Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections

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 i...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2022-01, Vol.38 (1), p.110184-110184, Article 110184
Main Authors: Brandi, Paola, Conejero, Laura, Cueto, Francisco J, Martínez-Cano, Sarai, Dunphy, Gillian, Gómez, Manuel J, Relaño, Carlos, Saz-Leal, Paula, Enamorado, Michel, Quintas, Ana, Dopazo, Ana, Amores-Iniesta, Joaquín, Del Fresno, Carlos, Nistal-Villán, Estanislao, Ardavín, Carlos, Nieto, Antonio, Casanovas, Miguel, Subiza, José Luis, Sancho, David
Format: Article
Language:English
Subjects:
Administration, Intranasal
Animals
Antibodies, Viral - immunology
Bacteria - immunology
Bacterial Vaccines - administration & dosage
Bacterial Vaccines - immunology
Candidiasis - prevention & control
Cell Line
Chlorocebus aethiops
Cytokines - biosynthesis
Humans
Immunity, Mucosal - immunology
Influenza A virus - immunology
L Cells
Lung - immunology
Metformin - pharmacology
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocytes - immunology
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - prevention & control
Orthomyxoviridae Infections - virology
Respiratory Mucosa - immunology
Respiratory Tract Infections - microbiology
Respiratory Tract Infections - prevention & control
Respiratory Tract Infections - virology
Vaccines, Inactivated - administration & dosage
Vaccines, Inactivated - immunology
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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.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2021.110184