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AZD1222/ChAdOx1 nCoV-19 vaccination induces a polyfunctional spike protein–specific TH1 response with a diverse TCR repertoire
Science Translational Medicine ( IF 17.1 ) Pub Date : 2021-09-30 , DOI: 10.1126/scitranslmed.abj7211
Phillip A Swanson 1 , Marcelino Padilla 1 , Wesley Hoyland 1 , Kelly McGlinchey 2 , Paul A Fields 3 , Sagida Bibi 4 , Saul N Faust 5 , Adrian B McDermott 1 , Teresa Lambe 6, 7 , Andrew J Pollard 4 , Nicholas M Durham 8 , Elizabeth J Kelly 9 ,
Affiliation  

AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus–vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 in clinical trials and real-world studies. We characterized CD4+ and CD8+ T cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells from 296 unique vaccine recipients aged 18 to 85 years who enrolled in the phase 2/3 COV002 trial. Total spike protein–specific CD4+ T cell helper type 1 (TH1) and CD8+ T cell responses were increased in AZD1222-vaccinated adults of all ages after two doses of AZD1222. CD4+ TH2 responses after AZD1222 vaccination were not detected. Furthermore, AZD1222-specific TH1 and CD8+ T cells both displayed a high degree of polyfunctionality in all adult age groups. T cell receptor β (TCRβ) sequences from vaccinated participants mapped against TCR sequences known to react to SARS-CoV-2 revealed substantial breadth and depth across the SARS-CoV-2 spike protein for both AZD1222-induced CD4+ and CD8+ T cell responses. Overall, AZD1222 vaccination induced a polyfunctional TH1-dominated T cell response, with broad CD4+ and CD8+ T cell coverage across the SARS-CoV-2 spike protein.

中文翻译:

AZD1222/ChAdOx1 nCoV-19 疫苗接种可诱导具有多种 TCR 库的多功能刺突蛋白特异性 TH1 反应

AZD1222 (ChAdOx1 nCoV-19) 是一种复制缺陷型猿猴腺病毒载体疫苗,已在临床试验和现实世界研究中证明其对 2019 冠状病毒病的安全性、有效性和免疫原性。我们对参加 2/3 期 COV002 试验的 296 名年龄在 18 至 85 岁的独特疫苗接种者的外周血单核细胞中 AZD1222 疫苗接种诱导的 CD4 + 和 CD8 + T 细胞反应进行表征在接种两剂 AZD1222 后,所有年龄段接种 AZD1222 的成年人的总刺突蛋白特异性 CD4 + T 细胞辅助 1 型 (T H 1) 和 CD8 + T 细胞反应增加。CD4 + T H未检测到 AZD1222 疫苗接种后的 2 次反应。此外,AZD1222 特异性 T H 1 和 CD8 + T 细胞在所有成人年龄组中都显示出高度的多功能性。接种疫苗的参与者的 T 细胞受体 β (TCRβ) 序列映射到已知对 SARS-CoV-2 有反应的 TCR 序列,揭示了 AZD1222 诱导的 CD4 +和 CD8 + T 细胞的 SARS-CoV-2 刺突蛋白的广度和深度回应。总体而言,AZD1222 疫苗接种诱导了多功能 T H 1 主导的 T 细胞反应,在 SARS-CoV-2 刺突蛋白上具有广泛的 CD4 +和 CD8 + T 细胞覆盖。
更新日期:2021-11-18
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