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


Lancet Microbe

Contributing to research themes:

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 270373 [IQR 203461–535188] antibody units [AU] per mL) were higher than in 111 infection-naive health-care workers following one dose (35001 [17099–55341] AU/mL; p<0·0001) and higher than in 25 infection-naive individuals given two doses (180904 [108221–242467] 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.

Author list:

*Contributed equally

† Contributed equally 

^Corresponding authors 

+Additional consortium members in the Appendix


Author Affiliations

1) Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK

2) Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, UK

3) HPRU in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK

4) Translational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, UK

5) Sir William Dunn School of Pathology, Division of Medical Sciences, University of Oxford, UK 

6) Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford, UK

7) Centre For Tropical Medicine and Global Health, Nuffield Dept. of Clinical Medicine, University of Oxford, UK

8) Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand

9) Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

10) Oxford University Hospitals NHS Foundation Trust, Oxford UK

11) Nuffield Dept of Clinical Neuroscience, University of Oxford, UK

12) Public Health England, Colindale, London, UK

13) Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, UK

14) Peter Medawar Building for Pathogen Research, Dept of Paediatrics, University of Oxford, UK

15) Oxford Vaccine Group, Department of Paediatrics, University of Oxford, UK

16) NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK 

17) Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, UK

18) University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

19) Faculty of Medicine, Department of Infectious Disease, Imperial College London, UK

20) NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, University of Oxford, UK

21) Translational Gastroenterology Unit, University of Oxford, UK

22) Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust, member of Liverpool Health Partners, UK


Adrienn Angyal1*, Stephanie Longet2*, Shona Moore3*, Rebecca P. Payne4*, Adam Harding5*, Tom Tipton2, Patpong Rongkard6,7,8, Mohammad Ali6,7, Luisa M Hering3 , Naomi Meardon9 , James Austin3 , Rebecca Brown1 , Donal Skelly6,10,11, Natalie Gillson12, Sue L Dobson3 , Andrew Cross13, Gurjinder Sandhar1 , Jonathan A. Kilby1 , Jessica K Tyerman4 , Alexander R Nicols4 , Jarmila  S Spegarova4 , Hema Mehta6 , Hailey Hornsby1 , Rachel Whitham9 , Christopher P. Conlon10, Katie Jeffery10, Philip Goulder14, John Frater6,10, Christina Dold15,16, Matthew Pace6 , Ane Ogbe6 , Helen Brown6 , M. Azim Ansari6 , Emily Adland14, Anthony Brown6 , Meera Chand12, Adrian Shields17,18, Philippa C. Matthews6,10 , Susan Hopkins12,19,20, Victoria Hall12,20, William James5 , Sarah L. Rowland-Jones1 , Paul Klenerman6,10,16,21^, Susanna Dunachie6,7,8,10^, Alex Richter17,18†, Chris Duncan4,13†, Eleanor Barnes6,10,16,21†, Miles Carroll5†, Lance Turtle3,22†, Thushan I. de Silva1,9† on behalf of the PITCH Consortium+