학술논문
T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial
Document Type
Article
Author
Ewer, Katie J.; Barrett, Jordan R.; Belij-Rammerstorfer, Sandra; Sharpe, Hannah; Makinson, Rebecca; Morter, Richard; Flaxman, Amy; Wright, Daniel; Bellamy, Duncan; Bittaye, Mustapha; Dold, Christina; Provine, Nicholas M.; Aboagye, Jeremy; Fowler, Jamie; Silk, Sarah E.; Alderson, Jennifer; Aley, Parvinder K.; Angus, Brian; Berrie, Eleanor; Bibi, Sagida; Cicconi, Paola; Clutterbuck, Elizabeth A.; Chelysheva, Irina; Folegatti, Pedro M.; Fuskova, Michelle; Green, Catherine M.; Jenkin, Daniel; Kerridge, Simon; Lawrie, Alison; Minassian, Angela M.; Moore, Maria; Mujadidi, Yama; Plested, Emma; Poulton, Ian; Ramasamy, Maheshi N.; Robinson, Hannah; Song, Rinn; Snape, Matthew D.; Tarrant, Richard; Voysey, Merryn; Watson, Marion E. E.; Douglas, Alexander D.; Hill, Adrian V. S.; Gilbert, Sarah C.; Pollard, Andrew J.; Lambe, Teresa
Source
Nature Medicine; February 2021, Vol. 27 Issue: 2 p270-278, 9p
Subject
Language
ISSN
10788956; 1546170X
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 responses2and 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)7given 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.