Stronger induction of trained immunity by mucosal BCG or MTBVAC vaccination compared to standard intradermal vaccination.
Michel P M Vierboom, Karin Dijkman, Claudia C Sombroek, Sam O Hofman, Charelle Boot, Richard A W Vervenne, Krista G Haanstra, Maarten van der Sande, Liesbeth van Emst, Jorge Domínguez-Andrés, Simone J C F M Moorlag, Clemens H M Kocken, Jelle Thole, Esteban Rodríguez, Eugenia Puentes, Joost H A Martens, Reinout van Crevel, Mihai G Netea, Nacho Aguilo, Carlos Martin, Frank A W Verreck
Author Information
Michel P M Vierboom: Biomedical Primate Research Centre, Rijswijk, the Netherlands.
Karin Dijkman: Biomedical Primate Research Centre, Rijswijk, the Netherlands.
Claudia C Sombroek: Biomedical Primate Research Centre, Rijswijk, the Netherlands.
Sam O Hofman: Biomedical Primate Research Centre, Rijswijk, the Netherlands.
Charelle Boot: Biomedical Primate Research Centre, Rijswijk, the Netherlands.
Richard A W Vervenne: Biomedical Primate Research Centre, Rijswijk, the Netherlands.
Krista G Haanstra: Biomedical Primate Research Centre, Rijswijk, the Netherlands.
Maarten van der Sande: Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, the Netherlands.
Liesbeth van Emst: Radboud University Medical Centre, Nijmegen, the Netherlands.
Jorge Domínguez-Andrés: Radboud University Medical Centre, Nijmegen, the Netherlands.
Simone J C F M Moorlag: Radboud University Medical Centre, Nijmegen, the Netherlands.
Clemens H M Kocken: Biomedical Primate Research Centre, Rijswijk, the Netherlands.
Jelle Thole: TuBerculosis Vaccine Initiative, Lelystad, the Netherlands.
Esteban Rodríguez: Biofabri, Pontevedra, Spain.
Eugenia Puentes: Biofabri, Pontevedra, Spain.
Joost H A Martens: Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, the Netherlands.
Reinout van Crevel: Radboud University Medical Centre, Nijmegen, the Netherlands.
Mihai G Netea: Radboud University Medical Centre, Nijmegen, the Netherlands.
Nacho Aguilo: Department of Microbiology, Faculty of Medicine, IIS Aragón, University of Zaragoza, Zaragoza, Spain.
Carlos Martin: Department of Microbiology, Faculty of Medicine, IIS Aragón, University of Zaragoza, Zaragoza, Spain.
Frank A W Verreck: Biomedical Primate Research Centre, Rijswijk, the Netherlands.
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.
