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An Approach for a Synthetic CTL Vaccine Design against Zika Flavivirus Using Class I and Class II Epitopes Identified by Computer Modeling

机译：使用计算机建模识别的I类和II类表位针对寨卡黄病毒合成CTL疫苗设计的方法

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The threat posed by severe congenital abnormalities related to Zika virus (ZKV) infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL) response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL) vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift. Because naturally processed and presented human ZKV T cell epitopes have not yet been described, we identified predicted class I peptide sequences on ZKV matching previously identified DNV (Dengue) class I epitopes and by using a Major Histocompatibility Complex (MHC) binding prediction tool. A subset of those met the criteria for optimal CD8+ attack based on physical chemistry parameters determined by analysis of the ZKV protein structure encoded in open source Protein Data File (PDB) format files. We also identified candidate ZKV epitopes predicted to bind promiscuously to multiple HLA class II molecules that could provide help to the CTL responses. This work suggests that a CTL vaccine for ZKV may be possible even if ZKV exhibits significant antigenic drift. We have previously described a microsphere-based CTL vaccine platform capable of eliciting an immune response for class I epitopes in mice and are currently working toward in vivo testing of class I and class II epitope delivery directed against ZKV epitopes using the same microsphere-based vaccine.
机译：与寨卡病毒（ZKV）感染有关的严重先天性异常所造成的威胁使ZKV疫苗的开发变成了紧急情况。最近的工作表明对感染的细胞毒性T淋巴细胞（CTL）反应是对ZKV的重要防御机制。在这里，我们为开发用于ZKV黄病毒感染的细胞毒性T淋巴细胞（CTL）疫苗的新方法开发了原理和策略。提议的方法基于最近的研究，该研究使用蛋白质结构计算机模型进行HIV表位选择，该模型设计用于选择针对表现出抗原漂移的病毒优化的CTL攻击表位。因为尚未描述天然加工并呈递的人ZKV T细胞表位，所以我们通过使用主要组织相容性复合体（MHC）结合预测工具，在与先前确定的DNV（登革热）I类表位匹配的ZKV上确定了预测的I类肽序列。其中一个子集满足了基于最佳化学CD8 +攻击的标准，该物理化学参数是通过分析开源蛋白质数据文件（PDB）格式文件中编码的ZKV蛋白质结构而确定的。我们还确定了候选ZKV表位，这些表位预计会与多个HLA II类分子混杂结合，从而可以帮助CTL反应。这项工作表明，即使ZKV表现出明显的抗原漂移，也可以使用ZTL的CTL疫苗。我们之前已经描述了一种基于微球的CTL疫苗平台，该平台能够引发小鼠中I类表位的免疫反应，目前正在努力使用相同的基于微球的疫苗进行针对ZKV表位的I类和II类表位递送的体内测试。

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