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

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-Iniesta, Carlos del Fresno, Estanislao Nistal-Villán, Carlos Ardavín, Antonio Nieto, Miguel Casanovas, José Luis Subiza, David Sancho

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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.

Original languageEnglish
Article number110184
JournalCell Reports
Volume38
Issue number1
DOIs
StatePublished - 4 Jan 2022
Externally publishedYes

Keywords

  • Candida albicans
  • human monocytes
  • influenza
  • macrophages
  • mucosal
  • polybacterial immunomodulator
  • respiratory infection
  • trained immunity
  • vaccine
  • viral infection

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