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T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial
Nature Medicine ( IF 58.7 ) Pub Date : 2020-12-17 , DOI: 10.1038/s41591-020-01194-5
Katie J Ewer 1 , Jordan R Barrett 1 , Sandra Belij-Rammerstorfer 1 , Hannah Sharpe 1 , Rebecca Makinson 1 , Richard Morter 1 , Amy Flaxman 1 , Daniel Wright 1 , Duncan Bellamy 1 , Mustapha Bittaye 1 , Christina Dold 2 , Nicholas M Provine 3 , Jeremy Aboagye 1 , Jamie Fowler 1 , Sarah E Silk 1 , Jennifer Alderson 4 , Parvinder K Aley 2 , Brian Angus 3 , Eleanor Berrie 5 , Sagida Bibi 2 , Paola Cicconi 2 , Elizabeth A Clutterbuck 2 , Irina Chelysheva 2 , Pedro M Folegatti 1 , Michelle Fuskova 1 , Catherine M Green 5 , Daniel Jenkin 1 , Simon Kerridge 2 , Alison Lawrie 1 , Angela M Minassian 1 , Maria Moore 2 , Yama Mujadidi 2 , Emma Plested 2 , Ian Poulton 1 , Maheshi N Ramasamy 2 , Hannah Robinson 2 , Rinn Song 2 , Matthew D Snape 2 , Richard Tarrant 5 , Merryn Voysey 2 , Marion E E Watson 1 , Alexander D Douglas 1 , Adrian V S Hill 1 , Sarah C Gilbert 1 , Andrew J Pollard 2 , Teresa Lambe 1 ,
Affiliation  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses2 and might reduce the potential for disease enhancement3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection4. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. 5,6). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)7 given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18–55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4+ T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8+ T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy.



中文翻译:


在 1/2 期临床试验中,单剂 ChAdOx1 nCoV-19 (AZD1222) 疫苗诱导 T 细胞和抗体反应



严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 是 2019 年冠状病毒病 (COVID-19) 的病原体,已引起全球大流行,迫切需要安全、有效的疫苗1 。强烈的、Th1 倾向的 T 细胞反应可以驱动保护性体液和细胞介导的免疫反应2 ,并可能降低疾病增强的可能性3 。细胞毒性 T 细胞清除病毒感染的宿主细胞并有助于控制感染4 。对感染 SARS-CoV-2 的患者的研究表明,体液和细胞介导的免疫反应在 COVID-19 康复过程中具有保护作用(参考文献5,6 )。 ChAdOx1 nCoV-19 (AZD1222) 是一种候选 SARS-CoV-2 疫苗,包含表达全长 SARS-CoV-2 刺突蛋白的复制缺陷型猿腺病毒。我们最近报告了 ChAdOx1 nCoV-19 疫苗 (NCT04400838) 7的 1/2 期试验的初步安全性和免疫原性数据,该疫苗以一剂或两剂方案给药。该疫苗具有耐受性,可诱导针对 SARS-CoV-2 刺突蛋白的中和抗体和抗原特异性 T 细胞。在这里,我们详细描述了本试验中 18-55 岁成人在接种单剂 ChAdOx1 nCoV-19 疫苗后长达 8 周的免疫反应的探索性分析,证明了 Th1 偏向反应的诱导其特征是 CD4 + T 细胞分泌干扰素-γ 和肿瘤坏死因子-α 细胞因子,以及主要产生 IgG1 和 IgG3 亚类的抗体。还诱导了单功能、多功能和细胞毒性表型的CD8 + T细胞。 总而言之,这些结果表明 ChAdOx1 nCoV-19 疫苗诱导了良好的免疫特征,支持该候选疫苗进入正在进行的 2/3 期试验以评估疫苗功效。

更新日期:2020-12-17
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