Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial
Feng-Cai Zhu*, Yu-Hua Li*, Xu-Hua Guan, Li-Hua Hou, Wen-Juan Wang, Jing-Xin Li, Shi-Po Wu, Bu-Sen Wang, Zhao Wang, Lei Wang, Si-Yue Jia, Hu-Dachuan Jiang, Ling Wang, Tao Jiang, Yi Hu, Jin-Bo Gou, Sha-Bei Xu, Jun-Jie Xu, Xue-Wen Wang, Wei Wang, Wei Chen
Summary
Background A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain.
Methods We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5×10¹⁰, 1×10¹¹, and 1·5×10¹¹ viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127.
Findings Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination.
Interpretation The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.
----from www.thelancet.com
百度翻译：
重组腺病毒5型载体COVID-19疫苗的安全性、耐受性和免疫原性：剂量递增、开放标签、非随机、首次人体试验
Feng-Cai Zhu*, Yu-Hua Li*, Xu-Hua Guan, Li-Hua Hou, Wen-Juan Wang, Jing-Xin Li, Shi-Po Wu, Bu-Sen Wang, Zhao Wang, Lei Wang, Si-Yue Jia, Hu-Dachuan Jiang, Ling Wang, Tao Jiang, Yi Hu, Jin-Bo Gou, Sha-Bei Xu, Jun-Jie Xu, Xue-Wen Wang, Wei Wang, Wei Chen
摘要
背景迫切需要一种针对COVID-19的疫苗。我们旨在评估表达严重急性呼吸综合征冠状病毒2株（SARS-CoV-2）棘突糖蛋白的重组腺病毒5型（Ad5）载体COVID-19疫苗的安全性、耐受性和免疫原性。
方法 在武汉市对Ad5载体COVID-19疫苗进行剂量递增、单中心、开放标签、非随机、1期试验。年龄在18至60岁之间的健康成人按顺序登记并分配到三个剂量组（5×10⁰、1×10{和1·5×10{）中的一个接受肌肉注射疫苗。主要结果是疫苗接种后7天的不良事件。在接种疫苗后28天内进行安全性评估。用ELISA检测特异性抗体，用SARS-CoV-2病毒中和试验和假病毒中和试验检测疫苗诱导的中和抗体反应。用酶联免疫斑点法和流式细胞仪检测T细胞反应。本研究注册于ClinicalTrials.gov网站，NCT 04313127。
发现 在2020年3月16日至27日期间，我们对195名个人进行了资格审查。其中108名受试者（男性51%，女性49%，平均年龄36.3岁）接受了低剂量（n=36）、中剂量（n=36）或高剂量（n=36）的疫苗接种。所有入选的参与者都被纳入分析。低剂量组30名（83%）受试者、中剂量组30名（83%）受试者和高剂量组27名（75%）受试者在接种疫苗后的前7天内至少出现一次不良反应。最常见的注射部位不良反应是疼痛，在58例（54%）疫苗接种者中有报道，最常见的系统性不良反应是发热（50例[46%]）、疲劳（47例[44%]）、头痛（42例[39%]）和肌肉疼痛（18例[17%]。所有剂量组报告的大多数不良反应在严重程度上都是轻或中度的。接种疫苗后28天内未发现严重不良事件。ELISA抗体和中和抗体在第14天显著增加，在接种后28天达到高峰。特异性T细胞反应在接种后第14天达到高峰。
解释 在接种后28天，Ad5载体COVID-19疫苗是可耐受和免疫原性的。健康成人对SARS-CoV-2的体液反应在接种后28天达到高峰，从接种后14天开始出现快速特异性T细胞反应。我们的发现表明，Ad5载体COVID-19疫苗值得进一步研究。
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