Beltrán-Beck Beatriz, de la Fuente José, Garrido Joseba M, Aranaz Alicia, Sevilla Iker, Villar Margarita, Boadella Mariana, Galindo Ruth C, Pérez de la Lastra José M, Moreno-Cid Juan A, Fernández de Mera Isabel G, Alberdi Pilar, Santos Gracia, Ballesteros Cristina, Lyashchenko Konstantin P, Minguijón Esmeralda, Romero Beatriz, de Juan Lucía, Domínguez Lucas, Juste Ramón, Gortazar Christian
SaBio IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain.
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.
PLoS One. 2014 May 19;9(5):e98048. doi: 10.1371/journal.pone.0098048. eCollection 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.
结核病（TB）仍然是一种全球性大流行病，影响着数十亿人，因此凸显了对新型疫苗的需求。确定疫苗保护的相关因素对于实现这一目标至关重要。在本研究中，我们使用野猪分枝杆菌感染和结核病模型来表征一种新型热灭活牛分枝杆菌疫苗（IV）引发的保护机制。口服IV疫苗导致培养物和病变评分显著降低，尤其是在胸部，这表明IV疫苗可能为结核病控制提供一种新型疫苗，对预防肺部疾病具有特殊影响，而肺部疾病是当前疫苗的局限性之一。口服IV疫苗可诱导适应性抗体反应以及包括补体成分C3和炎性小体在内的固有免疫反应的激活。分枝杆菌DNA/RNA不参与炎性小体激活，但通过一种尚不清楚的机制增加C3的产生。结果还表明，在接种IV疫苗后，由MHC I抗原呈递树突状细胞（DC）激活产生IFN-γ的CD8 + T细胞介导了一种保护机制，而Th1 CD4 + T细胞没有明确作用。这些结果支持DC在通过类似于吞噬细胞对病原体相关分子模式的反应机制触发对IV疫苗的免疫反应中发挥作用，其中C3在抵抗分枝杆菌感染的保护中起核心作用。较高的C3水平可能会增加调理吞噬作用和有效的细菌清除，同时干扰CR3介导的分枝杆菌调理和非调理吞噬作用，这一过程可能会被接种IV疫苗诱导的抗分枝杆菌蛋白特异性抗体增强。这些结果表明，IV疫苗通过新机制在野猪中发挥抗结核病保护作用。
