Cellular and humoral functional responses after BNT162b2 mRNA vaccination differ longitudinally between naive and subjects recovered from COVID-19

Cell Rep. 2022 Jan 11;38(2):110235. doi: 10.1016/j.celrep.2021.110235. Epub 2021 Dec 21.


We have analyzed BNT162b2 vaccine-induced immune responses in naive subjects and individuals recovered from coronavirus disease 2019 (COVID-19), both soon after (14 days) and later after (almost 8 months) vaccination. Plasma spike (S)-specific immunoglobulins peak after one vaccine shot in individuals recovered from COVID-19, while a second dose is needed in naive subjects, although the latter group shows reduced levels all along the analyzed period. Despite how the neutralization capacity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mirrors this behavior early after vaccination, both groups show comparable neutralizing antibodies and S-specific B cell levels late post-vaccination. When studying cellular responses, naive individuals exhibit higher SARS-CoV-2-specific cytokine production, CD4+ T cell activation, and proliferation than do individuals recovered from COVID-19, with patent inverse correlations between humoral and cellular variables early post-vaccination. However, almost 8 months post-vaccination, SARS-CoV-2-specific responses are comparable between both groups. Our data indicate that a previous history of COVID-19 differentially determines the functional T and B cell-mediated responses to BNT162b2 vaccination over time.

Keywords: BNT162b2 vaccine; COVID-19-recovered; SARS-CoV-2; antigen-specific T cell; cellular responses; cytokine production; humoral responses; memory B cell; proliferation; spike.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology
  • BNT162 Vaccine / immunology*
  • COVID-19 / immunology*
  • COVID-19 / virology
  • COVID-19 Vaccines / immunology*
  • Chlorocebus aethiops
  • Humans
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / immunology*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology
  • Lymphocyte Activation / immunology
  • SARS-CoV-2 / immunology
  • Spike Glycoprotein, Coronavirus / immunology
  • Vaccination / methods
  • Vaccines, Synthetic / immunology*
  • Vero Cells
  • mRNA Vaccines / immunology*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Synthetic
  • mRNA Vaccines
  • BNT162 Vaccine