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Stronger induction of trained immunity by mucosal BCG or MTBVAC vaccination compared to standard intradermal vaccination
- Source :
- Cell Reports Medicine, 2, 1, Zaguán: Repositorio Digital de la Universidad de Zaragoza, Universidad de Zaragoza, Zaguán. Repositorio Digital de la Universidad de Zaragoza, instname, Cell Rep Med., Cell Reports Medicine, Cell Reports Medicine, 2
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- 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.<br />Graphical Abstract<br />Highlights Nonhuman primates recapitulate trained immunity upon live attenuated TB vaccination Intravenous BCG induces changes in H3K27 acetylation and enhances cytokine production Mucosal BCG improves induction of trained immunity of monocytes over intradermal BCG The M. tuberculosis-derived candidate vaccine MTBVAC appears equally potent as BCG<br />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.
- Subjects :
- Male
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
medicine.medical_treatment
Interleukin-1beta
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
Monocytes
Histones
trained immunity
0302 clinical medicine
Bone Marrow
BCG
030212 general & internal medicine
Tuberculosis Vaccines
innate immunity
Lung
0303 health sciences
biology
Acetylation
Cellular Reprogramming
3. Good health
Vaccination
Cytokine
tuberculosis
Injections, Intravenous
BCG Vaccine
Female
immunotherapy
non-human primates
Molecular Developmental Biology
Tuberculosis
Respiratory Mucosa
Article
General Biochemistry, Genetics and Molecular Biology
Mycobacterium tuberculosis
03 medical and health sciences
Immune system
Immunity
medicine
Animals
MTBVAC
Immunity, Mucosal
Tuberculosis, Pulmonary
Molecular Biology
Administration, Intranasal
030304 developmental biology
Innate immune system
Interleukin-6
Tumor Necrosis Factor-alpha
business.industry
Immunotherapy
biochemical phenomena, metabolism, and nutrition
vaccination
biology.organism_classification
medicine.disease
Macaca mulatta
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4]
vaccine development
Gene Expression Regulation
Immunology
business
Subjects
Details
- ISSN :
- 26663791
- Volume :
- 2
- Database :
- OpenAIRE
- Journal :
- Cell Reports Medicine
- Accession number :
- edsair.doi.dedup.....6ce3e7265c370cb7846bfb2713fcc852