本文摘譯自The Lance《柳葉刀》雜志?2020年5月22日

以下為詳文

摘要

研究背景

迫切需要一種預(yù)防COVID-19的疫苗。我們旨在評估重組腺病毒5型（Ad5）載體COVID-19疫苗的安全性，耐受性和免疫原性，表達(dá)一種嚴(yán)重急性呼吸綜合征冠狀病毒2株（SARS-CoV-2）的棘突糖蛋白。

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研究方法

我們在中國武漢進(jìn)行了Ad5載體COVID-19疫苗的劑量遞增、單中心、開放標(biāo)簽、非隨機(jī)、Ⅰ期臨床試驗(yàn)。年齡在18至60歲之間的健康成人按順序登記，并分配到三個(gè)劑量組之一（5×1010、1×1011和1.5×1011病毒顆粒），接受肌肉注射疫苗。主要結(jié)果是：接種疫苗后7天的不良事件；接種疫苗后28天內(nèi)進(jìn)行安全性評估；采用ELISA檢測特異性抗體；采用SARS-CoV-2病毒中和測試和假病毒中和測試檢測疫苗誘導(dǎo)的中和抗體反應(yīng)；采用酶聯(lián)免疫斑點(diǎn)試驗(yàn)和流式細(xì)胞試驗(yàn)檢測T細(xì)胞反應(yīng)。本研究已在ClinicalTrials.gov上注冊，NCT 04313127。

研究結(jié)果

在2020年3月16日至3月27日期間，我們篩選了195名符合條件的人。其中，108名受試者（男性51%，女性49%，平均年齡36.3歲）接受了低劑量（n=36）、中劑量（n=36）或高劑量（n=36）的疫苗接種。所有登記的參與者都被納入分析。低劑量組30名（83%）受試者、中劑量組30名（83%）受試者和高劑量組27名（75%）受試者在接種疫苗后的前7天內(nèi)至少出現(xiàn)一次不良反應(yīng)。注射部位最常見的不良反應(yīng)是疼痛，58名（54%）疫苗接受者報(bào)告了這種情況；最常見的系統(tǒng)性不良反應(yīng)是發(fā)熱（50[46%]）、疲勞（47[44%]）、頭痛（42[39%]）和肌肉疼痛（18[17%]。所有劑量組報(bào)告的大多數(shù)不良反應(yīng)在嚴(yán)重程度上都是輕度或中度的，接種疫苗后28天內(nèi)未發(fā)現(xiàn)嚴(yán)重不良事件。ELISA抗體和中和抗體在第14天顯著增加，接種后28天達(dá)到高峰，特異性T細(xì)胞反應(yīng)在接種后第14天達(dá)到高峰。

研究說明

在疫苗接種后28天，Ad5載體COVID-19疫苗是可耐受和免疫原性的。健康成人對SARS-CoV-2的體液反應(yīng)在接種后28天達(dá)到高峰，接種后第14天觀察到快速特異性T細(xì)胞反應(yīng)。我們的研究結(jié)果表明，Ad5載體COVID-19疫苗值得進(jìn)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）