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Active and Passive Immunizations with Bordetella Colonization Factor A Protect Mice against Respiratory Challenge with Bordetella bronchiseptica

机译:博德特氏菌定殖因子A的主动和被动免疫保护小鼠免受支气管败血性博德特氏菌的呼吸挑战

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Bordetella colonization factor A (BcfA) is an outer membrane immunogenic protein, which is critical for efficient colonization of the murine respiratory tract. These properties of BcfA prompted us to examine its utility in inducing a protective immune response against Bordetella bronchiseptica in a mouse model of intranasal infection. Mice vaccinated with BcfA demonstrated reduced pathology in the lungs and harbored lower bacterial burdens in the respiratory tract. Immunization with BcfA led to the generation of BcfA-specific antibodies in both the sera and lungs, and passive immunization led to the reduction of B. bronchiseptica in the tracheas and lungs. These results suggest that protection after immunization with BcfA is mediated in part by antibodies against BcfA. To further investigate the mechanism of BcfA-induced immune clearance, we examined the role of neutrophils and macrophages. Our results demonstrate that neutrophils are critical for anti-BcfA antibody-mediated clearance and that opsonization with anti-BcfA serum enhances phagocytosis of B. bronchiseptica by murine macrophages. We show that immunization with BcfA results in the production of gamma interferon and subclasses of immunoglobulin G antibodies that are consistent with the induction of a Th1-type immune response. In combination, our findings suggest that the mechanism of BcfA-mediated immunity involves humoral and cellular responses. Expression of BcfA is conserved among multiple clinical isolates of B. bronchiseptica. Our results demonstrate the striking protective efficacy of BcfA-mediated immunization, thereby highlighting its utility as a potential vaccine candidate. These results also provide a model for the development of cell-free vaccines against B. bronchiseptica.
机译: Bordetella c lononization f actor A (BcfA)是一种外膜免疫原性蛋白,对鼠呼吸道的有效定殖至关重要。 BcfA的这些特性促使我们研究其在鼻内感染小鼠模型中诱导针对支气管败血博德特氏菌的保护性免疫应答的效用。接种BcfA的小鼠表现出肺部病变减少,呼吸道细菌负担降低。 BcfA免疫导致血清和肺中BcfA特异性抗体的产生,被动免疫导致Bem的减少。气管和肺中的支气管败血病。这些结果表明,用BcfA免疫后的保护部分地由针对BcfA的抗体介导。为了进一步研究BcfA诱导的免疫清除的机制,我们检查了中性粒细胞和巨噬细胞的作用。我们的结果表明,中性粒细胞对于抗BcfA抗体介导的清除至关重要,并且与抗BcfA血清进行调理作用可增强 B的吞噬作用。鼠巨噬细胞对支气管败血病的诊断我们显示,用BcfA免疫可导致产生γ干扰素和免疫球蛋白G抗体亚类,这些抗体与Th1型免疫应答的诱导相一致。总之,我们的发现表明,BcfA介导的免疫机制涉及体液和细胞反应。 BcfA的表达在多个B型临床分离株中是保守的。支气管败血病。我们的结果证明了BcfA介导的免疫的惊人保护作用,从而突出了其作为潜在疫苗候选者的效用。这些结果也提供了开发针对 B的无细胞疫苗的模型。支气管败血病

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