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Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections
- Source :
- Repisalud, Instituto de Salud Carlos III (ISCIII), Cell Reports, r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe, instname, Cell Reports, volume 39, issue 1
- Publication Year :
- 2022
- Publisher :
- Cell Press, 2022.
-
Abstract
- Summary MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity.<br />Graphical abstract<br />Highlights • MV130 reduces morbi-mortality in mouse models of viral respiratory infection • MV130 modulates mouse immunity complying with key features of trained immunity • MV130 promotes reprogramming of mouse bone marrow progenitors • MV130 induces trained immunity in human monocytes<br />Brandi et al. investigate the mechanism of action of an inactivated polybacterial mucosal immunomodulator, MV130, which confers protection in patients suffering from recurrent respiratory infections. They show that MV130 induces trained immunity both in mouse bone marrow progenitors, resulting in protection from viral infection, and in human monocytes in vitro.
- Subjects :
- polybacterial immunomodulator
mucosal
human monocytes
Respiratory Mucosa
Antibodies, Viral
Article
General Biochemistry, Genetics and Molecular Biology
Monocytes
Cell Line
trained immunity
Mice
L Cells
Orthomyxoviridae Infections
respiratory infection
Candida albicans
vaccine
Chlorocebus aethiops
Animals
Humans
influenza
Immunity, Mucosal
Lung
Respiratory Tract Infections
viral infection
Administration, Intranasal
Mice, Knockout
Bacteria
Candidiasis
Metformin
macrophages
Mice, Inbred C57BL
Vaccines, Inactivated
Influenza A virus
Bacterial Vaccines
Cytokines
Subjects
Details
- ISSN :
- 22111247
- Database :
- OpenAIRE
- Journal :
- Repisalud, Instituto de Salud Carlos III (ISCIII), Cell Reports, r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe, instname, Cell Reports, volume 39, issue 1
- Accession number :
- edsair.doi.dedup.....6655ea6db963d630136bc10e9a6c7b72