Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine
Open accessAbstract
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.
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A growing number of studies suggest that an extended dosing interval amplifies both the humoral immune response and perhaps the cellular response, and is an effective global strategy given discrepancies between regions with high and low vaccination coverage.
“Nonetheless, a growing number of studies suggest that an extended dosing interval amplifies both the humoral immune response30 and perhaps the cellular response,31 and is an effective global strategy given the discrepancies between regions with high and low vaccination coverage.32”
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- Authors
- Payne, R. P., Longet, S., Austin, J. A., Skelly, D. T., Dejnirattisai, W., Adele, S., Meardon, N., Faustini, S., Al-Taei, S., Moore, S. C., Tipton, T., Hering, L. M., Angyal, A., Brown, R., Nicols, A. R., Gillson, N., Dobson, S. L., Amini, A., Supasa, P., Cross, A., Bridges-Webb, A., Reyes, L. S., Linder, A., Sandhar, G., Kilby, J. A., Tyerman, J. K., Altmann, T., Hornsby, H., Whitham, R., Phillips, E., Malone, T., Hargreaves, A., Shields, A., Saei, A., Foulkes, S., Stafford, L., Johnson, S., Wootton, D. G., Conlon, C. P., Jeffery, K., Matthews, P. C., Frater, J., Deeks, A. S., Pollard, A. J., Brown, A., Rowland-Jones, S. L., Mongkolsapaya, J., Barnes, E., Hopkins, S., Hall, V., Dold, C., Duncan, C. J. A., Richter, A., Carroll, M., Screaton, G., de Silva, T. I., Turtle, L., Klenerman, P., Dunachie, S., Abuelgasim, H., Adland, E., Adlou, S., Akther, H. D., Alhussni, A., Ali, M., Ansari, M. A., Arancibia-Cárcamo, C. V., Bayley, M., Brown, H., Chalk, J., Chand, M., Chawla, A., Chinnakannan, S., Cutteridge, J., de Lara, C., Denly, L., Diffey, B., Dimitriadis, S., Drake, T. M., Donnison, T., Dupont, M., Eyre, D., Fairman, A., Gardiner, S., Gilbert-Jarmillo, J., Goulder, P., Hackstein, C.-P., Hambleton, S., Haniffa, M., Haworth, J., Holmes, J., Horner, E., Jämsén, A., Johnson, S., Jones, C., Kasanyinga, M., Kelly, S., Kirk, R., Knight, M. L., Lawrie, A., Lee, L., Lett, L., Lillie, K., Lim, N., Mehta, H., Mentzer, A. J., O’Donnell, D., Ogbe, A., Pace, M., Payne, B. A. I., Platt, G., Poolan, S., Provine, N., Ramamurthy, N., Robinson, N., Romaniuk, L., Rongkard, P., Sampson, O. L., Simmons, B., Spegarova, J. S., Stephenson, E., Subramaniam, K., Thaventhiran, J., Thomas, S., Travis, S., Tucker, S., Turton, H., Watson, A., Watson, L., Weeks, E., Wilson, R., Wood, S., Wright, R., Xiao, H., & Zawia, A. A. T.
- Affiliations
- Newcastle University (GB)
- University of Liverpool (GB)
- University of Oxford (GB)
- Centre for Human Genetics (GB)
- Sheffield Teaching Hospitals NHS Foundation Trust (GB)
- University of Birmingham (GB)
- University of Sheffield (GB)
- Public Health England (GB)
- Liverpool University Hospitals NHS Foundation Trust (GB)
- Great North Children's Hospital (GB)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Oxford University Hospitals NHS Trust (GB)
- Siriraj Hospital (TH)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- Corresponding author
- Payne, Rebecca P.
- Klenerman, Paul
- ORCID
- Payne, Rebecca P.
- Austin, James A.
- Skelly, Donal T.
- Dejnirattisai, Wanwisa
- Adele, Sandra
- Faustini, Sian
- Moore, Shona C.
- Tipton, Tom
- Hering, Luisa M.
- Angyal, Adrienn
- Brown, Rebecca
- Nicols, Alexander R.
- Gillson, Natalie
- Dobson, Susan L.
- Amini, Ali
- Supasa, Piyada
- Reyes, Laura Silva
- Linder, Aline
- Tyerman, Jessica K.
- Altmann, Thomas
- Hornsby, Hailey
- Phillips, Eloise
- Hargreaves, Alexander
- Shields, Adrian
- Saei, Ayoub
- Foulkes, Sarah
- Stafford, Lizzie
- Conlon, Christopher P.
- Jeffery, Katie
- Matthews, Philippa C.
- Frater, John
- Deeks, Alexandra S.
- Pollard, Andrew J.
- Brown, Anthony
- Mongkolsapaya, Juthathip
- Barnes, Eleanor
- Hopkins, Susan
- Hall, Victoria
- Dold, Christina
- Duncan, Christopher J.A.
- Richter, Alex
- Carroll, Miles
- Screaton, Gavin
- Turtle, Lance
- Klenerman, Paul
- Dunachie, Susanna
- Abuelgasim, Hibatullah
- Alhussni, Ahmed
- Ali, Mohammad
- Ansari, M. Azim
- Arancibia-Cárcamo, Carolina V.
- Chalk, Jeremy
- Chand, Meera
- Chinnakannan, Senthil
- Cutteridge, Joseph
- Denly, Lucy
- Dimitriadis, Stavros
- Drake, Thomas M.
- Donnison, Timothy
- Dupont, Maeva
- Eyre, David
- Gardiner, Siobhan
- Goulder, Philip
- Hackstein, Carl-Philipp
- Hambleton, Sophie
- Haniffa, Muzlifah
- Holmes, Jennifer
- Horner, Emily
- Kasanyinga, Mwila
- Knight, Michael L.
- Lawrie, Allan
- Lee, Lian
- Lett, Lauren
- Lillie, Katy
- Lim, Nicholas
- Mentzer, Alexander J.
- Ogbe, Ane
- Pace, Matthew
- Payne, Brendan A.I.
- Platt, Gareth
- Provine, Nicholas
- Ramamurthy, Narayan
- Rongkard, Patpong
- Sampson, Oliver L.
- Spegarova, Jarmila S.
- Stephenson, Emily
- Thaventhiran, James
- Thomas, Sarah
- Travis, Simon
- Turton, Helena
- Watson, Adam
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 184
- Issue
- 23
- Pages
- 5699-5714.e11
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8519781
- OpenAlex
- W3206717788
- Cited by
- 322
- References
- 47
- Citations by year
- 2026: 14 · 2025: 33 · 2024: 34 · 2023: 87 · 2022: 135 · 2021: 18
- FWCI
- 21.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Greater South Information System
- Funders
- University of Liverpool
- Oxford University
- UK Research and Innovation
- Wellcome Trust (NIHR300791, 216417/Z/19/Z, 204721/Z/16/Z, 110058/Z/15/Z)
- U.S. Food and Drug Administration
- National Institute for Health Research
- Utah Department of Health
- Sheffield Teaching Hospitals NHS Foundation Trust
- Department of Health and Social Care
- University of Birmingham
- British Heart Foundation (FS/18/52/33808, PG/11/116/29288)
- Public Health England
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Keywords
- BNT162b2 mRNA vaccine, extended dosing interval, single-dose vaccination, immunogenicity, neutralizing antibodies, spike protein, CD4+ T cells, interleukin-2, SARS-CoV-2, prior SARS-CoV-2 infection, healthcare workers
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, BNT162 Vaccine, Adult, Aged, Antibodies, Viral, Dose-Response Relationship, Immunologic, Ethnicity, Female, Humans, Immunoglobulin G, Immunity, Male, Middle Aged, Reference Standards, T-Lymphocytes, Vaccines, Synthetic, Linear Models, Treatment Outcome, Cross-Priming, Young Adult, Antibodies, Neutralizing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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