Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Cell. 2021 Nov 11;184(23):5699-5714.e11. doi: 10.1016/j.cell.2021.10.011. Epub 2021 Oct 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • BNT162 Vaccine
  • COVID-19 / blood
  • COVID-19 / immunology
  • COVID-19 / virology
  • COVID-19 Vaccines / immunology*
  • Cross-Priming / immunology
  • Dose-Response Relationship, Immunologic
  • Ethnicity
  • Female
  • Humans
  • Immunity
  • Immunoglobulin G / immunology
  • Linear Models
  • Male
  • Middle Aged
  • Reference Standards
  • SARS-CoV-2 / immunology
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Vaccines, Synthetic / immunology*
  • Young Adult
  • mRNA Vaccines


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immunoglobulin G
  • Vaccines, Synthetic
  • BNT162 Vaccine