Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

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 CrossAlice 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, 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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 languageEnglish
Pages (from-to)5699-5714.e11
JournalCell
Volume184
Issue number23
DOIs
Publication statusPublished - 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 .

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. Conceptualization, S.D. P.K. R.P.P. L.T. T.I.d.S. S.H. V.H. C.J.A.D. A.R. M.C. and G. Screaton; methodology, S.D. P.K. R.P.P. L.T. T.I.d.S. C.J.A.D. A.R. M.C. G. Screaton, C.D. N.G. S.H. and V.H.; formal analysis, R.P.P. S.D. L.T. T.I.d.S. C.D. S.L. J.A.A. D.T.S. W.D. A. Saei, S. Foulkes, and A.S.D. investigation, R.P.P. S.L. J.A.A. D.T.S. W.D. S.A. N.M. S. Faustini, S.A.-T. S.C.M. T.T. L.M.H. A. Angyal, R.B. A.R.N. S.L.D. A. Amini, P.S. A.C. A.B.-W. L.S.R. A.L. G. Sandhar, J.A.K. J.K.T. T.A. H.H. R.W. E.P. T.M. A.H. A. Shields, A. Saei, S. Foulkes, L.S. S.J. D.G.W. and A.B.; resources, A.B. L.T. and E.B.; data curation, R.P.P. and A.D.; writing ? original draft, R.P.P. S.D. P.K. L.T. and T.I.d.S. writing ? review & editing, S.L. J.A.A. S.L.D. S.J. D.G.W. C.P.C. K.J. P.C.M. A.J.P. J.M. E.B. A.R. M.C. and G. Screaton; visualization, R.P.P. S.L. J.A.A. D.T.S. A.R.N. A. Shields, A. Saei, S. Foulkes, L.T. and S.D. supervision, R.P.P. C.P.C. K.J. J.F. A.J.P. S.L.R-J. J.M. E.B. S.H. V.H. C.D. C.J.A.D. A.R. M.C. G. Screaton, T.I.d.S. L.T. P.K. and S.D. project administration, A.S.D. and N.G. funding acquisition, P.K. S.D. L.T. T.I.d.S. C.J.A.D. and A.R. 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.

Publisher Copyright:
© 2021 The Author(s)

Keywords

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

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