• 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, Hill Adrian V S AVS http://orcid.org/0000-0003-0900-9629 The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Teresa Lambe, Sarah Gilbert, Andrew J Pollard, and Oxford COVID Vaccine Trial Group.
• The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
• Nat. Med. 2021 Feb 1; 27 (2): 279-288.

AbstractMore 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 56 d 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.

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