• Katie J Ewer, Jordan R Barrett, Sandra Belij-Rammerstorfer, Hannah Sharpe, Rebecca Makinson, Richard Morter, Amy Flaxman, Daniel Wright, Duncan Bellamy, Mustapha Bittaye, Christina Dold, Nicholas M Provine, Jeremy Aboagye, Jamie Fowler, Sarah E Silk, Jennifer Alderson, Parvinder K Aley, Brian Angus, Eleanor Berrie, Sagida Bibi, Paola Cicconi, Elizabeth A Clutterbuck, Irina Chelysheva, Pedro M Folegatti, Michelle Fuskova, Catherine M Green, Daniel Jenkin, Simon Kerridge, Alison Lawrie, Angela M Minassian, Maria Moore, Yama Mujadidi, Emma Plested, Ian Poulton, Maheshi N Ramasamy, Hannah Robinson, Rinn Song, Matthew D Snape, Richard Tarrant, Merryn Voysey, Marion E E Watson, Alexander D Douglas, Hill Adrian V S AVS http://orcid.org/0000-0003-0900-9629 The Jenner Institute, University of Oxford, Oxford, UK., Sarah C Gilbert, Andrew J Pollard, Teresa Lambe, and Oxford COVID Vaccine Trial Group.
• The Jenner Institute, University of Oxford, Oxford, UK. katie.ewer@ndm.ox.ac.uk.
• Nat. Med. 2021 Feb 1; 27 (2): 270-278.

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses2 and might reduce the potential for disease enhancement3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection4. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. 5,6). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)7 given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18-55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4+ T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8+ T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy.

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