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Neonatal BCG vaccination is associated with a long-term DNA methylation signature in circulating monocytes.

Authors :
Bannister S
Kim B
Domínguez-Andrés J
Kilic G
Ansell BRE
Neeland MR
Moorlag SJCFM
Matzaraki V
Vlahos A
Shepherd R
Germano S
Bahlo M
Messina NL
Saffery R
Netea MG
Curtis N
Novakovic B
Source :
Science advances [Sci Adv] 2022 Aug 05; Vol. 8 (31), pp. eabn4002. Date of Electronic Publication: 2022 Aug 05.
Publication Year :
2022

Abstract

Trained immunity describes the capacity of innate immune cells to develop heterologous memory in response to certain exogenous exposures. This phenomenon mediates, at least in part, the beneficial off-target effects of the BCG vaccine. Using an in vitro model of trained immunity, we show that BCG exposure induces a persistent change in active histone modifications, DNA methylation, transcription, and adenosine-to-inosine RNA modification in human monocytes. By profiling DNA methylation of circulating monocytes from infants in the MIS BAIR clinical trial, we identify a BCG-associated DNA methylation signature that persisted more than 12 months after neonatal BCG vaccination. Genes associated with this epigenetic signature are involved in viral response pathways, consistent with the reported off-target protection against viral infections in neonates, adults, and the elderly. Our findings indicate that the off-target effects of BCG in infants are accompanied by epigenetic remodeling of circulating monocytes that lasts more than 1 year.

Details

Language :
English
ISSN :
2375-2548
Volume :
8
Issue :
31
Database :
MEDLINE
Journal :
Science advances
Publication Type :
Academic Journal
Accession number :
35930640
Full Text :
https://doi.org/10.1126/sciadv.abn4002