T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial

Type Journal Article Author Katie J. Ewer Author Jordan R. Barrett Author Sandra Belij-Rammerstorfer Author Hannah Sharpe Author Rebecca Makinson Author Richard Morter Author Amy Flaxman Author Daniel Wright Author Duncan Bellamy Author Mustapha Bittaye Author Christina Dold Author Nicholas M. Provine Author Jeremy Aboagye Author Jamie Fowler Author Sarah E. Silk Author Jennifer Alderson Author Parvinder K. Aley Author Brian Angus Author Eleanor Berrie Author Sagida Bibi Author Paola Cicconi Author Elizabeth A. Clutterbuck Author Irina Chelysheva Author Pedro M. Folegatti Author Michelle Fuskova Author Catherine M. Green Author Daniel Jenkin Author Simon Kerridge Author Alison Lawrie Author Angela M. Minassian Author Maria Moore Author Yama Mujadidi Author Emma Plested Author Ian Poulton Author Maheshi N. Ramasamy Author Hannah Robinson Author Rinn Song Author Matthew D. Snape Author Richard Tarrant Author Merryn Voysey Author Marion E. E. Watson Author Alexander D. Douglas Author Adrian V. S. Hill Author Sarah C. Gilbert Author Andrew J. Pollard Author Teresa Lambe URL https://www.nature.com/articles/s41591-020-01194-5 Rights 2020 The Author(s), under exclusive licence to Springer Nature America, Inc. Pages 1-9 Publication Nature Medicine ISSN 1546-170X Date 17/12/2020 Extra Publisher: Nature Publishing Group DOI 10.1038/s41591-020-01194-5 Library Catalog www.nature.com Language en Abstract Severe 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.