7构建体与内吞受体尤其是SREC-1具有更好的对接得分。一般来说,基于多表位/全序列的智人/小家鼠Hsp27-E7融合构建体比其他设计的构建体显示出更高的稳定性和免疫原性。这些融合构建体是非过敏的，无毒且稳定，表明它们是针对HPV相关癌症的有希望的候选疫苗。
