Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial
Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial
复制标题
DOI：
10.1016/s0140-6736(20)31604-4
复制
发表时间：
2020-08-15
期刊：
影响因子：
168.9
通讯作者：
Pollard, Andrew J.
中科院分区：
文献类型：
--
作者：
Folegatti, Pedro M.;Ewer, Katie J.;Pollard, Andrew J.
背景严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的流行可以通过接种疫苗来遏制。我们评价了表达SARS-CoV-2刺突蛋白的病毒载体冠状病毒疫苗(ChAdOx1 nCoV-19)的安全性、反应性和免疫原性。方法以脑膜炎球菌结合疫苗(MenACWY)为对照，在英国的5个试验点进行了1/2期单盲随机对照试验。健康成人年龄18~55岁，无实验室确诊的SARS-CoV-2感染史或新冠肺炎样症状。随机分为两组，分别接受ChAdOx1nCoV-19 5×10(10)病毒颗粒或MenACWY单次肌肉注射。五个地点中的两个地点的方案修正案允许在接种疫苗前给予预防性扑热息痛。被分配到非随机、非盲目ChAdOx1 nCoV-19 Prime-Boost组的10名参与者接受了两剂疫苗的时间表，在第一剂疫苗接种28天后接种。使用针对SARS-CoV-2刺突蛋白的标准化总免疫吸附试验、多重免疫分析、三种活的SARS-CoV-2中和试验(50%空斑减少中和试验[PRNT50]；微中和试验[MNA(50)、MNA(80)和MNA(90)]；以及Marburg VN)来评估基线和接种后的体液反应。用体外干扰素-伽马酶联免疫斑点试验评估细胞反应。共同的主要结果是评估疗效(以症状病毒学确诊的新冠肺炎病例来衡量)和安全性(以严重不良事件的发生来衡量)。分析是通过对接种疫苗的参与者进行分组分配完成的。在接种疫苗后28天内对安全性进行评估。在这里，我们报告了关于安全性、反应性以及细胞和体液免疫反应的初步研究结果。这项研究正在进行中，并在ISRCTN，15281137和ClinicalTrials.gov，NCT04324606上注册。研究结果在2020年4月23日至5月21日期间，1,077名参与者被登记并分配接受ChAdOx1nCoV-19(n=543)或MenACWY(n=534)，其中10人登记在非随机CHAdOx1nCoV-19 Prime-Boost组。局部和全身反应在ChAdOx1nCoV-19组中更为常见，许多通过预防性使用扑热息痛得到缓解，包括疼痛、感觉发热、寒战、肌肉疼痛、头痛和不适(均P
Background The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2.Methods We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18-55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 x 10(10) viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 eutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA(50), MNA(80), and MNA(90)]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-gamma enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606.Findings Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p