Imprinted SARS-CoV-2-specific memory lymphocytes define hybrid immunity

Cell. 2022 Apr 28;185(9):1588-1601.e14. doi: 10.1016/j.cell.2022.03.018. Epub 2022 Mar 17.


Immune memory is tailored by cues that lymphocytes perceive during priming. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic created a situation in which nascent memory could be tracked through additional antigen exposures. Both SARS-CoV-2 infection and vaccination induce multifaceted, functional immune memory, but together, they engender improved protection from disease, termed hybrid immunity. We therefore investigated how vaccine-induced memory is shaped by previous infection. We found that following vaccination, previously infected individuals generated more SARS-CoV-2 RBD-specific memory B cells and variant-neutralizing antibodies and a distinct population of IFN-γ and IL-10-expressing memory SARS-CoV-2 spike-specific CD4+ T cells than previously naive individuals. Although additional vaccination could increase humoral memory in previously naive individuals, it did not recapitulate the distinct CD4+ T cell cytokine profile observed in previously infected subjects. Thus, imprinted features of SARS-CoV-2-specific memory lymphocytes define hybrid immunity.

Keywords: COVID-19; SARS-CoV-2; adaptive immune response; human; hybrid Immunity; memory B cell; memory T cell; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines / immunology*
  • COVID-19* / immunology
  • Humans
  • Immunity, Humoral
  • SARS-CoV-2*
  • Spike Glycoprotein, Coronavirus
  • T-Lymphocytes


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2