Therapeutic Efficacy of Pulmonary Live Tuberculosis Vaccines Against Established Asthma by Subverting Local Immune Environment

Overview

Journal EBioMedicine

Specialty Biomedical Engineering

Date 2021 Jan 22

PMID 33478923

Citations 4

Authors

Raquel Tarancon

Elena Mata

Santiago Uranga

Ana Belen Gomez

Dessislava Marinova

Isabel Otal

Carlos Martin

Nacho Aguilo

Affiliations

Soon will be listed here.

Abstract

Background: Substantial recent advances in the comprehension of the molecular and cellular mechanisms behind asthma have evidenced the importance of the lung immune environment for disease outcome, making modulation of local immune responses an attractive therapeutic target against this pathology. Live attenuated mycobacteria, such as the tuberculosis vaccine BCG, have been classically linked with a type 1 response, and proposed as possible modulators of the type 2 response usually associated with asthma.

Methods: In this study we used different acute and chronic murine models of asthma to investigate the therapeutic efficacy of intranasal delivery of the live tuberculosis vaccines BCG and MTBVAC by regulating the lung immune environment associated with airway hyperresponsiveness (AHR).

Findings: Intranasal administration of BCG, or the novel tuberculosis vaccine candidate MTBVAC, abrogated AHR-associated hallmarks, including eosinophilia and lung remodeling. This correlated with the re-polarization of allergen-induced M2 macrophages towards an M1 phenotype, as well as with the induction of a strong allergen-specific Th1 response. Importantly, vaccine treatment was effective in a scenario of established chronic asthma where a strong eosinophil infiltration was already present prior to immunization. We finally compared the nebulization efficiency of clinical formulations of MTBVAC and BCG using a standard commercial nebulizer for potential aerosol application.

Interpretation: Our results demonstrate that pulmonary live tuberculosis vaccines efficiently revert established asthma in mice. These data support the further exploration of this approach as potential therapy against asthma.

Funding: Spanish Ministry of Science [grant numbers: BIO2014-5258P, RTI2018-097625-B-I00], Instituto de Salud Carlos III, Gobierno de Aragón/Fondo Social Europeo, University of Zaragoza [grant number: JIUZ-2018-BIO-01].

Citing Articles

Correlation between systemic allergen desensitisation and long-term asthma protection in mice following intravenous administration of the live tuberculosis vaccine MTBVAC.

Calvo S, Rodrigo-Munoz J, Tarancon R, Uranga S, Martin C, Del Pozo V EBioMedicine. 2024; 107:105272.

PMID: 39173529 PMC: 11387674. DOI: 10.1016/j.ebiom.2024.105272.

Repurposing mucosal delivery devices for live attenuated tuberculosis vaccines.

Puri M, Miranda-Hernandez S, Subbian S, Kupz A Front Immunol. 2023; 14:1159084.

PMID: 37063870 PMC: 10098179. DOI: 10.3389/fimmu.2023.1159084.

TIPICO XI: report of the first series and podcast on infectious diseases and vaccines (aTIPICO).

Martinon-Torres F, Garcia-Sastre A, Pollard A, Martin C, Osterhaus A, Ladhani S Hum Vaccin Immunother. 2021; 17(11):4299-4327.

PMID: 34762551 PMC: 8828069. DOI: 10.1080/21645515.2021.1953351.

Construction of a prognostic signature of autophagy-related lncRNAs in non-small-cell lung cancer.

Zhang X, Cao Y, Chen L BMC Cancer. 2021; 21(1):921.

PMID: 34391383 PMC: 8364711. DOI: 10.1186/s12885-021-08654-2.

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