Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

PITCH Consortium

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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
Article numbere11
Pages (from-to)5699-5714
Number of pages28
Issue number23
Early online date16 Oct 2021
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.

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 (

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

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


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