puc-header

Evolution of Long-Term Hybrid Immunity in Healthcare Workers after Different Covid-19 Vaccination Regimens: A Longitudinal Observational Cohort Study

56 Pages Posted: 8 Aug 2022 Publication Status: Published

See all articles by Shona C. Moore

Shona C. Moore

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

Barbara Kronsteiner

University of Oxford - Peter Medawar Building for Pathogen Research

Stephanie Longet

University of Oxford - Wellcome Trust Centre for Human Genetics

Sandra Adele

University of Oxford - Peter Medawar Building for Pathogen Research

Alexandra Deeks

University of Oxford - Peter Medawar Building for Pathogen Research

Chang Liu

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

Wanwisa Dejnirattisai

University of Oxford - Wellcome Trust Centre for Human Genetics

Laura Silva Reyes

University of Oxford - Oxford Vaccine Group

Naomi Meardon

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease; Sheffield Teaching Hospitals NHS Foundation Trust

Sian Faustini

University of Birmingham - Clinical Immunology Service

Saly Al-Taei

University of Birmingham - Institute of Cancer and Genomic Science

Tom Tipton

University of Oxford - Pandemic Sciences Institute

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 & Cardiovascular Disease

Alexander R. Nicols

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

Sue L. Dobson

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

Piyada Supasa

University of Oxford - Wellcome Trust Centre for Human Genetics

Aekkachai Tuekprakhon

University of Oxford - Wellcome Trust Centre for Human Genetics

Andrew Cross

NHS Foundation Trust - Liverpool University Hospitals NHS Foundation Trust (LUH)

Jessica K. Tyerman

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

Hailey Hornsby

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

Irina Grouneva

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

Megan Plowright

Dept Infection, Immunity & Cardiovascular Disease, University of Sheffield

Peijun Zhang

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

Thomas Newman

Dept of Infectious Diseases & Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust

Jeremy M. Nell

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

Priyanka Abraham

University of Oxford - Peter Medawar Building for Pathogen Research

Mohammad Ali

University of Oxford - Peter Medawar Building for Pathogen Research

Tom Malone

University of Oxford - Peter Medawar Building for Pathogen Research

Isabel Neale

University of Oxford - Peter Medawar Building for Pathogen Research

Eloise Phillips

University of Oxford - Peter Medawar Building for Pathogen Research

Joseph D. Wilson

University of Oxford - Peter Medawar Building for Pathogen Research

Sam M. Murray

University of Oxford - Peter Medawar Building for Pathogen Research

Adrian Shields

University of Birmingham - Institute of Immunology and Immunotherapy

Emily C. Horner

University of Cambridge - MRC Toxicology Unit

Lucy H. Booth

University of Cambridge - MRC Toxicology Unit

Lizzie Stafford

Oxford University Hospitals NHS Foundation Trust

Sagida Bibi

University of Oxford - Centre for Vaccinology and Tropical Medicine

Dan G. Wootton

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

Alexander J. Mentzer

University of Oxford - Wellcome Centre for Human Genetics; University of Oxford - Li Ka Shing Centre for Health Information and Discovery

Christopher P. Conlon

Oxford University Hospitals NHS Foundation Trust

Katie Jeffery

Oxford University Hospitals NHS Foundation Trust

Philippa C. Matthews

University of Oxford - Peter Medawar Building for Pathogen Research

Andrew J. Pollard

University of Oxford - Oxford Vaccine Group

Anthony Brown

University of Oxford - Peter Medawar Building for Pathogen Research

Sarah L. Rowland-Jones

Sheffield Teaching Hospitals NHS Foundation Trust

Juthathip Mongkolspaya

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

Rebecca P. Payne

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

Christina Dold

University of Oxford - Oxford Vaccine Group

Teresa Lambe

University of Oxford - Centre for Vaccinology and Tropical Medicine

James Thaventhiran

University of Cambridge - MRC Toxicology Unit

Gavin R. Screaton

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

Eleanor Barnes

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

Christopher JA Duncan

Newcastle University - Translational and Clinical Research Institute

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 Trust Centre for Human Genetics; University of Oxford - Pandemic Sciences Institute

Thushan I. de Silva

University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease; University of Sheffield - The Florey Institute for Host-Pathogen Interactions; London School of Hygiene & Tropical Medicine - Vaccines and Immunity Theme

Paul Klenerman

University of Oxford - Nuffield Department of Clinical Medicine

Susanna Dunachie

Mahidol University - Mahidol-Oxford Tropical Medicine Research Unit

Lance Turtle

University of Liverpool - NIHR Health Protection Research Unit for Emerging and Zoonotic Infection

PITCH Consortium

Independent

More...

Abstract

Both infection and vaccination, alone or in combination, generate antibody and T cell responses against SARS-CoV-2. However, the maintenance of such responses – and hence protection from disease – requires careful characterisation. In a large prospective study of UK healthcare workers (Protective immunity from T cells in Healthcare workers (PITCH), within the larger SARS-CoV-2 immunity & reinfection evaluation (SIREN) study) we previously observed that prior infection impacted strongly on subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. Here, we report longer follow up of 684 HCWs in this cohort over 6-9 months following two doses of BNT162b2 or AZ1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination. We make three observations: Firstly, the dynamics of humoral and cellular responses differ; binding and neutralising antibodies declined whereas T and memory B cell responses were maintained after the second vaccine dose. Secondly, vaccine boosting restored IgG levels, broadened neutralising activity against variants of concern including omicron BA.1, BA.2 and BA.5, and further boosted T cell responses. Thirdly, prior infection maintained its impact driving larger as well as broader T cell responses compared with never-infected people – a feature maintained even after the third dose. In conclusion, broadly cross-reactive T cell responses are well maintained over time – especially in those with “hybrid” vaccine and infection-induced immunity – and may contribute to continued protection against severe disease.

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, UKRI as part of “Investigation of proven vaccine breakthrough by SARS-CoV-2 variants in established UK healthcare worker cohorts: SIREN consortium & PITCH Plus Pathway” MR/W02067X/1, 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).

Declaration of Interests: S.J.D. is a Scientific Advisor to the Scottish Parliament on COVID-19 for which she receives a fee. A.J.P. 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 was previously 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. G.S. sits on the GSK Vaccines Scientific Advisory Board and is a founder member of RQ Biotechnology. All other authors have nothing to declare.

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. We also included some participants from Cambridge from a study approved by the National Research Ethics Committee and Health Research Authority (East of England – Cambridge Research Ethics Committee (SCORPIO study, SARS-CoV-2 vaccination response in obesity amendment of ‘‘NIHR BioResource’’ 17/EE/0025).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 participants enrolled in the study.

Keywords: SARS-CoV-2, COVID-19, COVID vaccine, T cells, antibody, immunity

Suggested Citation

Moore, Shona C. and Kronsteiner, Barbara and Longet, Stephanie and Adele, Sandra and Deeks, Alexandra and Liu, Chang and Dejnirattisai, Wanwisa and Silva Reyes, Laura and Meardon, Naomi and Faustini, Sian and Al-Taei, Saly and Tipton, Tom and Hering, Luisa M. and Angyal, Adrienn and Brown, Rebecca and Nicols, Alexander R. and Dobson, Sue L. and Supasa, Piyada and Tuekprakhon, Aekkachai and Cross, Andrew and Tyerman, Jessica K. and Hornsby, Hailey and Grouneva, Irina and Plowright, Megan and Zhang, Peijun and Newman, Thomas and Nell, Jeremy M. and Abraham, Priyanka and Ali, Mohammad and Malone, Tom and Neale, Isabel and Phillips, Eloise and Wilson, Joseph D. and Murray, Sam M. and Shields, Adrian and Horner, Emily C. and Booth, Lucy H. and Stafford, Lizzie and Bibi, Sagida and Wootton, Dan G. and Mentzer, Alexander J. and Conlon, Christopher P. and Jeffery, Katie and Matthews, Philippa C. and Pollard, Andrew J. and Brown, Anthony and Rowland-Jones, Sarah L. and Mongkolspaya, Juthathip and Payne, Rebecca P. and Dold, Christina and Lambe, Teresa and Thaventhiran, James and Screaton, Gavin R. and Barnes, Eleanor and Hopkins, Susan and Hall, Victoria Jane and Duncan, Christopher JA and Richter, Alex G. and Carroll, Miles W. and de Silva, Thushan I. and Klenerman, Paul and Dunachie, Susanna and Turtle, Lance and Consortium, PITCH, Evolution of Long-Term Hybrid Immunity in Healthcare Workers after Different Covid-19 Vaccination Regimens: A Longitudinal Observational Cohort Study. Available at SSRN: https://ssrn.com/abstract=4180810 or http://dx.doi.org/10.2139/ssrn.4180810
This version of the paper has not been formally peer reviewed.

Shona C. Moore (Contact Author)

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences ( email )

United Kingdom

Barbara Kronsteiner

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

South Parks Road
OX2 3SY
United Kingdom

Stephanie Longet

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

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

Sandra Adele

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

South Parks Road
OX2 3SY
United Kingdom

Alexandra Deeks

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Chang Liu

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI) ( email )

Wanwisa Dejnirattisai

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

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

Laura Silva Reyes

University of Oxford - Oxford Vaccine Group ( email )

United Kingdom

Naomi Meardon

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

Sheffield Teaching Hospitals NHS Foundation Trust ( email )

Sheffield
United Kingdom

Sian Faustini

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

Tom Tipton

University of Oxford - Pandemic Sciences Institute ( email )

United Kingdom

Luisa M. Hering

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

Chatham Street
Brownlow Hill
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 & Cardiovascular Disease ( email )

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

Alexander R. Nicols

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

Newcastle upon Tyne
United Kingdom

Sue L. Dobson

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

Chatham Street
Brownlow Hill
Liverpool, L69 7ZA
United Kingdom

Piyada Supasa

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

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

Aekkachai Tuekprakhon

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

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

Andrew Cross

NHS Foundation Trust - Liverpool University Hospitals NHS Foundation Trust (LUH) ( email )

United Kingdom

Jessica K. Tyerman

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

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

Irina Grouneva

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

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

Megan Plowright

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

Peijun Zhang

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

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

Thomas Newman

Dept of Infectious Diseases & Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust ( email )

United Kingdom

Jeremy M. Nell

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

United Kingdom

Priyanka Abraham

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

South Parks Road
OX2 3SY
United Kingdom

Mohammad Ali

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

Isabel Neale

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

South Parks Road
OX2 3SY
United Kingdom

Eloise Phillips

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

South Parks Road
OX2 3SY
United Kingdom

Joseph D. Wilson

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

South Parks Road
OX2 3SY
United Kingdom

Sam M. Murray

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

South Parks Road
OX2 3SY
United Kingdom

Adrian Shields

University of Birmingham - Institute of Immunology and Immunotherapy ( email )

Birmingham
United Kingdom

Emily C. Horner

University of Cambridge - MRC Toxicology Unit ( email )

United Kingdom

Lucy H. Booth

University of Cambridge - MRC Toxicology Unit ( email )

United Kingdom

Lizzie Stafford

Oxford University Hospitals NHS Foundation Trust ( email )

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

Sagida Bibi

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

Oxford
United Kingdom

Dan G. Wootton

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

Chatham Street
Brownlow Hill
Liverpool, L69 7ZA
United Kingdom

Alexander J. Mentzer

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

University of Oxford - Li Ka Shing Centre for Health Information and Discovery ( email )

Oxford, OX3 7FZ
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 C. Matthews

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

South Parks Road
OX2 3SY
United Kingdom

Andrew J. Pollard

University of Oxford - Oxford Vaccine Group ( email )

Anthony Brown

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

South Parks Road
OX2 3SY
United Kingdom

Sarah L. Rowland-Jones

Sheffield Teaching Hospitals NHS Foundation Trust ( email )

Robert Hadfield Building
Northern General Hospital
Sheffield, S5 7AU
United Kingdom

Juthathip Mongkolspaya

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI) ( email )

Rebecca P. Payne

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

Newcastle upon Tyne
United Kingdom

Christina Dold

University of Oxford - Oxford Vaccine Group ( email )

Oxford
United Kingdom

Teresa Lambe

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

Oxford
United Kingdom

James Thaventhiran

University of Cambridge - MRC Toxicology Unit ( email )

Gavin R. Screaton

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI) ( email )

Eleanor Barnes

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

South Parks Road
OX2 3SY
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 JA Duncan

Newcastle University - Translational and Clinical Research Institute ( email )

Newcastle upon Tyne
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 )

Birmingham
United Kingdom

Miles W. Carroll

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

University of Oxford - Pandemic Sciences Institute ( email )

United Kingdom

Thushan I. De Silva

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

University of Sheffield - The Florey Institute for Host-Pathogen Interactions ( email )

London School of Hygiene & Tropical Medicine - Vaccines and Immunity Theme ( email )

Paul Klenerman

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

Oxford
United Kingdom

Susanna Dunachie

Mahidol University - Mahidol-Oxford Tropical Medicine Research Unit ( email )

Lance Turtle

University of Liverpool - NIHR Health Protection Research Unit for Emerging and Zoonotic Infection

PITCH Consortium

Independent

Click here to go to Cell.com

Paper statistics

Downloads
18
Abstract Views
615
PlumX Metrics