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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

55 Pages Posted: 25 Mar 2021

See all articles by Adrienn Angyal

Adrienn Angyal

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease

Stephanie Longet

University of Oxford - Wellcome Trust Centre for Human Genetics

Shona Moore

University of Liverpool - HPRU in Emerging and Zoonotic Infections

Rebecca P. Payne

Newcastle University - Translational and Clinical Research Institute

Adam Harding

University of Oxford - Sir William Dunn School of Pathology

Tom Tipton

University of Oxford - Wellcome Trust Centre for Human Genetics

Patpong Rongkard

University of Oxford - Peter Medawar Building for Pathogen Research

Mohammad Ali

University of Oxford - Peter Medawar Building for Pathogen Research

Luisa M. Hering

University of Liverpool - HPRU in Emerging and Zoonotic Infections

Naomi Meardon

Sheffield Teaching Hospitals NHS Foundation Trust

James Austin

University of Liverpool - HPRU in Emerging and Zoonotic Infections

Rebecca Brown

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease

Donal Skelly

University of Oxford - Nuffield Department of Clinical Neurosciences; Oxford University Hospitals NHS Foundation Trust

Natalie Gillson

Public Health England Colindale

Sue L. Dobson

University of Liverpool - HPRU in Emerging and Zoonotic Infections

Andrew Cross

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

Gurjinder Sandhar

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease

Jonathan A. Kilby

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease

Jessica K. Tyerman

Newcastle University - Translational and Clinical Research Institute

Alexander R. Nicols

Newcastle University - Translational and Clinical Research Institute

Jarmila S. Spegarova

Newcastle University - Translational and Clinical Research Institute

Hema Mehta

University of Oxford - Peter Medawar Building for Pathogen Research

Hailey Hornsby

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease

Rachel Whitham

Sheffield Teaching Hospitals NHS Foundation Trust

Christopher P. Conlon

Government of the United Kingdom - Oxford University Hospitals NHS Foundation Trust

Katie Jeffery

Government of the United Kingdom - Oxford University Hospitals NHS Foundation Trust

Philip Goulder

University of Oxford - Department of Paediatrics

John Frater

University of Oxford - Peter Medawar Building for Pathogen Research

Christina Dold

University of Oxford - Oxford Vaccine Group

Matthew Pace

University of Oxford - Peter Medawar Building for Pathogen Research

Ane Ogbe

University of Oxford - Peter Medawar Building for Pathogen Research

Helen Brown

University of Oxford - Peter Medawar Building for Pathogen Research

Azim M. Ansari

University of Oxford - Peter Medawar Building for Pathogen Research

Emily Adland

University of Oxford - Peter Medawar Building for Pathogen Research

Anthony Brown

University of Oxford - Peter Medawar Building for Pathogen Research

Meera A. Chand

Public Health England Colindale

Adrian Shields

University of Birmingham - Institute of Cancer and Genomic Sciences

Philippa Matthews

University of Oxford - Peter Medawar Building for Pathogen Research

Susan Hopkins

University of Oxford - NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance; Public Health England Colindale

Victoria Jane Hall

Public Health England Colindale; University of Oxford - NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance

William James

University of Oxford - Sir William Dunn School of Pathology

Sarah L. Rowland-Jones

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease

Paul Klenerman

University of Oxford - Peter Medawar Building for Pathogen Research

Susanna Dunachie

University of Oxford - Peter Medawar Building for Pathogen Research

Alex G. Richter

University of Birmingham - Clinical Immunology Service

Christopher J. A. Duncan

Newcastle upon Tyne Hospitals NHS Foundation Trust - Department of Infection and Tropical Medicine

Eleanor Barnes

Oxford University Hospitals NHS Foundation Trust

Miles W. Carroll

University of Oxford - Wellcome Centre for Human Genetics

Lance Turtle

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

Thushan I. de Silva

Sheffield Teaching Hospitals NHS Foundation Trust - South Yorkshire Regional Department of Infection and Tropical Medicine; University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease

PITCH Consortium

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Multiple version iconThere are 2 versions of this paper

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

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

Conflict of Interest: D.W.E. declares lecture fees from Gilead, outside the submitted work. The other authors have no conflicts of interest to declare.

Ethical Approval: PITCH was recognised as a sub-study of SIREN on 2 December 2020, which was approved by the Berkshire Research Ethics Committee, Health Research 250 Authority (IRAS ID 284460, REC reference 20/SC/0230).

Suggested Citation

Angyal, Adrienn and Longet, Stephanie and Moore, Shona and Payne, Rebecca P. and Harding, Adam and Tipton, Tom and Rongkard, Patpong and Ali, Mohammad and Hering, Luisa M. and Meardon, Naomi and Austin, James and Brown, Rebecca and Skelly, Donal and Gillson, Natalie and Dobson, Sue L. and Cross, Andrew and Sandhar, Gurjinder and Kilby, Jonathan A. and Tyerman, Jessica K. and Nicols, Alexander R. and Spegarova, Jarmila S. and Mehta, Hema and Hornsby, Hailey and Whitham, Rachel and Conlon, Christopher P. and Jeffery, Katie and Goulder, Philip and Frater, John and Dold, Christina and Pace, Matthew and Ogbe, Ane and Brown, Helen and Ansari, Azim M. and Adland, Emily and Brown, Anthony and Chand, Meera A. and Shields, Adrian and Matthews, Philippa and Hopkins, Susan and Hall, Victoria Jane and James, William and Rowland-Jones, Sarah L. and Klenerman, Paul and Dunachie, Susanna and Richter, Alex G. and Duncan, Christopher J. A. and Barnes, Eleanor and Carroll, Miles W. and Turtle, Lance and de Silva, Thushan I. and Consortium, PITCH, 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. Available at SSRN: https://ssrn.com/abstract=3812375 or http://dx.doi.org/10.2139/ssrn.3812375

Adrienn Angyal (Contact Author)

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease ( email )

Medical School
University of Sheffield
Sheffield, S10 2RX
United Kingdom

Stephanie Longet

University of Oxford - Wellcome Trust Centre for Human Genetics

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Shona Moore

University of Liverpool - HPRU in Emerging and Zoonotic Infections ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Rebecca P. Payne

Newcastle University - Translational and Clinical Research Institute ( email )

Newcastle upon Tyne
United Kingdom

Adam Harding

University of Oxford - Sir William Dunn School of Pathology ( email )

South Parks Road
Oxford, OX1 3RE
United Kingdom

Tom Tipton

University of Oxford - Wellcome Trust Centre for Human Genetics

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Patpong Rongkard

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Mohammad Ali

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Luisa M. Hering

University of Liverpool - HPRU in Emerging and Zoonotic Infections ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Naomi Meardon

Sheffield Teaching Hospitals NHS Foundation Trust ( email )

Sheffield
United Kingdom

James Austin

University of Liverpool - HPRU in Emerging and Zoonotic Infections

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Rebecca Brown

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease

Medical School
University of Sheffield
Sheffield, S10 2RX
United Kingdom

Donal Skelly

University of Oxford - Nuffield Department of Clinical Neurosciences ( email )

Oxford
United Kingdom

Oxford University Hospitals NHS Foundation Trust ( email )

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

Natalie Gillson

Public Health England Colindale

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

Sue L. Dobson

University of Liverpool - HPRU in Emerging and Zoonotic Infections ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Andrew Cross

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

Gurjinder Sandhar

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease ( email )

Medical School
University of Sheffield
Sheffield, S10 2RX
United Kingdom

Jonathan A. Kilby

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease ( email )

Medical School
University of Sheffield
Sheffield, S10 2RX
United Kingdom

Jessica K. Tyerman

Newcastle University - Translational and Clinical Research Institute ( email )

Newcastle upon Tyne
United Kingdom

Alexander R. Nicols

Newcastle University - Translational and Clinical Research Institute ( email )

Newcastle upon Tyne
United Kingdom

Jarmila S. Spegarova

Newcastle University - Translational and Clinical Research Institute ( email )

Newcastle upon Tyne
United Kingdom

Hema Mehta

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Hailey Hornsby

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease ( email )

Medical School
University of Sheffield
Sheffield, S10 2RX
United Kingdom

Rachel Whitham

Sheffield Teaching Hospitals NHS Foundation Trust ( email )

Sheffield
United Kingdom

Christopher P. Conlon

Government of the United Kingdom - Oxford University Hospitals NHS Foundation Trust

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

Katie Jeffery

Government of the United Kingdom - Oxford University Hospitals NHS Foundation Trust

Philip Goulder

University of Oxford - Department of Paediatrics

United Kingdom

John Frater

University of Oxford - Peter Medawar Building for Pathogen Research ( email )

South Parks Road
OX2 3SY
United Kingdom

Christina Dold

University of Oxford - Oxford Vaccine Group ( email )

Oxford
United Kingdom

Matthew Pace

University of Oxford - Peter Medawar Building for Pathogen Research

Ane Ogbe

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Helen Brown

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Azim M. Ansari

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Emily Adland

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Anthony Brown

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Meera A. Chand

Public Health England Colindale ( email )

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

Adrian Shields

University of Birmingham - Institute of Cancer and Genomic Sciences

Birmingham
United Kingdom

Philippa Matthews

University of Oxford - Peter Medawar Building for Pathogen Research

Susan Hopkins

University of Oxford - NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance ( email )

Oxford
United Kingdom

Public Health England Colindale ( email )

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

Victoria Jane Hall

Public Health England Colindale ( email )

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

University of Oxford - NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance

Oxford
United Kingdom

William James

University of Oxford - Sir William Dunn School of Pathology

South Parks Road
Oxford, OX1 3RE
United Kingdom

Sarah L. Rowland-Jones

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease ( email )

Medical School
University of Sheffield
Sheffield, S10 2RX
United Kingdom

Paul Klenerman

University of Oxford - Peter Medawar Building for Pathogen Research ( email )

South Parks Road
OX2 3SY
United Kingdom

Susanna Dunachie

University of Oxford - Peter Medawar Building for Pathogen Research ( email )

South Parks Road
OX2 3SY
United Kingdom

Alex G. Richter

University of Birmingham - Clinical Immunology Service ( email )

United Kingdom

Christopher J. A. Duncan

Newcastle upon Tyne Hospitals NHS Foundation Trust - Department of Infection and Tropical Medicine ( email )

Newcastle
United Kingdom

Eleanor Barnes

Oxford University Hospitals NHS Foundation Trust

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

Miles W. Carroll

University of Oxford - Wellcome Centre for Human Genetics ( email )

Oxford, OX3 7BN
United Kingdom

Lance Turtle

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

Thushan I. De Silva

Sheffield Teaching Hospitals NHS Foundation Trust - South Yorkshire Regional Department of Infection and Tropical Medicine

17 Mappin Street
Sheffield, S1 4DT
United Kingdom

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease ( email )

Medical School
University of Sheffield
Sheffield, S10 2RX
United Kingdom

No contact information is available for PITCH Consortium

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