The impact of BCG dose and revaccination on trained immunity

Priya A. Debisarun, Gizem Kilic, L. Charlotte J. de Bree, Lian J. Pennings, Jakko van Ingen, Christine S. Benn, Peter Aaby, Helga Dijkstra, Heidi Lemmers, Jorge Domínguez-Andrés, Reinout van Crevel, Mihai G. Netea*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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The innate immune system can display heterologous memory-like responses termed trained immunity after stimulation by certain vaccinations or infections. In this randomized, placebo-controlled trial, we investigated the modulation of Bacille Calmette-Guérin (BCG)-induced trained immunity by BCG revaccination or high-dose BCG administration, in comparison to a standard dose. We show that monocytes from all groups of BCG-vaccinated individuals exerted increased TNFα production after ex-vivo stimulation with various unrelated pathogens. Similarly, we observed increased amounts of T-cell-derived IFNγ after M. tuberculosis exposure, regardless of the BCG intervention. NK cell cytokine production, especially after heterologous stimulation with the fungal pathogen Candida albicans, was predominantly boosted after high dose BCG administration. Cytokine production capacity before vaccination was inversely correlated with trained immunity. While the induction of a trained immunity profile is largely dose- or frequency independent, baseline cytokine production capacity is associated with the magnitude of the innate immune memory response after BCG vaccination.

Original languageEnglish
Article number109208
JournalClinical Immunology
Number of pages7
Publication statusPublished - Jan 2023

Bibliographical note

Publisher Copyright:
© 2022 The Authors


  • Bacille Calmette-Guérin
  • Booster
  • Innate immune memory
  • Mycobacterium tuberculosis
  • Non-specific beneficial effects
  • Revaccination


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