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Sustained T Cell Immunity, Protection and Boosting Using Extended Dosing Intervals of BNT162b2 mRNA Vaccine

93 Pages Posted: 21 Jul 2021 Publication Status: Published

See all articles by Rebecca P. Payne

Rebecca P. Payne

Newcastle University - Translational and Clinical Research Institute Immunity and Inflammation Theme

Stephanie Longet

University of Oxford - Wellcome Trust Centre for Human Genetics

James A. Austin

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

Donal Skelly

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

Wanwisa Dejnirattisai

University of Oxford - Wellcome Centre for Human Genetics

Sandra Adele

University of Oxford - Peter Medawar Building for Pathogen Research

Naomi Meardon

Sheffield Teaching Hospitals NHS Foundation Trust

Sian Faustini

University of Birmingham - Institute of Cancer and Genomic Sciences; University of Birmingham - Clinical Immunology Service

Saly Al-Taei

University of Birmingham - Institute of Cancer and Genomic Science

Shona Moore

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

Tom Tipton

University of Oxford - Wellcome Trust Centre for Human Genetics

Luisa M. Hering

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

Adrienn Angyal

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

Rebecca Brown

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

Natalie Gillson

Public Health England Colindale

Sue L. Dobson

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

Ali Amini

Oxford University Hospitals NHS Foundation Trust

Piyada Supasa

University of Oxford - Wellcome Centre for Human Genetics

Andrew Cross

Newcastle University - Translational and Clinical Research Institute Immunity and Inflammation Theme

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 Immunity and Inflammation Theme

Alexander R. Nicols

Newcastle University - Translational and Clinical Research Institute Immunity and Inflammation Theme

Thomas Altmann

Newcastle University - Translational and Clinical Research Institute Immunity and Inflammation Theme

Hailey Hornsby

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

Rachel Whitham

Sheffield Teaching Hospitals NHS Foundation Trust

Eloise Phillips

University of Oxford - Peter Medawar Building for Pathogen Research

Tom Malone

University of Oxford - Peter Medawar Building for Pathogen Research

Alexander Hargreaves

University of Oxford

Adrian Shields

University Hospitals Birmingham NHS Foundation Trust

Ayoub Saei

Public Health England Colindale

Sarah Foulkes

Public Health England Colindale

Lizzie Stafford

Oxford University Hospitals NHS Foundation Trust

Síle Johnson

University of Oxford - Peter Medawar Building for Pathogen Research

Dan G. Wootton

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

Christopher P. Conlon

Oxford University Hospitals NHS Foundation Trust

Katie Jeffery

Oxford University Hospitals NHS Foundation Trust

Philippa Matthews

University of Oxford - Peter Medawar Building for Pathogen Research

John Frater

University of Oxford - Peter Medawar Building for Pathogen Research

Alexandra Deeks

University of Oxford - Peter Medawar Building for Pathogen Research

Christina Dold

University of Oxford - Oxford Vaccine Group

Andrew J. Pollard

University of Oxford - Centre for Vaccinology and Tropical Medicine

Anthony Brown

University of Oxford - Peter Medawar Building for Pathogen Research

Sarah L. Rowland-Jones

Sheffield Teaching Hospitals NHS Foundation Trust

Juthathip Mongkolsapaya

University of Oxford - Wellcome Trust Centre for Human Genetics

Eleanor Barnes

Oxford University Hospitals NHS Foundation Trust

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

Christopher J. A. Duncan

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

Alex G. Richter

University of Birmingham - Institute of Cancer and Genomic Sciences; University of Birmingham - Clinical Immunology Service

Miles W. Carroll

University of Oxford - Wellcome Centre for Human Genetics

Gavin R. Screaton

University of Oxford - Wellcome Centre for Human Genetics

Thushan I. de Silva

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

Lance Turtle

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

Paul Klenerman

University of Oxford - Peter Medawar Building for Pathogen Research

Susanna Dunachie

University of Oxford - Peter Medawar Building for Pathogen Research

The PITCH Consortium

Independent

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Abstract

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the UK to accelerate population coverage with a single dose. In a study of 503 healthcare workers, we show that after priming following the first vaccine there is a marked decline in SARS-CoV-2 neutralizing antibody (NAb) levels, but, in contrast, a sustained T cell response to spike protein. This divergent immune profile was accompanied by robust protection from infection over this period from the circulating alpha (B.1.1.7) variant. Importantly, following the second vaccine dose, NAb levels were higher after the extended dosing interval (6-14 weeks) compared to the conventional 3-4 week regimen, accompanied by a clear enrichment of CD4+ T cells expressing IL2. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective, immunogenic protocol and that antiviral T cell responses are a potential mechanism of protection.

Trial Registration Details: PITCH is a sub-study of the SIREN study which is registered with ISRCTN, number ISRCTN11041050,

Funding Information: This work was funded by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to Covid-19 in Health workers) Consortium, with contributions from UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC), the Huo Family Foundation and The National Institute for Health Research (UKRIDHSC COVID-19 Rapid Response Rolling Call, Grant Reference Number COV19-RECPLAS).EB and PK are NIHR Senior Investigators and PK is funded by WT109965MA. SJD is funded by an NIHR Global Research Professorship (NIHR300791). TdS is funded by a Wellcome Trust Intermediate Clinical Fellowship (110058/Z/15/Z). RPP is funded by a Career Re-entry Fellowship (204721/Z/16/Z). CJAD is funded by a Wellcome Clinical Research Career Development Fellowship (211153/Z/18/Z). DS is supported by the NIHR Academic Clinical Lecturer programme in Oxford. LT is supported by the Wellcome Trust (grant number 205228/Z/16/Z) and the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections (NIHR200907) at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. DGW is supported by an NIHR Advanced Fellowship in Liverpool. LT and MC are supported by U.S. Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085.

Declaration of Interests: AJP is Chair of UK Dept. Health and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI), but does not participate in policy decisions on COVID-19 vaccines. He is a member of the WHO’s SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. AJP is chief investigator on clinical trials of Oxford University’s COVID-19 vaccine funded by NIHR. Oxford University has entered a joint COVID-19 vaccine development partnership with AstraZeneca.

Ethics Approval Statement: PITCH is a sub-study of the SIREN study which was approved by the Berkshire Research Ethics Committee, Health Research 250 Authority (IRAS ID 284460, REC reference 20/SC/0230), with PITCH recognised as a sub-study on 2 December 2020. SIREN is registered with ISRCTN (Trial ID:252 ISRCTN11041050). Some participants were recruited under aligned study protocols. In Birmingham participants were recruited under the Determining the immune response to SARS-CoV-2 infection in convalescent health care workers (COCO) study (IRAS ID: 282525). 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 8 March 2016, and amended on 14th September 2020 and 4th May 2021. In Oxford, participants were recruited under the GI Biobank Study 16/YH/0247, approved by the research ethics committee (REC) at Yorkshire & The Humber - Sheffield Research Ethics Committee on 29 July 2016, which has been amended for this purpose on 8 June 2020. In Sheffield, participants were recruited under the Observational Biobanking study STHObs (18/YH/0441), which was amended for this study on 10 September 2020. The study was conducted in compliance with all relevant ethical regulations for work with human participants, and according to the principles of the Declaration of Helsinki (2008) and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. Written informed consent was obtained for all patients enrolled in the study.

Suggested Citation

Payne, Rebecca P. and Longet, Stephanie and Austin, James A. and Skelly, Donal and Skelly, Donal and Dejnirattisai, Wanwisa and Adele, Sandra and Meardon, Naomi and Faustini, Sian and Al-Taei, Saly and Moore, Shona and Tipton, Tom and Hering, Luisa M. and Angyal, Adrienn and Brown, Rebecca and Gillson, Natalie and Dobson, Sue L. and Amini, Ali and Supasa, Piyada and Cross, Andrew and Sandhar, Gurjinder and Kilby, Jonathan A. and Tyerman, Jessica K. and Nicols, Alexander R. and Altmann, Thomas and Hornsby, Hailey and Whitham, Rachel and Phillips, Eloise and Malone, Tom and Hargreaves, Alexander and Shields, Adrian and Saei, Ayoub and Foulkes, Sarah and Stafford, Lizzie and Johnson, Síle and Wootton, Dan G. and Conlon, Christopher P. and Jeffery, Katie and Matthews, Philippa and Frater, John and Deeks, Alexandra and Dold, Christina and Pollard, Andrew J. and Brown, Anthony and Rowland-Jones, Sarah L. and Mongkolsapaya, Juthathip and Barnes, Eleanor and Hopkins, Susan and Hall, Victoria Jane and Duncan, Christopher J. A. and Richter, Alex G. and Carroll, Miles W. and Screaton, Gavin R. and de Silva, Thushan I. and Turtle, Lance and Klenerman, Paul and Dunachie, Susanna and Consortium, The PITCH, Sustained T Cell Immunity, Protection and Boosting Using Extended Dosing Intervals of BNT162b2 mRNA Vaccine. Available at SSRN: https://ssrn.com/abstract=3891065 or http://dx.doi.org/10.2139/ssrn.3891065
This version of the paper has not been formally peer reviewed.

Rebecca P. Payne

Newcastle University - Translational and Clinical Research Institute Immunity and Inflammation Theme ( email )

Newcastle upon Tyne
United Kingdom

Stephanie Longet

University of Oxford - Wellcome Trust Centre for Human Genetics

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

James A. Austin

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Donal Skelly

Oxford University Hospitals NHS Foundation Trust ( email )

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

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

Oxford
United Kingdom

Wanwisa Dejnirattisai

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

Oxford, OX3 7BN
United Kingdom

Sandra Adele

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

South Parks Road
OX2 3SY
United Kingdom

Naomi Meardon

Sheffield Teaching Hospitals NHS Foundation Trust ( email )

Sheffield
United Kingdom

Sian Faustini

University of Birmingham - Institute of Cancer and Genomic Sciences

Birmingham
United Kingdom

University of Birmingham - Clinical Immunology Service ( email )

United Kingdom

Saly Al-Taei

University of Birmingham - Institute of Cancer and Genomic Science

Edgbaston, B15 2TT
United Kingdom

Shona Moore

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections ( email )

Ronald Ross Building
8 West Derby Street
Liverpool, L69 7BE
United Kingdom

Tom Tipton

University of Oxford - Wellcome Trust Centre for Human Genetics

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

Luisa M. Hering

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Adrienn Angyal

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

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

Rebecca Brown

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

17 Mappin Street
Sheffield, S1 4DT
United Kingdom

Natalie Gillson

Public Health England Colindale

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

Sue L. Dobson

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Ali Amini

Oxford University Hospitals NHS Foundation Trust

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

Piyada Supasa

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

Oxford, OX3 7BN
United Kingdom

Andrew Cross

Newcastle University - Translational and Clinical Research Institute Immunity and Inflammation Theme

Newcastle upon Tyne
United Kingdom

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 Immunity and Inflammation Theme ( email )

Newcastle upon Tyne
United Kingdom

Alexander R. Nicols

Newcastle University - Translational and Clinical Research Institute Immunity and Inflammation Theme ( email )

Newcastle upon Tyne
United Kingdom

Thomas Altmann

Newcastle University - Translational and Clinical Research Institute Immunity and Inflammation Theme

Newcastle upon Tyne
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

Eloise Phillips

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

South Parks Road
OX2 3SY
United Kingdom

Tom Malone

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

South Parks Road
OX2 3SY
United Kingdom

Alexander Hargreaves

University of Oxford ( email )

The Wellcome Centre of Human Genetics
Roosevelt Drive
Oxford, OX3 7BN
United Kingdom

Adrian Shields

University Hospitals Birmingham NHS Foundation Trust

Mindelsohn Way
Edgbaston
Birmingham, B15 2TH
United Kingdom

Ayoub Saei

Public Health England Colindale ( email )

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

Sarah Foulkes

Public Health England Colindale ( email )

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

Lizzie Stafford

Oxford University Hospitals NHS Foundation Trust ( email )

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

Síle Johnson

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

South Parks Road
OX2 3SY
United Kingdom

Dan G. Wootton

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

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Christopher P. Conlon

Oxford University Hospitals NHS Foundation Trust

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

Katie Jeffery

Oxford University Hospitals NHS Foundation Trust

Philippa Matthews

University of Oxford - Peter Medawar Building for Pathogen Research

John Frater

University of Oxford - Peter Medawar Building for Pathogen Research

Alexandra Deeks

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Christina Dold

University of Oxford - Oxford Vaccine Group ( email )

Oxford
United Kingdom

Andrew J. Pollard

University of Oxford - Centre for Vaccinology and Tropical Medicine ( email )

Oxford
United Kingdom

Anthony Brown

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Sarah L. Rowland-Jones

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield
United Kingdom

Juthathip Mongkolsapaya

University of Oxford - Wellcome Trust Centre for Human Genetics

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

Eleanor Barnes

Oxford University Hospitals NHS Foundation Trust

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

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

Christopher J. A. Duncan

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

Newcastle
United Kingdom

Alex G. Richter

University of Birmingham - Institute of Cancer and Genomic Sciences ( email )

Edgbaston
Birminham, Birmingham B152TT
United Kingdom

University of Birmingham - Clinical Immunology Service ( email )

United Kingdom

Miles W. Carroll

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

Oxford, OX3 7BN
United Kingdom

Gavin R. Screaton

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

Oxford, OX3 7BN
United Kingdom

Thushan I. De Silva

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

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

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

17 Mappin Street
Sheffield, S1 4DT
United Kingdom

Lance Turtle

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

Paul Klenerman (Contact Author)

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

The PITCH Consortium

Independent ( email )

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