000099762 001__ 99762
000099762 005__ 20230519145405.0
000099762 0247_ $$2doi$$a10.1016/j.ebiom.2020.103186
000099762 0248_ $$2sideral$$a123292
000099762 037__ $$aART-2021-123292
000099762 041__ $$aeng
000099762 100__ $$0(orcid)0000-0002-3086-3013$$aTarancón, R.
000099762 245__ $$aTherapeutic efficacy of pulmonary live tuberculosis vaccines against established asthma by subverting local immune environment
000099762 260__ $$c2021
000099762 5060_ $$aAccess copy available to the general public$$fUnrestricted
000099762 5203_ $$aBackground: Substantial recent advances in the comprehension of the molecular and cellular mechanisms behind asthma have evidenced the importance of the lung immune environment for disease outcome, making modulation of local immune responses an attractive therapeutic target against this pathology. Live attenuated mycobacteria, such as the tuberculosis vaccine BCG, have been classically linked with a type 1 response, and proposed as possible modulators of the type 2 response usually associated with asthma.
Methods: In this study we used different acute and chronic murine models of asthma to investigate the therapeutic efficacy of intranasal delivery of the live tuberculosis vaccines BCG and MTBVAC by regulating the lung immune environment associated with airway hyperresponsiveness (AHR).
Findings: Intranasal administration of BCG, or the novel tuberculosis vaccine candidate MTBVAC, abrogated AHR-associated hallmarks, including eosinophilia and lung remodeling. This correlated with the re-polarization of allergen-induced M2 macrophages towards an M1 phenotype, as well as with the induction of a strong allergen-specific Th1 response. Importantly, vaccine treatment was effective in a scenario of established chronic asthma where a strong eosinophil infiltration was already present prior to immunization. We finally compared the nebulization efficiency of clinical formulations of MTBVAC and BCG using a standard commercial nebulizer for potential aerosol application.
Interpretation: Our results demonstrate that pulmonary live tuberculosis vaccines efficiently revert established asthma in mice. These data support the further exploration of this approach as potential therapy against asthma.
000099762 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII-DGA-FSE-UZ/JIUZ-2018-BIO-01$$9info:eu-repo/grantAgreement/ES/MCIU/RTI2018-097625-B-I00$$9info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P
000099762 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000099762 590__ $$a11.205$$b2021
000099762 592__ $$a2.663$$b2021
000099762 594__ $$a15.0$$b2021
000099762 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b14 / 140 = 0.1$$c2021$$dQ1$$eT1
000099762 593__ $$aMedicine (miscellaneous)$$c2021$$dQ1
000099762 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2021$$dQ1
000099762 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000099762 700__ $$aMata, E.$$uUniversidad de Zaragoza
000099762 700__ $$0(orcid)0000-0001-7866-2803$$aUranga, S.$$uUniversidad de Zaragoza
000099762 700__ $$0(orcid)0000-0002-9713-2127$$aGómez, A.B.$$uUniversidad de Zaragoza
000099762 700__ $$0(orcid)0000-0001-8644-120X$$aMarinova, D.$$uUniversidad de Zaragoza
000099762 700__ $$0(orcid)0000-0003-1027-7583$$aOtal, I.$$uUniversidad de Zaragoza
000099762 700__ $$0(orcid)0000-0003-2993-5478$$aMartín, C.$$uUniversidad de Zaragoza
000099762 700__ $$0(orcid)0000-0001-7897-9173$$aAguiló, N.$$uUniversidad de Zaragoza
000099762 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología
000099762 7102_ $$11011$$2X$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cProy. investigación HQA
000099762 773__ $$g(2021), 103186 [14 pp]$$pEBioMedicine$$tEBioMedicine$$x2352-3964
000099762 8564_ $$s588658$$uhttps://zaguan.unizar.es/record/99762/files/texto_completo.pdf$$yVersión publicada
000099762 8564_ $$s2584881$$uhttps://zaguan.unizar.es/record/99762/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
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000099762 951__ $$a2023-05-18-13:45:41
000099762 980__ $$aARTICLE