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

Summary: 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...

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Main Authors: Adrienn Angyal, PhD, Stephanie Longet, PhD, Shona C Moore, PhD, Rebecca P Payne, DPhil, Adam Harding, MSc, Tom Tipton, PhD, Patpong Rongkard, MSc, Mohammad Ali, MD, Luisa M Hering, MSc, Naomi Meardon, MBChB, James Austin, PhD, Rebecca Brown, PhD, Donal Skelly, PhD, Natalie Gillson, BSc, Sue L Dobson, MSc, Andrew Cross, PhD, Gurjinder Sandhar, MSc, Jonathan A Kilby, MSc, Jessica K Tyerman, BSc, Alexander R Nicols, MSc, Jarmila S Spegarova, PhD, Hema Mehta, DPhil, Hailey Hornsby, MSc, Rachel Whitham, MSc, Christopher P Conlon, ProfPhD, Katie Jeffery, PhD, Philip Goulder, ProfDPhil, John Frater, ProfPhD, Christina Dold, PhD, Matthew Pace, PhD, Ane Ogbe, PhD, Helen Brown, BSc, M Azim Ansari, DPhil, Emily Adland, PhD, Anthony Brown, BSc, Meera Chand, FRCPath, Adrian Shields, PhD, Philippa C Matthews, PhD, Susan Hopkins, PhD, Victoria Hall, PhD, William James, ProfDPhil, Sarah L Rowland-Jones, ProfDM, Paul Klenerman, ProfPhD, Susanna Dunachie, ProfPhD, Alex Richter, ProfPhD, Christopher J A Duncan, DPhil, Eleanor Barnes, ProfPhD, Miles Carroll, ProfPhD, Lance Turtle, PhD, Thushan I de Silva, PhD, Adam Harding, Adam Watson, Adrian Shields, Adrienn Angyal, Ahmed Alhussni, Alex Richter, Alexander Nicols, Alexandra Deeks, Alice Webb-Bridges, Andrew Cross, Ane Ogbe, Anni Jämsén, Anthony Brown, Anu Chawla, Christina Dold, Christopher Duncan, Christopher Conlon, Donal Skelly, Denise O'Donnell, Eleanor Barnes, Emily Adland, Esme Weeks, Gurjinder Sandhar, Hailey Hornsby, Helen Brown, Hema Mehta, Hibatullah Abuelgasim, Huiyuan Xiao, James Austin, Jarmila Spegarova, Jennifer Holmes, Jenny Haworth, Jessica Tyerman, John Frater, Jonathan Kilby, Joseph Cutteridge, Katie Jeffery, Katy Lillie, Lance Turtle, Leigh Romaniuk, Lucy Denly, Luisa Hering, M. Azim Ansari, Matthew Pace, Meera Chand, Miles Carroll, Mohammad Ali, Mwila Kasanyinga, Naomi Meardon, Natalie Gillson, Patpong Rongkard, Paul Klenerman, Philip Goulder, Philippa Matthews, Rachel Whitham, Rebecca Brown, Rebecca Payne, Robert Wilson, Sarah Rowland-Jones, Sarah Thomas, Shona Moore, Siobhan Gardiner, Stephanie Longet, Stephanie Tucker, Sue Dobson, Susan Hopkins, Susanna Dunachie, Syed Adlou, Thushan de Silva, Tom Tipton, Victoria Hall, William James, Allan Lawrie, Nikki Smith, Helena Turton, Amira Zawia, Martin Bayley, Alex Fairman, Kate Harrington, Rosemary Kirk, Louise Marsh, Lisa Watson, Steven Wood, Benjamin Diffey, Chris Jones, Lauren Lett, Gareth Platt, Krishanthi Subramaniam, Daniel Wootton, Brendan Payne, Sophie Hambleton, Sinead Kelly, Judith Marston, Sonia Poolan, Dianne Turner, Muzlifah Haniffa, Emily Stephenson, Sandra Adele, Hossain Delowar Akhter, Senthil Chinnakannan, Catherine de Lara, Timothy Donnison, Carl-Philipp Hackstein, Lian Lee, Nicholas Lim, Tom Malone, Eloise Phillips, Narayan Ramamurthy, Nichola Robinson, Oliver Sampson, David Eyre, Beatrice Simmons, Lizzie Stafford, Alexander Mentzer, Ali Amini, Carolina Arancibia-Cárcamo, Nicholas Provine, Simon Travis, Stavros Dimitriadis, Sile Johnson, Sarah Foulkes, Jameel Khawam, Edgar Wellington, Javier Gilbert-Jaramillo, Michael Knight, Maeva Dupont, Emily Horner, James Thaventhiran, Jeremy Chalk
Format: Article
Language:English
Published: Elsevier 2022-01-01
Series:The Lancet Microbe
Online Access:http://www.sciencedirect.com/science/article/pii/S2666524721002755
_version_ 1819172250564165632
author Adrienn Angyal, PhD
Stephanie Longet, PhD
Shona C Moore, PhD
Rebecca P Payne, DPhil
Adam Harding, MSc
Tom Tipton, PhD
Patpong Rongkard, MSc
Mohammad Ali, MD
Luisa M Hering, MSc
Naomi Meardon, MBChB
James Austin, PhD
Rebecca Brown, PhD
Donal Skelly, PhD
Natalie Gillson, BSc
Sue L Dobson, MSc
Andrew Cross, PhD
Gurjinder Sandhar, MSc
Jonathan A Kilby, MSc
Jessica K Tyerman, BSc
Alexander R Nicols, MSc
Jarmila S Spegarova, PhD
Hema Mehta, DPhil
Hailey Hornsby, MSc
Rachel Whitham, MSc
Christopher P Conlon, ProfPhD
Katie Jeffery, PhD
Philip Goulder, ProfDPhil
John Frater, ProfPhD
Christina Dold, PhD
Matthew Pace, PhD
Ane Ogbe, PhD
Helen Brown, BSc
M Azim Ansari, DPhil
Emily Adland, PhD
Anthony Brown, BSc
Meera Chand, FRCPath
Adrian Shields, PhD
Philippa C Matthews, PhD
Susan Hopkins, PhD
Victoria Hall, PhD
William James, ProfDPhil
Sarah L Rowland-Jones, ProfDM
Paul Klenerman, ProfPhD
Susanna Dunachie, ProfPhD
Alex Richter, ProfPhD
Christopher J A Duncan, DPhil
Eleanor Barnes, ProfPhD
Miles Carroll, ProfPhD
Lance Turtle, PhD
Thushan I de Silva, PhD
Adam Harding
Adam Watson
Adrian Shields
Adrienn Angyal
Ahmed Alhussni
Alex Richter
Alexander Nicols
Alexandra Deeks
Alice Webb-Bridges
Andrew Cross
Ane Ogbe
Anni Jämsén
Anthony Brown
Anu Chawla
Christina Dold
Christopher Duncan
Christopher Conlon
Donal Skelly
Denise O'Donnell
Eleanor Barnes
Emily Adland
Esme Weeks
Gurjinder Sandhar
Hailey Hornsby
Helen Brown
Hema Mehta
Hibatullah Abuelgasim
Huiyuan Xiao
James Austin
Jarmila Spegarova
Jennifer Holmes
Jenny Haworth
Jessica Tyerman
John Frater
Jonathan Kilby
Joseph Cutteridge
Katie Jeffery
Katy Lillie
Lance Turtle
Leigh Romaniuk
Lucy Denly
Luisa Hering
M. Azim Ansari
Matthew Pace
Meera Chand
Miles Carroll
Mohammad Ali
Mwila Kasanyinga
Naomi Meardon
Natalie Gillson
Patpong Rongkard
Paul Klenerman
Philip Goulder
Philippa Matthews
Rachel Whitham
Rebecca Brown
Rebecca Payne
Robert Wilson
Sarah Rowland-Jones
Sarah Thomas
Shona Moore
Siobhan Gardiner
Stephanie Longet
Stephanie Tucker
Sue Dobson
Susan Hopkins
Susanna Dunachie
Syed Adlou
Thushan de Silva
Tom Tipton
Victoria Hall
William James
Allan Lawrie
Nikki Smith
Helena Turton
Amira Zawia
Martin Bayley
Alex Fairman
Kate Harrington
Rosemary Kirk
Louise Marsh
Lisa Watson
Steven Wood
Benjamin Diffey
Chris Jones
Lauren Lett
Gareth Platt
Krishanthi Subramaniam
Daniel Wootton
Brendan Payne
Sophie Hambleton
Sinead Kelly
Judith Marston
Sonia Poolan
Dianne Turner
Muzlifah Haniffa
Emily Stephenson
Sandra Adele
Hossain Delowar Akhter
Senthil Chinnakannan
Catherine de Lara
Timothy Donnison
Carl-Philipp Hackstein
Lian Lee
Nicholas Lim
Tom Malone
Eloise Phillips
Narayan Ramamurthy
Nichola Robinson
Oliver Sampson
David Eyre
Beatrice Simmons
Lizzie Stafford
Alexander Mentzer
Ali Amini
Carolina Arancibia-Cárcamo
Nicholas Provine
Simon Travis
Stavros Dimitriadis
Sile Johnson
Sarah Foulkes
Jameel Khawam
Edgar Wellington
Javier Gilbert-Jaramillo
Michael Knight
Maeva Dupont
Emily Horner
James Thaventhiran
Jeremy Chalk
author_facet Adrienn Angyal, PhD
Stephanie Longet, PhD
Shona C Moore, PhD
Rebecca P Payne, DPhil
Adam Harding, MSc
Tom Tipton, PhD
Patpong Rongkard, MSc
Mohammad Ali, MD
Luisa M Hering, MSc
Naomi Meardon, MBChB
James Austin, PhD
Rebecca Brown, PhD
Donal Skelly, PhD
Natalie Gillson, BSc
Sue L Dobson, MSc
Andrew Cross, PhD
Gurjinder Sandhar, MSc
Jonathan A Kilby, MSc
Jessica K Tyerman, BSc
Alexander R Nicols, MSc
Jarmila S Spegarova, PhD
Hema Mehta, DPhil
Hailey Hornsby, MSc
Rachel Whitham, MSc
Christopher P Conlon, ProfPhD
Katie Jeffery, PhD
Philip Goulder, ProfDPhil
John Frater, ProfPhD
Christina Dold, PhD
Matthew Pace, PhD
Ane Ogbe, PhD
Helen Brown, BSc
M Azim Ansari, DPhil
Emily Adland, PhD
Anthony Brown, BSc
Meera Chand, FRCPath
Adrian Shields, PhD
Philippa C Matthews, PhD
Susan Hopkins, PhD
Victoria Hall, PhD
William James, ProfDPhil
Sarah L Rowland-Jones, ProfDM
Paul Klenerman, ProfPhD
Susanna Dunachie, ProfPhD
Alex Richter, ProfPhD
Christopher J A Duncan, DPhil
Eleanor Barnes, ProfPhD
Miles Carroll, ProfPhD
Lance Turtle, PhD
Thushan I de Silva, PhD
Adam Harding
Adam Watson
Adrian Shields
Adrienn Angyal
Ahmed Alhussni
Alex Richter
Alexander Nicols
Alexandra Deeks
Alice Webb-Bridges
Andrew Cross
Ane Ogbe
Anni Jämsén
Anthony Brown
Anu Chawla
Christina Dold
Christopher Duncan
Christopher Conlon
Donal Skelly
Denise O'Donnell
Eleanor Barnes
Emily Adland
Esme Weeks
Gurjinder Sandhar
Hailey Hornsby
Helen Brown
Hema Mehta
Hibatullah Abuelgasim
Huiyuan Xiao
James Austin
Jarmila Spegarova
Jennifer Holmes
Jenny Haworth
Jessica Tyerman
John Frater
Jonathan Kilby
Joseph Cutteridge
Katie Jeffery
Katy Lillie
Lance Turtle
Leigh Romaniuk
Lucy Denly
Luisa Hering
M. Azim Ansari
Matthew Pace
Meera Chand
Miles Carroll
Mohammad Ali
Mwila Kasanyinga
Naomi Meardon
Natalie Gillson
Patpong Rongkard
Paul Klenerman
Philip Goulder
Philippa Matthews
Rachel Whitham
Rebecca Brown
Rebecca Payne
Robert Wilson
Sarah Rowland-Jones
Sarah Thomas
Shona Moore
Siobhan Gardiner
Stephanie Longet
Stephanie Tucker
Sue Dobson
Susan Hopkins
Susanna Dunachie
Syed Adlou
Thushan de Silva
Tom Tipton
Victoria Hall
William James
Allan Lawrie
Nikki Smith
Helena Turton
Amira Zawia
Martin Bayley
Alex Fairman
Kate Harrington
Rosemary Kirk
Louise Marsh
Lisa Watson
Steven Wood
Benjamin Diffey
Chris Jones
Lauren Lett
Gareth Platt
Krishanthi Subramaniam
Daniel Wootton
Brendan Payne
Sophie Hambleton
Sinead Kelly
Judith Marston
Sonia Poolan
Dianne Turner
Muzlifah Haniffa
Emily Stephenson
Sandra Adele
Hossain Delowar Akhter
Senthil Chinnakannan
Catherine de Lara
Timothy Donnison
Carl-Philipp Hackstein
Lian Lee
Nicholas Lim
Tom Malone
Eloise Phillips
Narayan Ramamurthy
Nichola Robinson
Oliver Sampson
David Eyre
Beatrice Simmons
Lizzie Stafford
Alexander Mentzer
Ali Amini
Carolina Arancibia-Cárcamo
Nicholas Provine
Simon Travis
Stavros Dimitriadis
Sile Johnson
Sarah Foulkes
Jameel Khawam
Edgar Wellington
Javier Gilbert-Jaramillo
Michael Knight
Maeva Dupont
Emily Horner
James Thaventhiran
Jeremy Chalk
author_sort Adrienn Angyal, PhD
collection DOAJ
description Summary: 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 270 373 [IQR 203 461–535 188] antibody units [AU] per mL) were higher than in 111 infection-naive health-care workers following one dose (35 001 [17 099–55 341] AU/mL; p<0·0001) and higher than in 25 infection-naive individuals given two doses (180 904 [108 221–242 467] 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. Funding: UK Department of Health and Social Care, and UK Coronavirus Immunology Consortium.
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spelling doaj.art-d48a073da959456b9ed11417935ce5d72022-12-21T18:14:11ZengElsevierThe Lancet Microbe2666-52472022-01-0131e21e31T-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 studyAdrienn Angyal, PhD0Stephanie Longet, PhD1Shona C Moore, PhD2Rebecca P Payne, DPhil3Adam Harding, MSc4Tom Tipton, PhD5Patpong Rongkard, MSc6Mohammad Ali, MD7Luisa M Hering, MSc8Naomi Meardon, MBChB9James Austin, PhD10Rebecca Brown, PhD11Donal Skelly, PhD12Natalie Gillson, BSc13Sue L Dobson, MSc14Andrew Cross, PhD15Gurjinder Sandhar, MSc16Jonathan A Kilby, MSc17Jessica K Tyerman, BSc18Alexander R Nicols, MSc19Jarmila S Spegarova, PhD20Hema Mehta, DPhil21Hailey Hornsby, MSc22Rachel Whitham, MSc23Christopher P Conlon, ProfPhD24Katie Jeffery, PhD25Philip Goulder, ProfDPhil26John Frater, ProfPhD27Christina Dold, PhD28Matthew Pace, PhD29Ane Ogbe, PhD30Helen Brown, BSc31M Azim Ansari, DPhil32Emily Adland, PhD33Anthony Brown, BSc34Meera Chand, FRCPath35Adrian Shields, PhD36Philippa C Matthews, PhD37Susan Hopkins, PhD38Victoria Hall, PhD39William James, ProfDPhil40Sarah L Rowland-Jones, ProfDM41Paul Klenerman, ProfPhD42Susanna Dunachie, ProfPhD43Alex Richter, ProfPhD44Christopher J A Duncan, DPhil45Eleanor Barnes, ProfPhD46Miles Carroll, ProfPhD47Lance Turtle, PhD48Thushan I de Silva, PhD49Adam HardingAdam WatsonAdrian ShieldsAdrienn AngyalAhmed AlhussniAlex RichterAlexander NicolsAlexandra DeeksAlice Webb-BridgesAndrew CrossAne OgbeAnni JämsénAnthony BrownAnu ChawlaChristina DoldChristopher DuncanChristopher ConlonDonal SkellyDenise O'DonnellEleanor BarnesEmily AdlandEsme WeeksGurjinder SandharHailey HornsbyHelen BrownHema MehtaHibatullah AbuelgasimHuiyuan XiaoJames AustinJarmila SpegarovaJennifer HolmesJenny HaworthJessica TyermanJohn FraterJonathan KilbyJoseph CutteridgeKatie JefferyKaty LillieLance TurtleLeigh RomaniukLucy DenlyLuisa HeringM. Azim AnsariMatthew PaceMeera ChandMiles CarrollMohammad AliMwila KasanyingaNaomi MeardonNatalie GillsonPatpong RongkardPaul KlenermanPhilip GoulderPhilippa MatthewsRachel WhithamRebecca BrownRebecca PayneRobert WilsonSarah Rowland-JonesSarah ThomasShona MooreSiobhan GardinerStephanie LongetStephanie TuckerSue DobsonSusan HopkinsSusanna DunachieSyed AdlouThushan de SilvaTom TiptonVictoria HallWilliam JamesAllan LawrieNikki SmithHelena TurtonAmira ZawiaMartin BayleyAlex FairmanKate HarringtonRosemary KirkLouise MarshLisa WatsonSteven WoodBenjamin DiffeyChris JonesLauren LettGareth PlattKrishanthi SubramaniamDaniel WoottonBrendan PayneSophie HambletonSinead KellyJudith MarstonSonia PoolanDianne TurnerMuzlifah HaniffaEmily StephensonSandra AdeleHossain Delowar AkhterSenthil ChinnakannanCatherine de LaraTimothy DonnisonCarl-Philipp HacksteinLian LeeNicholas LimTom MaloneEloise PhillipsNarayan RamamurthyNichola RobinsonOliver SampsonDavid EyreBeatrice SimmonsLizzie StaffordAlexander MentzerAli AminiCarolina Arancibia-CárcamoNicholas ProvineSimon TravisStavros DimitriadisSile JohnsonSarah FoulkesJameel KhawamEdgar WellingtonJavier Gilbert-JaramilloMichael KnightMaeva DupontEmily HornerJames ThaventhiranJeremy ChalkDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UKWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UKHealth Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UKTranslational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, Newcastle, UKSir William Dunn School of Pathology, Division of Medical Sciences, University of Oxford, Oxford, UKWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Centre For Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, ThailandPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Centre For Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UKHealth Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UKSheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UKHealth Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UKDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UKPublic Health England, Colindale, London, UKHealth Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UKDepartment of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UKDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UKDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UKTranslational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, Newcastle, UKTranslational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, Newcastle, UKTranslational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, Newcastle, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UKDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UKSheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UKOxford University Hospitals NHS Foundation Trust, Oxford, UKRadcliffe Department of Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UKPeter Medawar Building for Pathogen Research, Department of Paediatrics, University of Oxford, Oxford, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UKOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UKPeter Medawar Building for Pathogen Research, Department of Paediatrics, University of Oxford, Oxford, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UKPublic Health England, Colindale, London, UKInstitute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UKNIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, University of Oxford, Oxford, UK; Public Health England, Colindale, London, UK; Faculty of Medicine, Department of Infectious Disease, Imperial College London, London, UKNIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, University of Oxford, Oxford, UK; Public Health England, Colindale, London, UKSir William Dunn School of Pathology, Division of Medical Sciences, University of Oxford, Oxford, UKDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Centre For Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Correspondence to: Prof Susanna Dunachie, Peter Medawar Building for Pathogen Research, Oxford OX1 3SY, UKInstitute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKTranslational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, Newcastle, UK; Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UKWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UKHealth Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust, member of Liverpool Health Partners, Liverpool, UKDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK; Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UKSummary: 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 270 373 [IQR 203 461–535 188] antibody units [AU] per mL) were higher than in 111 infection-naive health-care workers following one dose (35 001 [17 099–55 341] AU/mL; p<0·0001) and higher than in 25 infection-naive individuals given two doses (180 904 [108 221–242 467] 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. Funding: UK Department of Health and Social Care, and UK Coronavirus Immunology Consortium.http://www.sciencedirect.com/science/article/pii/S2666524721002755
spellingShingle Adrienn Angyal, PhD
Stephanie Longet, PhD
Shona C Moore, PhD
Rebecca P Payne, DPhil
Adam Harding, MSc
Tom Tipton, PhD
Patpong Rongkard, MSc
Mohammad Ali, MD
Luisa M Hering, MSc
Naomi Meardon, MBChB
James Austin, PhD
Rebecca Brown, PhD
Donal Skelly, PhD
Natalie Gillson, BSc
Sue L Dobson, MSc
Andrew Cross, PhD
Gurjinder Sandhar, MSc
Jonathan A Kilby, MSc
Jessica K Tyerman, BSc
Alexander R Nicols, MSc
Jarmila S Spegarova, PhD
Hema Mehta, DPhil
Hailey Hornsby, MSc
Rachel Whitham, MSc
Christopher P Conlon, ProfPhD
Katie Jeffery, PhD
Philip Goulder, ProfDPhil
John Frater, ProfPhD
Christina Dold, PhD
Matthew Pace, PhD
Ane Ogbe, PhD
Helen Brown, BSc
M Azim Ansari, DPhil
Emily Adland, PhD
Anthony Brown, BSc
Meera Chand, FRCPath
Adrian Shields, PhD
Philippa C Matthews, PhD
Susan Hopkins, PhD
Victoria Hall, PhD
William James, ProfDPhil
Sarah L Rowland-Jones, ProfDM
Paul Klenerman, ProfPhD
Susanna Dunachie, ProfPhD
Alex Richter, ProfPhD
Christopher J A Duncan, DPhil
Eleanor Barnes, ProfPhD
Miles Carroll, ProfPhD
Lance Turtle, PhD
Thushan I de Silva, PhD
Adam Harding
Adam Watson
Adrian Shields
Adrienn Angyal
Ahmed Alhussni
Alex Richter
Alexander Nicols
Alexandra Deeks
Alice Webb-Bridges
Andrew Cross
Ane Ogbe
Anni Jämsén
Anthony Brown
Anu Chawla
Christina Dold
Christopher Duncan
Christopher Conlon
Donal Skelly
Denise O'Donnell
Eleanor Barnes
Emily Adland
Esme Weeks
Gurjinder Sandhar
Hailey Hornsby
Helen Brown
Hema Mehta
Hibatullah Abuelgasim
Huiyuan Xiao
James Austin
Jarmila Spegarova
Jennifer Holmes
Jenny Haworth
Jessica Tyerman
John Frater
Jonathan Kilby
Joseph Cutteridge
Katie Jeffery
Katy Lillie
Lance Turtle
Leigh Romaniuk
Lucy Denly
Luisa Hering
M. Azim Ansari
Matthew Pace
Meera Chand
Miles Carroll
Mohammad Ali
Mwila Kasanyinga
Naomi Meardon
Natalie Gillson
Patpong Rongkard
Paul Klenerman
Philip Goulder
Philippa Matthews
Rachel Whitham
Rebecca Brown
Rebecca Payne
Robert Wilson
Sarah Rowland-Jones
Sarah Thomas
Shona Moore
Siobhan Gardiner
Stephanie Longet
Stephanie Tucker
Sue Dobson
Susan Hopkins
Susanna Dunachie
Syed Adlou
Thushan de Silva
Tom Tipton
Victoria Hall
William James
Allan Lawrie
Nikki Smith
Helena Turton
Amira Zawia
Martin Bayley
Alex Fairman
Kate Harrington
Rosemary Kirk
Louise Marsh
Lisa Watson
Steven Wood
Benjamin Diffey
Chris Jones
Lauren Lett
Gareth Platt
Krishanthi Subramaniam
Daniel Wootton
Brendan Payne
Sophie Hambleton
Sinead Kelly
Judith Marston
Sonia Poolan
Dianne Turner
Muzlifah Haniffa
Emily Stephenson
Sandra Adele
Hossain Delowar Akhter
Senthil Chinnakannan
Catherine de Lara
Timothy Donnison
Carl-Philipp Hackstein
Lian Lee
Nicholas Lim
Tom Malone
Eloise Phillips
Narayan Ramamurthy
Nichola Robinson
Oliver Sampson
David Eyre
Beatrice Simmons
Lizzie Stafford
Alexander Mentzer
Ali Amini
Carolina Arancibia-Cárcamo
Nicholas Provine
Simon Travis
Stavros Dimitriadis
Sile Johnson
Sarah Foulkes
Jameel Khawam
Edgar Wellington
Javier Gilbert-Jaramillo
Michael Knight
Maeva Dupont
Emily Horner
James Thaventhiran
Jeremy Chalk
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
The Lancet Microbe
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url http://www.sciencedirect.com/science/article/pii/S2666524721002755
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