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

Lauren B. Rodda, Peter A. Morawski, Kurt B. Pruner, Mitchell L. Fahning, Christian A. Howard, Nicholas Franko, Jennifer Logue, Julie Eggenberger, Caleb Stokes, Inah Golez, Malika Hale, Michael Gale, Helen Y. Chu, Daniel J. Campbell, Marion Pepper

Research output: Contribution to journalArticlepeer-review

114 Scopus citations


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.

Original languageEnglish
Pages (from-to)1588-1601.e14
Issue number9
StatePublished - 28 Apr 2022
Externally publishedYes


  • COVID-19
  • SARS-CoV-2
  • adaptive immune response
  • human
  • hybrid Immunity
  • memory B cell
  • memory T cell
  • vaccine


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