本文摘译自The Lance《柳叶刀》杂志 2020年5月22日

以下为详文

摘要

研究背景

迫切需要一种预防COVID-19的疫苗。我们旨在评估重组腺病毒5型（Ad5）载体COVID-19疫苗的安全性，耐受性和免疫原性，表达一种严重急性呼吸综合征冠状病毒2株（SARS-CoV-2）的棘突糖蛋白。

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研究方法

我们在中国武汉进行了Ad5载体COVID-19疫苗的剂量递增、单中心、开放标签、非随机、Ⅰ期临床试验。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之一（5×1010、1×1011和1.5×1011病毒颗粒），接受肌肉注射疫苗。主要结果是：接种疫苗后7天的不良事件；接种疫苗后28天内进行安全性评估；采用ELISA检测特异性抗体；采用SARS-CoV-2病毒中和测试和假病毒中和测试检测疫苗诱导的中和抗体反应；采用酶联免疫斑点试验和流式细胞试验检测T细胞反应。本研究已在ClinicalTrials.gov上注册，NCT 04313127。

研究结果

在2020年3月16日至3月27日期间，我们筛选了195名符合条件的人。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。所有登记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。注射部位最常见的不良反应是疼痛，58名（54%）疫苗接受者报告了这种情况；最常见的系统性不良反应是发热（50[46%]）、疲劳（47[44%]）、头痛（42[39%]）和肌肉疼痛（18[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度或中度的，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，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。

研究说明

在疫苗接种后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，接种后第14天观察到快速特异性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。

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（下文略）

原文：

Published in The Lancet Journal on May 22, 2020

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.

Funding

National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.

（The following is omitted）