Pulmonary but not subcutaneous vaccination confers protection to TB susceptible mice by an IL17-dependent mechanism.

Aguiló, N (Universidad de Zaragoza) ; Álvarez-Arguedas, S (Universidad de Zaragoza) ; Uranga, S (Universidad de Zaragoza) ; Marinova, D (Universidad de Zaragoza) ; Monzón, M (Universidad de Zaragoza) ; Badiola, J (Universidad de Zaragoza) ; Martín, C (Universidad de Zaragoza)

Resumen: Some of the most promising novel tuberculosis vaccine strategies currently under development are based on respiratory vaccination, mimicking the natural route of infection. In this work, we have compared pulmonary and subcutaneous delivery of BCG vaccine in the tuberculosis-susceptible DBA/2 mouse strain, a model in which parenterally administered BCG vaccine does not protect against tuberculosis. Our data show that intranasally but not subcutaneously administered BCG confers robust protection against pulmonary tuberculosis challenge. In addition, our results indicate that pulmonary vaccination triggers a Mycobacterium tuberculosis–specific mucosal immune response orchestrated by interleukin 17A (IL-17A). Thus, IL-17A neutralization in vivo reduces protection and abrogates M. tuberculosis–specific immunoglobulin A (IgA) secretion to respiratory airways and lung expression of polymeric immunoglobulin receptor induced following intranasal vaccination. Together, our results demonstrate that pulmonary delivery of BCG can overcome the lack of protection observed when BCG is given parenterally, suggesting that respiratory tuberculosis vaccines could have an advantage in tuberculosis-endemic countries, where intradermally administered BCG has inefficient effectiveness against pulmonary tuberculosis.

Idioma: Inglés

DOI: 10.1093/infdis/jiv503

Año: 2016

Publicado en: JOURNAL OF INFECTIOUS DISEASES 213, 5 (2016), 831-839
ISSN: 0022-1899

Factor impacto JCR: 6.273 (2016)

Categ. JCR: IMMUNOLOGY rank: 23 / 150 = 0.153 (2016) - Q1 - T1
Categ. JCR: MICROBIOLOGY rank: 15 / 124 = 0.121 (2016) - Q1 - T1
Categ. JCR: INFECTIOUS DISEASES rank: 7 / 84 = 0.083 (2016) - Q1 - T1

Factor impacto SCIMAGO: 3.931 - Infectious Diseases (Q1) - Immunology and Allergy (Q1)

Financiación: info:eu-repo/grantAgreement/EC/H2020/643381/EU/TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development/TBVAC2020
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P

Tipo y forma: Article (PostPrint)

Área (Departamento): Área Microbiología (Dpto. Microb.Med.Pr.,Sal.Públ.)
Área (Departamento): Area Histología (Dpto. Anatom.Histolog.Humanas)
Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)
Área (Departamento): Proy. investigación HQA (Dpto. Microb.Med.Pr.,Sal.Públ.)