Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

PITCH Consortium

doi:10.1016/j.cell.2021.10.011

Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

PITCH Consortium

Research output: Contribution to journal › Article › peer-review

235 Citations (Scopus)

30 Downloads (Pure)

Abstract

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4⁺ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.

Original language	English
Article number	e11
Pages (from-to)	5699-5714
Number of pages	28
Journal	Cell
Volume	184
Issue number	23
Early online date	16 Oct 2021
DOIs	https://doi.org/10.1016/j.cell.2021.10.011
Publication status	Published - 11 Nov 2021

Bibliographical note

Funding Information: We are grateful to all our healthcare worker colleagues who participated in the study. For the Birmingham participants, the study was carried out at the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. Laboratory studies were undertaken by the Clinical Immunology Service, University of Birmingham. This work was funded by the United Kingdom Department of Health and Social Care as part of the PITCH 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 COV19-RECPLAS ). A. Amini is funded by a Wellcome clinical research training fellowship ( 216417/Z/19/Z ). E.B. and P.K. are NIHR Senior Investigators, and P.K. is funded by WT109965MA . S.D. is funded by an NIHR global research professorship ( NIHR300791 ). T.I.d.S is funded by a Wellcome Trust intermediate clinical fellowship ( 110058/Z/15/Z ). R.P.P. is funded by a career re-entry fellowship ( 204721/Z/16/Z ). C.J.A.D. is funded by a Wellcome clinical research career development fellowship ( 211153/Z/18/Z ). D.S. is supported by the NIHR Academic Clinical Lecturer Program in Oxford. L.T. is supported by the Wellcome Trust (grant 205228/Z/16/Z ) and the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections ( NIHR200907 ) at the University of Liverpool in partnership with Public Health England (PHE) in collaboration with the Liverpool School of Tropical Medicine and the University of Oxford . D.G.W. is supported by an NIHR advanced fellowship in Liverpool. M.C., A.H., S.L., L.T., and T.T. are supported by US Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085 . The Sheffield Teaching Hospitals Observational Study of Patients with Pulmonary Hypertension, Cardiovascular and other Respiratory Diseases (STH-ObS) was supported by the British Heart Foundation ( PG/11/116/29288 ). The STH-ObS Chief Investigator Allan Laurie is supported by a British Heart Foundation Senior Basic Science Research fellowship ( FS/18/52/33808 ). We gratefully acknowledge financial support from the UK Department of Health via the Sheffield NIHR Clinical Research Facility award to the Sheffield Teaching Hospitals Foundation NHS Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care or Public Health England, or the US Food and Drug Administration.

A.J.P. is Chair of the United Kingdom Department of Health and Social Care (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 the DHSC, JCVI, or WHO. A.J.P. 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.

Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Publisher Copyright: © 2021 The Author(s). Published by Elsevier Inc.

Citation: Rebecca P. Payne, Stephanie Longet, James A. Austin, Donal T. Skelly, Wanwisa Dejnirattisai, Sandra Adele, Naomi Meardon, Sian Faustini, Saly Al-Taei, Shona C. Moore, Tom Tipton, Luisa M. Hering, Adrienn Angyal, Rebecca Brown, Alexander R. Nicols, Natalie Gillson, Susan L. Dobson, Ali Amini, Piyada Supasa, Andrew Cross, Alice Bridges-Webb, Laura Silva Reyes, Aline Linder, Gurjinder Sandhar, Jonathan A. Kilby, Jessica K. Tyerman, Thomas Altmann, Hailey Hornsby, Rachel Whitham, Eloise Phillips, Tom Malone, Alexander Hargreaves, Adrian Shields, Ayoub Saei, Sarah Foulkes, Lizzie Stafford, Sile Johnson, Daniel G. Wootton, Christopher P. Conlon, Katie Jeffery, Philippa C. Matthews, John Frater, Alexandra S. Deeks, Andrew J. Pollard, Anthony Brown, Sarah L. Rowland-Jones, Juthathip Mongkolsapaya, Eleanor Barnes, Susan Hopkins, Victoria Hall, Christina Dold, Christopher J.A. Duncan, Alex Richter, Miles Carroll, Gavin Screaton, Thushan I. de Silva, Lance Turtle, Paul Klenerman, Susanna Dunachie, Hibatullah Abuelgasim, Emily Adland, Syed Adlou, Hossain Delowar Akther, Ahmed Alhussni, Mohammad Ali, M. Azim Ansari, Carolina V. Arancibia-Cárcamo, Martin Bayley, Helen Brown, Jeremy Chalk, Meera Chand, Anu Chawla, Senthil Chinnakannan, Jospeh Cutteridge, Catherine de Lara, Lucy Denly, Ben Diffey, Stavros Dimitriadis, Thomas M. Drake, Timothy Donnison, Maeva Dupont, David Eyre, Alex Fairman, Siobhan Gardiner, Javier Gilbert-Jarmillo, Philip Goulder, Carl-Philipp Hackstein, Sophie Hambleton, Muzlifah Haniffa, Jenny Haworth, Jennifer Holmes, Emily Horner, Anni Jämsén, Sile Johnson, Chris Jones, Mwila Kasanyinga, Sinead Kelly, Rosemary Kirk, Michael L. Knight, Allan Lawrie, Lian Lee, Lauren Lett, Katy Lillie, Nicholas Lim, Hema Mehta, Alexander J. Mentzer, Denise O’Donnell, Ane Ogbe, Matthew Pace, Brendan A.I. Payne, Gareth Platt, Sonia Poolan, Nicholas Provine, Narayan Ramamurthy, Nichola Robinson, Leigh Romaniuk, Patpong Rongkard, Oliver L. Sampson, Beatrice Simmons, Jarmila S. Spegarova, Emily Stephenson, Kris Subramaniam, James Thaventhiran, Sarah Thomas, Simon Travis, Stephanie Tucker, Helena Turton, Adam Watson, Lisa Watson, Esme Weeks, Robert Wilson, Steven Wood, Rachel Wright, Huiyuan Xiao, Amira A.T. Zawia, Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine, Cell, Volume 184, Issue 23, 2021, Pages 5699-5714.e11, ISSN 0092-8674,

DOI: https://doi.org/10.1016/j.cell.2021.10.011.

Keywords

B cell
BNT162b2
COVID-19
SARS-CoV-2
T cell
antibody
dosing interval
neutralization
vaccine
variants of concern
CELLS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Payne2021ImmunogenicityOfStandardAndExtendedDosingIntervalsOfBNT162b2mRNAVaccineCellFinal published version, 4.92 MBLicence: CC BY

Cite this

@article{d5c708bee91a4398b380c90c7bff2a8a,

title = "Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine",

abstract = "Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.",

keywords = "B cell, BNT162b2, COVID-19, SARS-CoV-2, T cell, antibody, dosing interval, neutralization, vaccine, variants of concern, CELLS",

author = "{PITCH Consortium} and Payne, {Rebecca P.} and Stephanie Longet and Austin, {James A.} and Skelly, {Donal T.} and Wanwisa Dejnirattisai and Sandra Adele and Naomi Meardon and Sian Faustini and Saly Al-Taei and Moore, {Shona C.} and Tom Tipton and Hering, {Luisa M.} and Adrienn Angyal and Rebecca Brown and Nicols, {Alexander R.} and Natalie Gillson and Dobson, {Susan L.} and Ali Amini and Piyada Supasa and Andrew Cross and Alice Bridges-Webb and Reyes, {Laura Silva} and Aline Linder and Gurjinder Sandhar and Kilby, {Jonathan A.} and Tyerman, {Jessica K.} and Thomas Altmann and Hailey Hornsby and Rachel Whitham and Eloise Phillips and Tom Malone and Alexander Hargreaves and Adrian Shields and Ayoub Saei and Sarah Foulkes and Lizzie Stafford and Sile Johnson and Wootton, {Daniel G.} and Conlon, {Christopher P.} and Katie Jeffery and Matthews, {Philippa C.} and John Frater and Deeks, {Alexandra S.} and Pollard, {Andrew J.} and Anthony Brown and Rowland-Jones, {Sarah L.} and Juthathip Mongkolsapaya and Susan Hopkins and Victoria Hall and Miles Carroll",

note = "Funding Information: We are grateful to all our healthcare worker colleagues who participated in the study. For the Birmingham participants, the study was carried out at the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. Laboratory studies were undertaken by the Clinical Immunology Service, University of Birmingham. This work was funded by the United Kingdom Department of Health and Social Care as part of the PITCH 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 COV19-RECPLAS ). A. Amini is funded by a Wellcome clinical research training fellowship ( 216417/Z/19/Z ). E.B. and P.K. are NIHR Senior Investigators, and P.K. is funded by WT109965MA . S.D. is funded by an NIHR global research professorship ( NIHR300791 ). T.I.d.S is funded by a Wellcome Trust intermediate clinical fellowship ( 110058/Z/15/Z ). R.P.P. is funded by a career re-entry fellowship ( 204721/Z/16/Z ). C.J.A.D. is funded by a Wellcome clinical research career development fellowship ( 211153/Z/18/Z ). D.S. is supported by the NIHR Academic Clinical Lecturer Program in Oxford. L.T. is supported by the Wellcome Trust (grant 205228/Z/16/Z ) and the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections ( NIHR200907 ) at the University of Liverpool in partnership with Public Health England (PHE) in collaboration with the Liverpool School of Tropical Medicine and the University of Oxford . D.G.W. is supported by an NIHR advanced fellowship in Liverpool. M.C., A.H., S.L., L.T., and T.T. are supported by US Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085 . The Sheffield Teaching Hospitals Observational Study of Patients with Pulmonary Hypertension, Cardiovascular and other Respiratory Diseases (STH-ObS) was supported by the British Heart Foundation ( PG/11/116/29288 ). The STH-ObS Chief Investigator Allan Laurie is supported by a British Heart Foundation Senior Basic Science Research fellowship ( FS/18/52/33808 ). We gratefully acknowledge financial support from the UK Department of Health via the Sheffield NIHR Clinical Research Facility award to the Sheffield Teaching Hospitals Foundation NHS Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care or Public Health England, or the US Food and Drug Administration. A.J.P. is Chair of the United Kingdom Department of Health and Social Care (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{\textquoteright}s SAGE. The views expressed in this article do not necessarily represent the views of the DHSC, JCVI, or WHO. A.J.P. is chief investigator on clinical trials of Oxford University{\textquoteright}s COVID-19 vaccine funded by NIHR. Oxford University has entered a joint COVID-19 vaccine development partnership with AstraZeneca. Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Elsevier Inc. Citation: Rebecca P. Payne, Stephanie Longet, James A. Austin, Donal T. Skelly, Wanwisa Dejnirattisai, Sandra Adele, Naomi Meardon, Sian Faustini, Saly Al-Taei, Shona C. Moore, Tom Tipton, Luisa M. Hering, Adrienn Angyal, Rebecca Brown, Alexander R. Nicols, Natalie Gillson, Susan L. Dobson, Ali Amini, Piyada Supasa, Andrew Cross, Alice Bridges-Webb, Laura Silva Reyes, Aline Linder, Gurjinder Sandhar, Jonathan A. Kilby, Jessica K. Tyerman, Thomas Altmann, Hailey Hornsby, Rachel Whitham, Eloise Phillips, Tom Malone, Alexander Hargreaves, Adrian Shields, Ayoub Saei, Sarah Foulkes, Lizzie Stafford, Sile Johnson, Daniel G. Wootton, Christopher P. Conlon, Katie Jeffery, Philippa C. Matthews, John Frater, Alexandra S. Deeks, Andrew J. Pollard, Anthony Brown, Sarah L. Rowland-Jones, Juthathip Mongkolsapaya, Eleanor Barnes, Susan Hopkins, Victoria Hall, Christina Dold, Christopher J.A. Duncan, Alex Richter, Miles Carroll, Gavin Screaton, Thushan I. de Silva, Lance Turtle, Paul Klenerman, Susanna Dunachie, Hibatullah Abuelgasim, Emily Adland, Syed Adlou, Hossain Delowar Akther, Ahmed Alhussni, Mohammad Ali, M. Azim Ansari, Carolina V. Arancibia-C{\'a}rcamo, Martin Bayley, Helen Brown, Jeremy Chalk, Meera Chand, Anu Chawla, Senthil Chinnakannan, Jospeh Cutteridge, Catherine de Lara, Lucy Denly, Ben Diffey, Stavros Dimitriadis, Thomas M. Drake, Timothy Donnison, Maeva Dupont, David Eyre, Alex Fairman, Siobhan Gardiner, Javier Gilbert-Jarmillo, Philip Goulder, Carl-Philipp Hackstein, Sophie Hambleton, Muzlifah Haniffa, Jenny Haworth, Jennifer Holmes, Emily Horner, Anni J{\"a}ms{\'e}n, Sile Johnson, Chris Jones, Mwila Kasanyinga, Sinead Kelly, Rosemary Kirk, Michael L. Knight, Allan Lawrie, Lian Lee, Lauren Lett, Katy Lillie, Nicholas Lim, Hema Mehta, Alexander J. Mentzer, Denise O{\textquoteright}Donnell, Ane Ogbe, Matthew Pace, Brendan A.I. Payne, Gareth Platt, Sonia Poolan, Nicholas Provine, Narayan Ramamurthy, Nichola Robinson, Leigh Romaniuk, Patpong Rongkard, Oliver L. Sampson, Beatrice Simmons, Jarmila S. Spegarova, Emily Stephenson, Kris Subramaniam, James Thaventhiran, Sarah Thomas, Simon Travis, Stephanie Tucker, Helena Turton, Adam Watson, Lisa Watson, Esme Weeks, Robert Wilson, Steven Wood, Rachel Wright, Huiyuan Xiao, Amira A.T. Zawia, Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine, Cell, Volume 184, Issue 23, 2021, Pages 5699-5714.e11, ISSN 0092-8674, DOI: https://doi.org/10.1016/j.cell.2021.10.011.",

year = "2021",

month = nov,

day = "11",

doi = "10.1016/j.cell.2021.10.011",

language = "English",

volume = "184",

pages = "5699--5714",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "23",

}

TY - JOUR

T1 - Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

AU - PITCH Consortium

AU - Payne, Rebecca P.

AU - Longet, Stephanie

AU - Austin, James A.

AU - Skelly, Donal T.

AU - Dejnirattisai, Wanwisa

AU - Adele, Sandra

AU - Meardon, Naomi

AU - Faustini, Sian

AU - Al-Taei, Saly

AU - Moore, Shona C.

AU - Tipton, Tom

AU - Hering, Luisa M.

AU - Angyal, Adrienn

AU - Brown, Rebecca

AU - Nicols, Alexander R.

AU - Gillson, Natalie

AU - Dobson, Susan L.

AU - Amini, Ali

AU - Supasa, Piyada

AU - Cross, Andrew

AU - Bridges-Webb, Alice

AU - Reyes, Laura Silva

AU - Linder, Aline

AU - Sandhar, Gurjinder

AU - Kilby, Jonathan A.

AU - Tyerman, Jessica K.

AU - Altmann, Thomas

AU - Hornsby, Hailey

AU - Whitham, Rachel

AU - Phillips, Eloise

AU - Malone, Tom

AU - Hargreaves, Alexander

AU - Shields, Adrian

AU - Saei, Ayoub

AU - Foulkes, Sarah

AU - Stafford, Lizzie

AU - Johnson, Sile

AU - Wootton, Daniel G.

AU - Conlon, Christopher P.

AU - Jeffery, Katie

AU - Matthews, Philippa C.

AU - Frater, John

AU - Deeks, Alexandra S.

AU - Pollard, Andrew J.

AU - Brown, Anthony

AU - Rowland-Jones, Sarah L.

AU - Mongkolsapaya, Juthathip

AU - Hopkins, Susan

AU - Hall, Victoria

AU - Carroll, Miles

N1 - Funding Information: We are grateful to all our healthcare worker colleagues who participated in the study. For the Birmingham participants, the study was carried out at the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. Laboratory studies were undertaken by the Clinical Immunology Service, University of Birmingham. This work was funded by the United Kingdom Department of Health and Social Care as part of the PITCH 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 COV19-RECPLAS ). A. Amini is funded by a Wellcome clinical research training fellowship ( 216417/Z/19/Z ). E.B. and P.K. are NIHR Senior Investigators, and P.K. is funded by WT109965MA . S.D. is funded by an NIHR global research professorship ( NIHR300791 ). T.I.d.S is funded by a Wellcome Trust intermediate clinical fellowship ( 110058/Z/15/Z ). R.P.P. is funded by a career re-entry fellowship ( 204721/Z/16/Z ). C.J.A.D. is funded by a Wellcome clinical research career development fellowship ( 211153/Z/18/Z ). D.S. is supported by the NIHR Academic Clinical Lecturer Program in Oxford. L.T. is supported by the Wellcome Trust (grant 205228/Z/16/Z ) and the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections ( NIHR200907 ) at the University of Liverpool in partnership with Public Health England (PHE) in collaboration with the Liverpool School of Tropical Medicine and the University of Oxford . D.G.W. is supported by an NIHR advanced fellowship in Liverpool. M.C., A.H., S.L., L.T., and T.T. are supported by US Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085 . The Sheffield Teaching Hospitals Observational Study of Patients with Pulmonary Hypertension, Cardiovascular and other Respiratory Diseases (STH-ObS) was supported by the British Heart Foundation ( PG/11/116/29288 ). The STH-ObS Chief Investigator Allan Laurie is supported by a British Heart Foundation Senior Basic Science Research fellowship ( FS/18/52/33808 ). We gratefully acknowledge financial support from the UK Department of Health via the Sheffield NIHR Clinical Research Facility award to the Sheffield Teaching Hospitals Foundation NHS Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care or Public Health England, or the US Food and Drug Administration. A.J.P. is Chair of the United Kingdom Department of Health and Social Care (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 the DHSC, JCVI, or WHO. A.J.P. 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. Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Publisher Copyright: © 2021 The Author(s). Published by Elsevier Inc. Citation: Rebecca P. Payne, Stephanie Longet, James A. Austin, Donal T. Skelly, Wanwisa Dejnirattisai, Sandra Adele, Naomi Meardon, Sian Faustini, Saly Al-Taei, Shona C. Moore, Tom Tipton, Luisa M. Hering, Adrienn Angyal, Rebecca Brown, Alexander R. Nicols, Natalie Gillson, Susan L. Dobson, Ali Amini, Piyada Supasa, Andrew Cross, Alice Bridges-Webb, Laura Silva Reyes, Aline Linder, Gurjinder Sandhar, Jonathan A. Kilby, Jessica K. Tyerman, Thomas Altmann, Hailey Hornsby, Rachel Whitham, Eloise Phillips, Tom Malone, Alexander Hargreaves, Adrian Shields, Ayoub Saei, Sarah Foulkes, Lizzie Stafford, Sile Johnson, Daniel G. Wootton, Christopher P. Conlon, Katie Jeffery, Philippa C. Matthews, John Frater, Alexandra S. Deeks, Andrew J. Pollard, Anthony Brown, Sarah L. Rowland-Jones, Juthathip Mongkolsapaya, Eleanor Barnes, Susan Hopkins, Victoria Hall, Christina Dold, Christopher J.A. Duncan, Alex Richter, Miles Carroll, Gavin Screaton, Thushan I. de Silva, Lance Turtle, Paul Klenerman, Susanna Dunachie, Hibatullah Abuelgasim, Emily Adland, Syed Adlou, Hossain Delowar Akther, Ahmed Alhussni, Mohammad Ali, M. Azim Ansari, Carolina V. Arancibia-Cárcamo, Martin Bayley, Helen Brown, Jeremy Chalk, Meera Chand, Anu Chawla, Senthil Chinnakannan, Jospeh Cutteridge, Catherine de Lara, Lucy Denly, Ben Diffey, Stavros Dimitriadis, Thomas M. Drake, Timothy Donnison, Maeva Dupont, David Eyre, Alex Fairman, Siobhan Gardiner, Javier Gilbert-Jarmillo, Philip Goulder, Carl-Philipp Hackstein, Sophie Hambleton, Muzlifah Haniffa, Jenny Haworth, Jennifer Holmes, Emily Horner, Anni Jämsén, Sile Johnson, Chris Jones, Mwila Kasanyinga, Sinead Kelly, Rosemary Kirk, Michael L. Knight, Allan Lawrie, Lian Lee, Lauren Lett, Katy Lillie, Nicholas Lim, Hema Mehta, Alexander J. Mentzer, Denise O’Donnell, Ane Ogbe, Matthew Pace, Brendan A.I. Payne, Gareth Platt, Sonia Poolan, Nicholas Provine, Narayan Ramamurthy, Nichola Robinson, Leigh Romaniuk, Patpong Rongkard, Oliver L. Sampson, Beatrice Simmons, Jarmila S. Spegarova, Emily Stephenson, Kris Subramaniam, James Thaventhiran, Sarah Thomas, Simon Travis, Stephanie Tucker, Helena Turton, Adam Watson, Lisa Watson, Esme Weeks, Robert Wilson, Steven Wood, Rachel Wright, Huiyuan Xiao, Amira A.T. Zawia, Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine, Cell, Volume 184, Issue 23, 2021, Pages 5699-5714.e11, ISSN 0092-8674, DOI: https://doi.org/10.1016/j.cell.2021.10.011.

PY - 2021/11/11

Y1 - 2021/11/11

N2 - Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.

AB - Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.

KW - B cell

KW - BNT162b2

KW - COVID-19

KW - SARS-CoV-2

KW - T cell

KW - antibody

KW - dosing interval

KW - neutralization

KW - vaccine

KW - variants of concern

KW - CELLS

UR - http://www.scopus.com/inward/record.url?scp=85118834382&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2021.10.011

DO - 10.1016/j.cell.2021.10.011

M3 - Article

AN - SCOPUS:85118834382

SN - 0092-8674

VL - 184

SP - 5699

EP - 5714

JO - Cell

JF - Cell

IS - 23

M1 - e11

ER -

Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Abstract

Bibliographical note

Keywords

UN SDGs

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