Stronger induction of trained immunity by mucosal BCG or MTBVAC vaccination compared to standard intradermal vaccination

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 Mycobacteriu...

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Published in:Cell reports. Medicine 2021-01, Vol.2 (1), p.100185-100185, Article 100185
Main Authors: 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.
Format: Article
Language:English
Subjects:
Acetylation
Administration, Intranasal
Animals
BCG
BCG Vaccine - administration & dosage
Bone Marrow - drug effects
Bone Marrow - immunology
Bone Marrow - microbiology
Cellular Reprogramming - genetics
Cellular Reprogramming - immunology
Female
Gene Expression Regulation
Histones - genetics
Histones - immunology
Immunity, Mucosal
immunotherapy
Injections, Intravenous
innate immunity
Interleukin-1beta - genetics
Interleukin-1beta - immunology
Interleukin-6 - genetics
Interleukin-6 - immunology
Lung - drug effects
Lung - immunology
Lung - microbiology
Macaca mulatta
Male
Monocytes - drug effects
Monocytes - immunology
Monocytes - microbiology
MTBVAC
Mycobacterium tuberculosis - immunology
Mycobacterium tuberculosis - pathogenicity
non-human primates
Respiratory Mucosa - immunology
Respiratory Mucosa - microbiology
trained immunity
tuberculosis
Tuberculosis Vaccines - administration & dosage
Tuberculosis, Pulmonary - genetics
Tuberculosis, Pulmonary - immunology
Tuberculosis, Pulmonary - microbiology
Tuberculosis, Pulmonary - prevention & control
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - immunology
vaccination
vaccine development
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Summary: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 Mycobacterium tuberculosis 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 M. tuberculosis-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. [Display omitted] Nonhuman primates recapitulate trained immunity upon live attenuated TB vaccinationIntravenous BCG induces changes in H3K27 acetylation and enhances cytokine productionMucosal BCG improves induction of trained immunity of monocytes over intradermal BCGThe M. tuberculosis-derived candidate vaccine MTBVAC appears equally potent as BCG Vierboom et al. demonstrate the induction of trained immunity in blood and bone marrow monocytes after vaccination with live attenuated TB vaccines in nonhuman primates. Mucosal respiratory delivery of BCG or MTBVAC induces trained immunity more efficiently compared to standard intradermal vaccination.
ISSN:2666-3791
2666-3791
DOI:10.1016/j.xcrm.2020.100185