T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study

PITCH Consortium, Adrienn Angyal, Stephanie Longet, Shona C. Moore, Rebecca P. Payne, Adam Harding, Tom Tipton, Patpong Rongkard, Mohammad Ali, Luisa M. Hering, Naomi Meardon, James Austin, Rebecca Brown, Donal Skelly, Natalie Gillson, Sue L. Dobson, Andrew Cross, Gurjinder Sandhar, Jonathan A. Kilby, Jessica K. TyermanAlexander R. Nicols, Jarmila S. Spegarova, Hema Mehta, Hailey Hornsby, Rachel Whitham, Christopher P. Conlon, Katie Jeffery, Philip Goulder, John Frater, Christina Dold, Matthew Pace, Ane Ogbe, Helen Brown, M. Azim Ansari, Emily Adland, Anthony Brown, Meera Chand, Adrian Shields, Philippa C. Matthews, Susan Hopkins, Victoria Hall, William James, Sarah L. Rowland-Jones, Paul Klenerman, Susanna Dunachie*, Alex Richter, Christopher J.A. Duncan, Eleanor Barnes, Miles Carroll, Lance Turtle, Thushan de Silva

*Corresponding author for this work

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Abstract

Background: Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer–BioNTech) mRNA vaccine. 

Methods: We sampled health-care workers enrolled in the PITCH study across four hospital sites in the UK (Oxford, Liverpool, Newcastle, and Sheffield). All health-care workers aged 18 years or older consenting to participate in this prospective cohort study were included, with no exclusion criteria applied. Blood samples were collected where possible before vaccination and 28 (±7) days following one or two doses (given 3–4 weeks apart) of the BNT162b2 vaccine. Previous infection was determined by a documented SARS-CoV-2-positive RT-PCR result or the presence of positive anti-SARS-CoV-2 nucleocapsid antibodies. We measured spike-specific IgG antibodies and quantified T-cell responses by interferon-γ enzyme-linked immunospot assay in all participants where samples were available at the time of analysis, comparing SARS-CoV-2-naive individuals to those with previous infection. 

Findings: Between Dec 9, 2020, and Feb 9, 2021, 119 SARS-CoV-2-naive and 145 previously infected health-care workers received one dose, and 25 SARS-CoV-2-naive health-care workers received two doses, of the BNT162b2 vaccine. In previously infected health-care workers, the median time from previous infection to vaccination was 268 days (IQR 232–285). At 28 days (IQR 27–33) after a single dose, the spike-specific T-cell response measured in fresh peripheral blood mononuclear cells (PBMCs) was higher in previously infected (n=76) than in infection-naive (n=45) health-care workers (median 284 [IQR 150–461] vs 55 [IQR 24–132] spot-forming units [SFUs] per 106 PBMCs; p<0·0001). With cryopreserved PBMCs, the T-cell response in previously infected individuals (n=52) after one vaccine dose was equivalent to that of infection-naive individuals (n=19) after receiving two vaccine doses (median 152 [IQR 119–275] vs 162 [104–258] SFUs/106 PBMCs; p=1·00). Anti-spike IgG antibody responses following a single dose in 142 previously infected health-care workers (median 270 373 [IQR 203 461–535 188] antibody units [AU] per mL) were higher than in 111 infection-naive health-care workers following one dose (35 001 [17 099–55 341] AU/mL; p<0·0001) and higher than in 25 infection-naive individuals given two doses (180 904 [108 221–242 467] AU/mL; p<0·0001). 

Interpretation: A single dose of the BNT162b2 vaccine is likely to provide greater protection against SARS-CoV-2 infection in individuals with previous SARS-CoV-2 infection, than in SARS-CoV-2-naive individuals, including against variants of concern. Future studies should determine the additional benefit of a second dose on the magnitude and durability of immune responses in individuals vaccinated following infection, alongside evaluation of the impact of extending the interval between vaccine doses. 

Funding: UK Department of Health and Social Care, and UK Coronavirus Immunology Consortium.

Original languageEnglish
Pages (from-to)e21-e31
JournalThe Lancet Microbe
Volume3
Issue number1
Early online date9 Nov 2021
DOIs
Publication statusPublished - 1 Jan 2022

Bibliographical note

Funding Information: We express our gratitude to all participants who took part in this study. In Sheffield, participants were recruited under the Sheffield Teaching Hospitals Observational Study of Patients with Pulmonary Hypertension, Cardiovascular and other Respiratory Diseases (STH-Obs; 18/YH/0441), which was amended for this study on Sept 10, 2020. In Oxford, participants were recruited under the GI Biobank Study 16/YH/0247, approved by the research ethics committee at Yorkshire and The Humber—Sheffield Research Ethics Committee on July 29, 2016, which was amended for this purpose on June 8, 2020. In Liverpool, some participants were recruited under the “Human immune responses to acute virus infections” Study (16/NW/0170), approved by North West—Liverpool Central Research Ethics Committee on March 8, 2016, and last amended on Sept 14, 2020. This work was funded by the UK Department of Health and Social Care as part of the PITCH Consortium, with a contribution from the UK Coronavirus Immunology Consortium and the Huo Family Foundation. TIdS is funded by a Wellcome Trust Intermediate Clinical Fellowship award (110058/Z/15/Z). MC, LT, SL, and TT are funded by US Food and Drug Administration Medical Countermeasures Initiative grants HHSF223201510104C and 75F40120C00085: Characterization of severe coronavirus infection in humans and model systems for MCM development and evaluation. The Article reflects the views of the authors and does not represent the views or policies of the US Food and Drug Administration (FDA). MAA is supported by the Wellcome Trust and Royal Society (220171/Z/20/Z). EB and PK are NIHR Senior Investigators and PK is funded by the US National Institutes of Health (grants WT109965MA and U19 I082360). SD is funded by an NIHR Global Research Professorship (NIHR300791). PCM is funded by a Wellcome intermediate fellowship (110110/Z/15/Z). DS is supported by the NIHR Academic Clinical Fellow programme in Oxford. LT is supported by the Wellcome Trust (grant number 205228/Z/16/Z) and by the University of Liverpool Centre for Excellence in Infectious Disease Research. LT and PK are in the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections (NIHR200907) at the University of Liverpool in partnership with Public Health England, in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. PK is funded by a COVID-19 Rapid Response Grant (COV19-RECLPA) from the Department of Health and Social Care, UKRI, and NIHR. RPP is funded by the Wellcome Trust Career Re-entry fellowship (204721/Z/16/Z). CJAD is a Wellcome Trust Clinical Research Career Development Fellow (211153/Z/18/Z) and is part-funded by the Barbour Foundation and the UK Coronavirus Immunology Consortium. The views expressed are those of the authors and not necessarily those of the UK Department of Health and Social Care, the NHS, the NIHR, or Public Health England. The STH-ObS was supported by the British Heart Foundation (PG/11/116/29288). The STH-ObS Chief Investigator, Allan Lawrie, is supported by a British Heart Foundation Senior Basic Science Research fellowship (FS/18/52/33808). We gratefully acknowledge financial support from the UK Department of Health via the Sheffield NIHR Clinical Research Facility award to the Sheffield Teaching Hospitals Foundation NHS Trust.

CD worked on the Oxford–AstraZeneca COVID-19 vaccine trial (phase 1–3). AO reports personal fees from Take Two Interactive and personal fees from Genome BC, outside the submitted work. PCM reports grants from the Wellcome Trust during the conduct of the study. SLR-J reports grants from the UK Department of Health and Social Care during the conduct of the study and grants from UK Research and Innovation (UKRI), National Institute for Health Research (NIHR), and Global Challenges Research Fund outside the submitted work. SD reports grants from the UK Department of Health and Social Care, UK Coronavirus Immunology Consortium (UKRI), the Huo Family Foundation, and the NIHR during the conduct of the study. CJAD reports grants from the Wellcome Trust during the conduct of the study. LT reports personal fees from Eisai outside the submitted work. All other authors declare no competing interests.

Open Access: This is an Open Access article under the CC BY 4.0 license.

Publisher Copyright: © 2021 The Author(s). Published by Elsevier Ltd.

Citation: Angyal, A et al, T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study, The Lancet Microbe, Volume 3, Issue 1, 2022, Pages e21-e31, ISSN 2666-5247, https://doi.org/10.1016/S2666-5247(21)00275-5.

DOI: https://doi.org/10.1016/S2666-5247(21)00275-5.

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