Department of Internal Medicine, Saint Louis University, Division of Infectious Diseases, Allergy, and Immunology, Saint Louis, MO, United States.
EpiVax, Inc., Providence, RI, United States.
Front Immunol. 2023 Aug 29;14:1247876. doi: 10.3389/fimmu.2023.1247876. eCollection 2023.
Zika virus (ZIKV) is a flavivirus primarily transmitted by species mosquitoes, first discovered in Africa in 1947, that disseminated through Southeast Asia and the Pacific Islands in the 2000s. The first ZIKV infections in the Americas were identified in 2014, and infections exploded through populations in Brazil and other countries in 2015/16. ZIKV infection during pregnancy can cause severe brain and eye defects in offspring, and infection in adults has been associated with higher risks of Guillain-Barré syndrome. We initiated a study to describe the natural history of Zika (the disease) and the immune response to infection, for which some results have been reported. In this paper, we identify ZIKV-specific CD4+ and CD8+ T cell epitopes that induce responses during infection. Two screening approaches were utilized: an untargeted approach with overlapping peptide arrays spanning the entire viral genome, and a targeted approach utilizing peptides predicted to bind human MHC molecules. Immunoinformatic tools were used to identify conserved MHC class I supertype binders and promiscuous class II binding peptide clusters predicted to bind 9 common class II alleles. T cell responses were evaluated in overnight IFN-γ ELISPOT assays. We found that MHC supertype binding predictions outperformed the bulk overlapping peptide approach. Diverse CD4+ T cell responses were observed in most ZIKV-infected participants, while responses to CD8+ T cell epitopes were more limited. Most individuals developed a robust T cell response against epitopes restricted to a single MHC class I supertype and only a single or few CD8+ T cell epitopes overall, suggesting a strong immunodominance phenomenon. Noteworthy is that many epitopes were commonly immunodominant across persons expressing the same class I supertype. Nearly all of the identified epitopes are unique to ZIKV and are not present in Dengue viruses. Collectively, we identified 31 immunogenic peptides restricted by the 6 major class I supertypes and 27 promiscuous class II epitopes. These sequences are highly relevant for design of T cell-targeted ZIKV vaccines and monitoring T cell responses to Zika virus infection and vaccination.
寨卡病毒（ZIKV）是一种黄病毒，主要通过 种蚊子传播，于 1947 年首次在非洲发现，随后在 21 世纪 00 年代传播到东南亚和太平洋岛屿。2014 年首次在美洲发现寨卡病毒感染，2015/16 年巴西和其他国家的人群中感染爆发。孕妇感染寨卡病毒可导致胎儿严重的脑和眼部缺陷，成人感染与吉兰-巴雷综合征的风险增加有关。我们开展了一项研究，以描述寨卡（疾病）的自然史和对感染的免疫反应，其中一些结果已经报告。在本文中，我们确定了诱导感染期间产生反应的寨卡病毒特异性 CD4+和 CD8+T 细胞表位。利用两种筛选方法：一种是覆盖整个病毒基因组的重叠肽阵列的无目标方法，另一种是利用预测与人类 MHC 分子结合的肽的有目标方法。免疫信息学工具用于识别保守的 MHC Ⅰ类超型结合物和预测与 9 种常见Ⅱ类等位基因结合的混杂Ⅱ类结合肽簇。通过 overnight IFN-γ ELISPOT 测定评估 T 细胞反应。我们发现，MHC 超型结合预测优于大量重叠肽方法。在大多数寨卡病毒感染的参与者中观察到多样化的 CD4+T 细胞反应，而 CD8+T 细胞表位的反应则更为有限。大多数人对单一 MHC Ⅰ类超型限制的表位产生了强大的 T 细胞反应，总体上只有一个或少数几个 CD8+T 细胞表位，表明存在强烈的免疫优势现象。值得注意的是，许多表位在表达相同 I 类超型的个体中普遍具有免疫优势。几乎所有鉴定的表位都是寨卡病毒特有的，而不是登革热病毒。总的来说，我们鉴定了 31 个受 6 种主要 I 类超型和 27 个混杂Ⅱ类表位限制的免疫原性肽。这些序列对于寨卡病毒疫苗的 T 细胞靶向设计以及监测寨卡病毒感染和疫苗接种的 T 细胞反应具有重要意义。
