英国牛津大学Andrew J Pollard团队发布了抗SARS-CoV-2的ChAdOx1 nCoV-19疫苗的临床试验报告。2020年7月20日出版的《柳叶刀》杂志发表了这项成果。

研究组评估了表达SARS-CoV-2刺突蛋白的病毒载体冠状病毒疫苗的安全性、反应原性和免疫原性。

研究组在英国的五个试验点进行了一项临床1/2期、单盲、随机对照试验，研究表达SARS-CoV-2刺突蛋白的黑猩猩腺病毒载体疫苗（ChAdOx1 nCoV-19）的效果，以脑膜炎球菌结合疫苗（MenACWY）作为对照。

2020年4月23日至5月21日，研究组招募了1077名年龄为18–55岁、无实验室确诊SARS-CoV-2感染史或COVID-19样症状的健康成年人，将其按1：1随机分组，其中543名以5×10¹⁰病毒颗粒的剂量接种ChAdOx1 nCoV-19，534名接受单次肌内注射MenACWY。分配给非随机、非盲ChAdOx1 nCoV-19初免-加强免疫组的10名参与者接受了两剂方案，第一剂接种28天后接种了加强疫苗。

在ChAdOx1 nCoV-19组中，局部和全身反应更为普遍，而预防性扑热息痛的使用可减轻许多局部反应和全身反应，包括疼痛、发烧、发冷、肌肉酸痛、头痛和不适。未发生与ChAdOx1 nCoV-19相关的严重不良事件。

在ChAdOx1 nCoV-19组中，刺突蛋白特异性T细胞反应在第14天达到峰值。到第28天时，抗刺突蛋白IgG应答上升（127例），并在第二剂后得到加强（10例）。单次接种后，以MNA80来评估，35名受试者中有32名（91%）检测到抗SARS-CoV-2的中和抗体反应；以PRNT50来评估，35名（100%）参与者均检测到中和抗体反应。接种加强疫苗后，所有受试者都出现中和活性。中和抗体反应与ELISA检测的抗体水平密切相关。

ChAdOx1 nCoV-19显示出可耐受的安全性，且同源加强抗体反应。研究结果及体液和细胞免疫反应诱导支持正在进行的临床3期试验，以便对该候选疫苗进行大规模评估。

附：英文原文

Title: 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

Author: Pedro M Folegatti, Katie J Ewer, Parvinder K Aley, Brian Angus, Stephan Becker, Sandra Belij-Rammerstorfer, Duncan Bellamy, Sagida Bibi, Mustapha Bittaye, Elizabeth A Clutterbuck, Christina Dold, Saul N Faust, Adam Finn, Amy L Flaxman, Bassam Hallis, Paul Heath, Daniel Jenkin, Rajeka Lazarus, Rebecca Makinson, Angela M Minassian, Katrina M Pollock, Maheshi Ramasamy, Hannah Robinson, Matthew Snape, Richard Tarrant, Merryn Voysey, Catherine Green, Alexander D Douglas, Adrian V S Hill, Teresa Lambe, Sarah C Gilbert, Andrew J Pollard, Jeremy Aboagye, Kelly Adams, Aabidah Ali, Elizabeth Allen, Jennifer L. Allison, Rachel Anslow, Edward H. Arbe-Barnes, Gavin Babbage, Kenneth Baillie, Megan Baker, Philip Baker, Ioana Baleanu, Juliana Ballaminut, Eleanor Barnes, Jordan Barrett, Louise Bates, Alexander Batten, Kirsten Beadon, Rebecca Beckley, Eleanor Berrie, Lisa Berry, Amy Beveridge, Kevin R. Bewley, Else Margreet Bijker, Tracey Bingham, Luke Blackwell, Caitlin L. Blundell, Emma Bolam, Elena Boland, Nicola Borthwick, Thomas Bower, Amy Boyd, Tanja Brenner, Philip D. Bright, Charlie Brown-OSullivan, Emily Brunt, Jamie Burbage, Sharon Burge, Karen R. Buttigieg, Nicholas Byard, Ingrid Cabera Puig, Anna Calvert, Susana Camara, Michelangelo Cao, Federica Cappuccini, Melanie Carr, Miles W. Carroll, Victoria Carter, Katrina Cathie, Ruth J. Challis, Irina Chelysheva, Jee-Sun Cho, Paola Cicconi, Liliana Cifuentes, Helen Clark, Elizabeth Clark, Tom Cole, Rachel Colin-Jones, Christopher P. Conlon, Aislinn Cook, Naomi S. Coombes, Rachel Cooper

Issue&Volume: 2020-07-20

Abstract: 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 5×1010 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 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ 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<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493–1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96–317; n=127), and were boosted following a second dose (639 EU, 360–792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001).

Interpretation

ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme.

Funding

UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gieen-Marburg-Langen.

DOI: 10.1016/S0140-6736(20)31604-4

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31604-4/fulltext