Reference Database

Stronger induction of trained immunity by mucosal BCG or MTBVAC vaccination compared to standard intradermal vaccination.
Vierboom, Michel P M
Dijkman, Karin
Sombroek, Claudia C
Hofman, Sam O
Boot, Charelle
Vervenne, Richard A W
Haanstra, Krista G
van der Sande, Maarten
van Emst, Liesbeth
Domínguez-Andrés, Jorge
Moorlag, Simone J C F M
Kocken, Clemens H M
Thole, Jelle
Rodríguez, Esteban
Puentes, Eugenia
Martens, Joost H A
van Crevel, Reinout
Netea, Mihai G
Aguilo, Nacho
Martin, Carlos
Verreck, Frank A W
Cell reports. Medicine 2021 Jan 19;2: 100185

BCG vaccination can strengthen protection against pathogens through the induction of epigenetic and metabolic reprogramming of innate immune cells, a process called trained immunity. We and others recently demonstrated that mucosal or intravenous BCG better protects rhesus macaques from infection and TB disease than standard intradermal vaccination, correlating with local adaptive immune signatures. In line with prior mouse data, here, we show in rhesus macaques that intravenous BCG enhances innate cytokine production associated with changes in H3K27 acetylation typical of trained immunity. Alternative delivery of BCG does not alter the cytokine production of unfractionated bronchial lavage cells. However, mucosal but not intradermal vaccination, either with BCG or the -derived candidate MTBVAC, enhances innate cytokine production by blood- and bone marrow-derived monocytes associated with metabolic rewiring, typical of trained immunity. These results provide support to strategies for improving TB vaccination and, more broadly, modulating innate immunity via mucosal surfaces.

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