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

• DOI: 10.1016/j.celrep.2021.110184
• Publication Date: 2022-01-04T15:45:19Z
• Authors: Paola Brandi; Laura Conejero; Francisco J. Cueto; Sarai Martínez-Cano; Gillian Dunphy; Manuel J. Gómez; Carlos Relaño; Paula Saz-Leal; Michel Enamorado; Ana Quintas; Ana Dopazo; Joaquín Amores-In...; Carlos del Fresno; Estanislao Nistal...; Carlos Ardavín; Antonio Nieto; Miguel Casanovas; José Luis Subiza; David Sancho
• Keywords: *polybacterial immunomodulator; Respiratory Mucosa; Trained immunity; Antibodies, Viral; Article; Monocytes; *human monocytes; Cell Line; *mucosal; *trained immunity; Mice; 03 medical and health sciences; L Cells; Orthomyxoviridae Infections; Respiratory infection; *Candida albicans; Candida albicans; Chlorocebus aethiops; Animals; Humans; Polybacterial immunomodulator; *influenza; Respiratory Tract Infections; Immunity, Mucosal; Lung; *viral infection; Administration, Intranasal; Mice, Knockout; Mucosal; 0303 health sciences; Bacteria; Macrophages; Candidiasis; Influenza; Metformin; 3. Good health; Mice, Inbred C57BL; Vaccines, Inactivated; Viral infection; Influenza A virus; Human monocytes; *macrophages; Bacterial Vaccines; Cytokines; Vaccine; *respiratory infection; *vaccine

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.