T-Cell and Antibody Responses to First BNT162b2 Vaccine Dose in Previously SARS-CoV-2-Infected and Infection-Naive UK Healthcare Workers: A Multicentre, Prospective, Observational Cohort Study

10.2139/ssrn.3812375

Preprints with The Lancet

Contributing to research themes:

This research has not been peer-reviewed. This is a preliminary report that should not be regarded as conclusive, guide clinical practice/health-related behaviour, or be reported in news media as established information.

Abstract

Background: Following a single dose of BNT162b2 mRNA vaccine, higher antibody titres are observed following prior SARS-CoV-2 infection than in infection-naive individuals, but T-cell responses are less well defined.

Methods: We sampled healthcare workers (HCWs) enrolled in the UK PITCH study, before and after BNT162b2 mRNA vaccination. We measured spike-specific antibody, and quantified T-cell responses by IFNγ ELISpot assay and intracellular staining of peripheral blood mononuclear cells (PBMC), comparing SARS-CoV-2-naïve individuals to those with prior infection.

Findings: HCWs aged 22 to 71 years received one (n=216) or two (n=21) vaccine doses. After a single dose, the spike-specific T-cell response was six-fold higher in previously-infected vs. naive individuals (median 340 vs. 58 SFU/106 PBMC, p<0.0001; fresh PBMC, n=99). The T-cell response in previously-infected individuals after one vaccine dose was equivalent to naïve individuals receiving two vaccine doses (median 158 vs. 165 SFU/106 PBMCs, p=0.65; cryopreserved PBMC, n=117). Anti-spike IgG levels following a single dose in those previously infected (median 512.9 antibody units/ml (AU/ml)) were 6.8-fold higher vs. naïve individuals following one dose (median 75.0 AU/ml, p<0.0001) and 2.9-fold higher than naïve individuals given two doses three weeks apart (179.9 AU/ml, p=0.03). Following vaccination, plasma from individuals with prior infection demonstrated higher in vitro neutralisation of the B.1.351 variant of concern compared to naive individuals.

Interpretation: Following a single BNT162b2 dose, HCWs with a prior history of SARS-CoV-2 infection have significantly higher T-cell and antibody responses than naive individuals.

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+