Pulmonary but Not Subcutaneous Delivery of BCG Vaccine Confers Protection to Tuberculosis-Susceptible Mice by an Interleukin 17-Dependent Mechanism.
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.
Grupo de Genética de Micobacterias, Departamento de Microbiología, Medicina Preventiva, y Salud Pública CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Nacho
N
Aguilo
Grupo de Genética de Micobacterias, Departamento de Microbiología, Medicina Preventiva, y Salud Pública CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Samuel
S
Alvarez-Arguedas
Grupo de Genética de Micobacterias, Departamento de Microbiología, Medicina Preventiva, y Salud Pública CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Santiago
S
Uranga
Grupo de Genética de Micobacterias, Departamento de Microbiología, Medicina Preventiva, y Salud Pública CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Dessislava
D
Marinova
Research Centre for Encephalopathies and Transmissible Emerging Diseases, Universidad de Zaragoza.
Marta
M
Monzón
Research Centre for Encephalopathies and Transmissible Emerging Diseases, Universidad de Zaragoza.
Juan
J
Badiola
Grupo de Genética de Micobacterias, Departamento de Microbiología, Medicina Preventiva, y Salud Pública Servicio de Microbiología, Hospital Universitario Miguel Servet, ISS Aragón, Zaragoza CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Carlos
C
Martin
D000281:Administration, Intranasal; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D007070:Immunoglobulin A / Q000378:metabolism; D007279:Injections, Subcutaneous; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000517:prevention & control*
D001500:BCG Vaccine; D007070:Immunoglobulin A; D020381:Interleukin-17
BCG; IL-17; IgA; mucosal vaccine; tuberculosis-susceptible mice