Oral Vaccination with Heat Inactivated Mycobacterium bovis Activates the Complement System to Protect against Tuberculosis

PLoS ONE publish this investigation article

May 19^th, 2014

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

Beltran-Beck B., de la Fuente J., Garrido JM., Aranaz A., Sevilla I., Villar M., Boadella M., Galindo RC., Perez de la Lastra JM., Moreno-Cid JA., Fernandez de Mera IG., Alberdi P., Santos G., Ballesteros C., Lyashchenko KP., Minguijon E., Romero B., de Juan L., Dominguez L., Juste R. and Gortazar C.

Oral Vaccination with Heat Inactivated Mycobacterium bovis Activates the Complement System to Protect against Tuberculosis

Participants:

	Sanidad y Biotecnología (SaBio). Instituto de Investigación en Recursos Cinegéticos (IREC). Universidad de Castilla La Mancha (UCLM). Consejo Superior de Investigaciones Científicas (CSIC). Gobierno de Castilla-La Mancha (JCCM).

	Center for Veterinary Health Sciences (CVHS). Oklahoma State University (OSU).

	Instituto Vasco de Investigación y Desarrollo Agrario (NEIKER).

	Chembio Diagnostic Systems Inc.

	Servicio de Micobacterias (MYC). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).

	Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM).

FACTOR	YEAR	Q
2.776	2018	2º

Oral Vaccination with Heat Inactivated Mycobacterium bovis Activates the Complement System to Protect against Tuberculosis

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Oral Vaccination with Heat Inactivated Mycobacterium bovis Activates the Complement System to Protect against Tuberculosis