Correlation between systemic allergen desensitisation and long-term asthma protection in mice following intravenous administration of the live tuberculosis vaccine MTBVACResearch in context
Silvia Calvo,
Jose Manuel Rodrigo-Muñoz,
Raquel Tarancón,
Santiago Uranga,
Carlos Martín,
Victoria del Pozo,
Nacho Aguiló
Affiliations
Silvia Calvo
Grupo de Genética de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragon, Zaragoza, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
Jose Manuel Rodrigo-Muñoz
CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Immunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain
Raquel Tarancón
Grupo de Genética de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragon, Zaragoza, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
Santiago Uranga
Grupo de Genética de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragon, Zaragoza, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
Carlos Martín
Grupo de Genética de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragon, Zaragoza, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
Victoria del Pozo
CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Immunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain; Universidad Autónoma de Madrid, Madrid, Spain
Nacho Aguiló
Grupo de Genética de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragon, Zaragoza, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Corresponding author. Grupo de Genética de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragon, Zaragoza, Spain.
Summary: Background: 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. Funding: MCIN/AEI/10.13039/501100011033 [grants number RTI2018-097625-B-I00 and PID2022-138624OB-I00]; Consorcio Centro de Investigación Biomédica en Red- (Groups CB06/06/0020 and CB06/06/0013), Instituto de Salud Carlos III.
