新冠病毒刺突蛋白疫苗诱导的 T 细胞反应的克隆结构和特异性。
Clonal structure and the specificity of vaccine-induced T cell response to SARS-CoV-2 Spike protein.
机构信息
Laboratory of Transplantation Immunology, National Medical Research Center for Hematology, Moscow, Russia.
Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
出版信息
Front Immunol. 2024 Apr 2;15:1369436. doi: 10.3389/fimmu.2024.1369436. eCollection 2024.
Adenovirus vaccines, particularly the COVID-19 Ad5-nCoV adenovirus vaccine, have emerged as promising tools in the fight against infectious diseases. In this study, we investigated the structure of the T cell response to the Spike protein of the SARS-CoV-2 virus used in the COVID-19 Ad5-nCoV adenoviral vaccine in a phase 3 clinical trial (NCT04540419). In 69 participants, we collected peripheral blood samples at four time points after vaccination or placebo injection. Sequencing of T cell receptor repertoires from Spike-stimulated T cell cultures at day 14 from 17 vaccinated revealed a more diverse CD4 T cell repertoire compared to CD8. Nevertheless, CD8 clonotypes accounted for more than half of the Spike-specific repertoire. Our longitudinal analysis showed a peak T cell response at day 14, followed by a decline until month 6. Remarkably, multiple T cell clonotypes persisted for at least 6 months after vaccination, as demonstrated by ex vivo stimulation. Examination of CDR3 regions revealed homologous sequences in both CD4 and CD8 clonotypes, with major CD8 clonotypes sharing high similarity with annotated sequences specific for the NYNYLYRLF peptide, suggesting potential immunodominance. In conclusion, our study demonstrates the immunogenicity of the Ad5-nCoV adenoviral vaccine and highlights its ability to induce robust and durable T cell responses. These findings provide valuable insight into the efficacy of the vaccine against COVID-19 and provide critical information for ongoing efforts to control infectious diseases.
腺病毒疫苗,特别是 COVID-19 Ad5-nCoV 腺病毒疫苗,已成为对抗传染病的有前途的工具。在这项 3 期临床试验(NCT04540419)中,我们研究了 COVID-19 Ad5-nCoV 腺病毒疫苗中使用的 SARS-CoV-2 病毒 Spike 蛋白的 T 细胞反应结构。在 69 名参与者中,我们在接种疫苗或安慰剂注射后四个时间点收集外周血样本。从 17 名接种疫苗者的第 14 天受 Spike 刺激的 T 细胞培养物中测序 T 细胞受体库,与 CD8 相比,CD4 T 细胞库更为多样化。尽管如此,CD8 克隆型占 Spike 特异性库的一半以上。我们的纵向分析显示,T 细胞反应在第 14 天达到峰值,然后下降到第 6 个月。值得注意的是,在接种疫苗后至少 6 个月,多个 T 细胞克隆型持续存在,如体外刺激所示。对 CDR3 区域的检查显示 CD4 和 CD8 克隆型中存在同源序列,主要 CD8 克隆型与 NYNYLYRLF 肽的注释序列具有高度相似性,表明潜在的免疫优势。总之,我们的研究证明了 Ad5-nCoV 腺病毒疫苗的免疫原性,并强调了其诱导强大和持久 T 细胞反应的能力。这些发现为疫苗对 COVID-19 的疗效提供了有价值的见解,并为控制传染病的持续努力提供了关键信息。