Pre-existing immunity modulates responses to mRNA boosters

Tanushree Dangi, Sarah Sanchez, Min Han Lew, Bakare Awakoaiye, Lavanya Visvabharathy, Justin M. Richner, Igor J. Koralnik, Pablo Penaloza-MacMaster*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


mRNA vaccines are effective in preventing severe COVID-19, but breakthrough infections, emerging variants, and waning immunity warrant the use of boosters. Although mRNA boosters are being implemented, the extent to which pre-existing immunity influences the efficacy of boosters remains unclear. In a cohort of individuals primed with the mRNA-1273 or BNT162b2 vaccines, we report that lower antibody levels before boost are associated with higher fold-increase in antibody levels after boost, suggesting that pre-existing antibody modulates the immunogenicity of mRNA vaccines. Our studies in mice show that pre-existing antibodies accelerate the clearance of vaccine antigen via Fc-dependent mechanisms, limiting the amount of antigen available to prime B cell responses after mRNA boosters. These data demonstrate a “tug of war” between pre-existing antibody responses and de novo B cell responses following mRNA vaccination, and they suggest that transient downmodulation of antibody effector function may improve the efficacy of mRNA boosters.

Original languageEnglish (US)
Article number112167
JournalCell reports
Issue number3
StatePublished - Mar 28 2023


  • antibody effector functions
  • CP: Immunology
  • mRNA vaccines
  • Omicron variant
  • pre-existing immunity
  • SARS-CoV-2
  • updated vaccines

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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