Neonatal BCG Vaccination is Associated with a Long-term DNA Methylation Signature in Circulating Monocytes

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2022 Aug 5

PMID 35930640

Authors

Samantha Bannister

Bowon Kim

Jorge Dominguez-Andres

Gizem Kilic

Brendan R E Ansell

Melanie R Neeland

Simone J C F M Moorlag

Vasiliki Matzaraki

Amanda Vlahos

Rebecca Shepherd

Susie Germano

Melanie Bahlo

Nicole L Messina

Richard Saffery

Mihai G Netea

Nigel Curtis

Boris Novakovic

Affiliations

Soon will be listed here.

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.

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