Oral vaccination with heat inactivated Mycobacterium bovis activates the complement system to protect against tuberculosis.
Tuberculosis (TB) remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV). Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs) in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar.
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain.
Beatriz
B
Beltrán-Beck
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.
José
J
de la Fuente
NEIKER-Tecnalia, Animal Health Department, C/Berreaga 1, Derio, Bizkaia, Spain.
Joseba M
JM
Garrido
Dept. Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
Alicia
A
Aranaz
NEIKER-Tecnalia, Animal Health Department, C/Berreaga 1, Derio, Bizkaia, Spain.
Iker
I
Sevilla
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain.
Margarita
M
Villar
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain.
Mariana
M
Boadella
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.
Ruth C
RC
Galindo
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain.
José M
JM
Pérez de la Lastra
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain.
Juan A
JA
Moreno-Cid
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain.
Isabel G
IG
Fernández de Mera
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain.
Pilar
P
Alberdi
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain.
Gracia
G
Santos
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain.
Cristina
C
Ballesteros
Chembio Diagnostic Systems Inc., Medford, New York, United States of America.
Konstantin P
KP
Lyashchenko
NEIKER-Tecnalia, Animal Health Department, C/Berreaga 1, Derio, Bizkaia, Spain.
Esmeralda
E
Minguijón
Centro de Vigilancia Sanitaria Veterinaria (VISAVET), Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
Beatriz
B
Romero
Centro de Vigilancia Sanitaria Veterinaria (VISAVET), Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
Lucía
L
de Juan
Centro de Vigilancia Sanitaria Veterinaria (VISAVET), Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
Lucas
L
Domínguez
NEIKER-Tecnalia, Animal Health Department, C/Berreaga 1, Derio, Bizkaia, Spain.
Ramón
R
Juste
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain.
Christian
C
Gortazar
D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D015153:Blotting, Western; D003165:Complement System Proteins / Q000187:drug effects*; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D009163:Mycobacterium bovis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D040901:Proteomics; D060888:Real-Time Polymerase Chain Reaction; D012044:Regression Analysis; D034421:Sus scrofa; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000494:pharmacology*
D000907:Antibodies, Bacterial; D017931:DNA Primers; D015164:Vaccines, Inactivated; D003165:Complement System Proteins