NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.
China National Institute for Food and Drug Control, Beijing, China.
Lancet. 2020 Jun 13;395(10240):1845-1854. doi: 10.1016/S0140-6736(20)31208-3. Epub 2020 May 22.
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.
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 × 10, 1 × 10, and 1·5 × 10 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.
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.
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.
National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.
急需一种预防 COVID-19 的疫苗。本研究旨在评估表达严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）刺突糖蛋白的重组 5 型腺病毒（Ad5）载体 COVID-19 疫苗的安全性、耐受性和免疫原性。
我们在中国武汉进行了一项 Ad5 载体 COVID-19 疫苗的剂量递增、单中心、开放性、非随机、1 期临床试验。18 至 60 岁的健康成年人按顺序入组，并分为三组（5×10、1×10 和 1.5×10 病毒颗粒）接受肌肉内注射疫苗。主要终点是接种后 7 天内的不良事件。接种后 28 天内评估安全性。使用 ELISA 测量特异性抗体，使用 SARS-CoV-2 病毒中和和假病毒中和试验检测接种诱导的中和抗体反应。通过酶联免疫斑点和流式细胞术检测 T 细胞反应。本研究在 ClinicalTrials.gov 注册，注册号为 NCT04313127。
2020 年 3 月 16 日至 3 月 27 日，我们筛选了 195 名符合条件的患者。其中，108 名参与者（51%为男性，49%为女性；平均年龄 36.3 岁）入组并接受了低剂量（n=36）、中剂量（n=36）或高剂量（n=36）疫苗接种。所有入组的参与者均纳入分析。接种后 7 天内至少有 1 名参与者出现不良事件，低剂量组为 30 名（83%），中剂量组为 30 名（83%），高剂量组为 27 名（75%）。最常见的注射部位不良事件是疼痛，有 58 名（54%）疫苗接种者报告了该反应，最常见的全身不良事件是发热（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事件均为轻度或中度。接种后 28 天内未发生严重不良事件。ELISA 抗体和中和抗体在接种后第 14 天显著增加，并在接种后第 28 天达到峰值。特异性 T 细胞反应在接种后第 14 天达到峰值。
Ad5 载体 COVID-19 疫苗在接种后 28 天内具有良好的耐受性和免疫原性。健康成年人接种后第 28 天针对 SARS-CoV-2 的体液免疫反应达到峰值，第 14 天出现快速的特异性 T 细胞反应。我们的研究结果表明，Ad5 载体 COVID-19 疫苗值得进一步研究。
国家重点研发计划、国家重大科技专项和康希诺生物。
