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

Autor:	Brandi P; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Conejero L; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Cueto FJ; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Martínez-Cano S; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Inmunotek S.L., Alcalá de Henares, Spain., Dunphy G; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Gómez MJ; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Relaño C; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Saz-Leal P; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Enamorado M; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Quintas A; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Dopazo A; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Amores-Iniesta J; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Del Fresno C; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Instituto de Investigación Biomédica del Hospital Universitario La Paz (IdiPAZ), Madrid, Spain., Nistal-Villán E; Microbiology Section, Department Pharmacological and Health Sciences, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain., Ardavín C; Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Madrid, Spain., Nieto A; Pediatric Pulmonology & Allergy Unit, Health Research Institute, La Fe University Hospital, Valencia, Spain., Casanovas M; Inmunotek S.L., Alcalá de Henares, Spain., Subiza JL; Inmunotek S.L., Alcalá de Henares, Spain., Sancho D; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Electronic address: dsancho@cnic.es.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Jan 04; Vol. 38 (1), pp. 110184.
DOI:	10.1016/j.celrep.2021.110184
Abstrakt:	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. Competing Interests: Declaration of interests J.L.S., M.C., L.C., S. M.-C., and P.S.-L. were employees of Inmunotek S.L. at the time of the work. The D.S. lab receives funds from a collaboration agreement between CNIC and Inmunotek. The other authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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