No evidence of durable trained immunity after two doses of adenovirus-vectored or mRNA COVID-19 vaccines

Natalie E. Stevens, Feargal J. Ryan, Nicole L. Messina, Stephen J. Blake, Todd S. Norton, Susie Germano, Jane James, Georgina L. Eden, Yee C. Tee, Miriam A. Lynn, Rochelle Botten, Simone E. Barry, Nigel Curtis, David J. Lynn

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To the Editor: Trained immunity (TI) is defined as the long-term metabolic and epigenomic reprogramming of innate immune cells, priming them for enhanced responses to subsequent challenges, including unrelated infections. Recently, Murphy et al.
reported in the JCI that three months after one dose of the ChAdOx1-S (Oxford/AstraZeneca) adenovirus-vectored SARS-CoV-2 vaccine, multiple changes consistent with TI were observed in a cohort of 10 individuals. These changes included an increased frequency of circulating monocytes, enhanced monocyte activation marker expression, and increased cytokine and chemokine responses. Whether these changes were accompanied by epigenomic reprogramming of monocytes, a hallmark of TI, was not assessed. In contrast, Yamaguchi et al. reported only transient epigenomic and transcriptomic changes in monocytes collected from five individuals following two doses of the BNT162b2 (Pfizer/BioNTech) mRNA vaccine. These findings suggest that ChAdOx1-S but not BNT162b2 vaccination induces TI, which could have important implications for the use of COVID-19 vaccines globally...
Original languageEnglish
Article numbere171742
Number of pages2
JournalJournal of Clinical Investigation
Issue number17
Early online date20 Jul 2023
Publication statusPublished - 1 Sept 2023


  • COVID-19
  • Epigenetics
  • Innate immunity
  • Monocytes
  • Vaccines


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