000144879 001__ 144879 000144879 005__ 20250923084418.0 000144879 0247_ $$2doi$$a10.1016/j.ebiom.2024.105272 000144879 0248_ $$2sideral$$a139683 000144879 037__ $$aART-2024-139683 000144879 041__ $$aeng 000144879 100__ $$aCalvo, Silvia 000144879 245__ $$aCorrelation between systemic allergen desensitisation and long-term asthma protection in mice following intravenous administration of the live tuberculosis vaccine MTBVAC 000144879 260__ $$c2024 000144879 5060_ $$aAccess copy available to the general public$$fUnrestricted 000144879 5203_ $$aBackground MTBVAC is a live attenuated tuberculosis vaccine, currently undergoing phase III evaluation for tuberculosis prevention. In previous preclinical studies, we found that local pulmonary administration of MTBVAC via the intranasal route had a strong therapeutic effect against asthma. This effect correlated with the abrogation of allergen-specific Th2 response in the lungs. Methods Using different mouse models of asthma, we investigated the effect of MTBVAC administered by intravenous (IV) route and its potential as immunotherapeutic agent to induce desensitisation of allergen-specific responses at a systemic level. We explored the effects of this process in the efficacy against airway hyperresponsiveness (AHR) induced by exposure to different allergens. Findings IV MTBVAC was highly efficient at reducing AHR induced by different allergens. Additionally, IV MTBVAC was found to be well-tolerated, being progressively eliminated from the different organs analysed. From a mechanistic standpoint, we observed that MTBVAC intravenous, but not intranasal, impaired allergen-specific Th2 response in both lungs and spleen. This reduction at a systemic level correlated with long-term therapeutic protection against allergen exposure. Our results also revealed differential immunological mechanisms governing systemic and local pulmonary allergen desensitisation processes. Notably, in a cohort of patients with asthma sensitive to house dust mite (HDM), in vitro incubation of peripheral blood mononuclear cells (PBMCs) with MTBVAC prevented allergen-specific production of Th2 cytokines IL-4 and IL-5. Interpretation Altogether, our results suggest that intravenous MTBVAC could be a plausible allergen desensitising approach for treatment of asthma, and could provide long-term protection against allergen exposure. 000144879 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/CB06-06-0013$$9info:eu-repo/grantAgreement/ES/ISCIII/CB06-06-0020$$9info:eu-repo/grantAgreement/ES/MICINN/PID2022-138624OB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/RTI2018-097625-B-100 000144879 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ 000144879 590__ $$a10.8$$b2024 000144879 592__ $$a3.591$$b2024 000144879 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b13 / 195 = 0.067$$c2024$$dQ1$$eT1 000144879 593__ $$aMedicine (miscellaneous)$$c2024$$dQ1 000144879 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2024$$dQ1 000144879 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000144879 700__ $$aRodrigo-Muñoz, Jose Manuel 000144879 700__ $$0(orcid)0000-0002-3086-3013$$aTarancón, Raquel 000144879 700__ $$0(orcid)0000-0001-7866-2803$$aUranga, Santiago$$uUniversidad de Zaragoza 000144879 700__ $$0(orcid)0000-0003-2993-5478$$aMartín, Carlos$$uUniversidad de Zaragoza 000144879 700__ $$aPozo, Victoria del 000144879 700__ $$0(orcid)0000-0001-7897-9173$$aAguiló, Nacho$$uUniversidad de Zaragoza 000144879 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología 000144879 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología 000144879 7102_ $$11011$$2X$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cProy. investigación HQA 000144879 773__ $$g107 (2024), 105272 [16 pp.]$$pEBioMedicine$$tEBioMedicine$$x2352-3964 000144879 8564_ $$s3183109$$uhttps://zaguan.unizar.es/record/144879/files/texto_completo.pdf$$yVersión publicada 000144879 8564_ $$s2226977$$uhttps://zaguan.unizar.es/record/144879/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000144879 909CO $$ooai:zaguan.unizar.es:144879$$particulos$$pdriver 000144879 951__ $$a2025-09-22-14:34:04 000144879 980__ $$aARTICLE
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