Cell
Volume 184, Issue 23, 11 November 2021, Pages 5699-5714.e11
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Article
Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

https://doi.org/10.1016/j.cell.2021.10.011Get rights and content
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Highlights

  • BNT162b2 vaccine with an extended interval between doses is highly protective

  • Antibody levels were higher after the extended regimen compared with the short regimen

  • The extended regimen enriches for virus-specific CD4+ T cells expressing IL-2

  • Antibody levels wane after each dose, but B and T cell pools are maintained

Summary

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

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

Data and code availability

  • IFN ELISpot data, MSD data, ACE2 inhibition data, neutralizing antibody data and intracellular cytokine assay data derived from human samples have been deposited at Mendeley Data and are publicly available as of the date of publication. The DOI is listed in the key resources table.

  • De-identified participant metadata have been deposited with the above Mendeley data and are publicly available as of the date of publication.

  • This paper does not report original code.

  • Any additional information required to reanalyse the data reported in this paper is available from the lead contact upon request.

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