英国牛津COVID疫苗试验小组报道了SARS-CoV-2疫苗ChAdOx1 nCoV-19剂量加强的1/2期试验结果。2020年12月17日，国际知名学术期刊《自然—医学》在线发表了这一成果。

研究人员表示，目前正在开发190多种疫苗来预防SARS-CoV-2的感染。动物研究表明，虽然中和针对病毒性突刺蛋白的抗体可能与保护相关，但其他抗体功能在预防感染中也可能很重要。之前，研究人员在18-55岁健康成年人的单盲1/2期随机对照试验中报道了病毒载体冠状病毒疫苗ChAdOx1 nCoV-19（AZD1222）的早期免疫原性和安全性结果（NCT04324606）。

研究人员从该试验的志愿者亚组中报道了疫苗的安全性和探索性体液及细胞免疫原性，在初次接种后56天，这些志愿者随后被分配接受同源的全剂量（SD/SD D56; n=20）或半剂量（SD/LD D56；n=32）ChAdOx1加强疫苗。研究人员还提供了以前报道的28天间隔初免-加强免疫组（SD/SD D28；n=10）的免疫原性数据来方便比较。此外，研究人员描述了使用对照疫苗加强免疫的志愿者（MenACWY；n=10）。

研究人员证明了ChAdOx1 nCoV-19的加强剂量比初始剂量更安全，耐受性更好。使用系统血清学方法，演技润园还证明了抗突刺中和抗体滴度以及Fc介导的功能性抗体反应（包括抗体依赖性嗜中性粒细胞/单核细胞吞噬作用、补体激活和自然杀伤细胞激活）可通过加强剂量大大增强疫苗。加强剂量疫苗诱导的抗体应答比节省剂量的半剂量加强疫苗应答强，尽管T细胞应答的幅度不会随两种加强剂量的增加而增加。这些数据支持目前正在3期临床试验中评估的两剂量疫苗方案。

附：英文原文

Title: Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses

Author: Jordan R. Barrett, Sandra Belij-Rammerstorfer, Christina Dold, Katie J. Ewer, Pedro M. Folegatti, Ciaran Gilbride, Rachel Halkerston, Jennifer Hill, Daniel Jenkin, Lisa Stockdale, Marije K. Verheul, Parvinder K. Aley, Brian Angus, Duncan Bellamy, Eleanor Berrie, Sagida Bibi, Mustapha Bittaye, Miles W. Carroll, Breeze Cavell, Elizabeth A. Clutterbuck, Nick Edwards, Amy Flaxman, Michelle Fuskova, Andrew Gorringe, Bassam Hallis, Simon Kerridge, Alison M. Lawrie, Aline Linder, Xinxue Liu, Meera Madhavan, Rebecca Makinson, Jack Mellors, Angela Minassian, Maria Moore, Yama Mujadidi, Emma Plested, Ian Poulton, Maheshi N. Ramasamy, Hannah Robinson, Christine S. Rollier, Rinn Song, Matthew D. Snape, Richard Tarrant, Stephen Taylor, Kelly M. Thomas, Merryn Voysey, Marion E. E. Watson, Daniel Wright, Alexander D. Douglas, Catherine M. Green, Adrian V. S. Hill, Teresa Lambe, Sarah Gilbert, Andrew J. Pollard

Issue&Volume: 2020-12-17

Abstract: More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18–55 years (NCT04324606). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n=20) or half-dose (SD/LD D56; n=32) ChAdOx1 booster vaccine 56d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n=10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n=10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.

DOI: 10.1038/s41591-020-01179-4

Source: https://www.nature.com/articles/s41591-020-01179-4