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Characterization of the protective capacity and immunogenicity of the 69-kD outer membrane protein of Bordetella pertussis

机译:百日咳博德特氏菌69-kD外膜蛋白的保护能力和免疫原性表征

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摘要

Immunization with the 69-kD outer membrane protein (OMP) of Bordetella pertussis protected neonatal mice against lethal respiratory challenge with B. pertussis 18323. Active immunization elicited a serum IgG anti- 69-kD OMP response at the time of challenge, with IgG anti-69-kD OMP antibodies detected in bronchoalveolar lavage fluid after challenge. Intravenous administration of BPE8, a monoclonal IgG1 anti-69-kD OMP, also protected young mice against B. pertussis challenge. Intravenously injected BPE8 was detected in the lungs of mice at the time of aerosol challenge, suggesting that the presence of specific antibody in the lungs may mediate protection. Thus the 69-kD OMP of B. pertussis is a protective antigen in mice that elicits specific serum antibody that can transude to the lung. The 69-kD OMP was detected in a preparation of a Takeda acellular vaccine by immunoblot analysis and a serum antibody response to the 69-kD OMP was observed in 18-mo-old children boosted with this preparation of Japanese acellular vaccine. Our results demonstrate that the B. pertussis 69-kD OMP is a protective antigen in animals, is immunogenic in humans, and is present in a preparation of acellular pertussis vaccine that is widely used in Japan. These findings indicate that the 69-kD OMP should be seriously considered as a candidate for inclusion in new formulations of antigenically defined acellular pertussis vaccines.
机译:百日咳博德特氏菌69-kD外膜蛋白(OMP)的免疫保护了新生小鼠免受百日咳博德特氏菌18323的致死性呼吸道攻击。在攻击时,主动免疫引起血清IgG抗69-kD OMP反应,而IgG抗激发后在支气管肺泡灌洗液中检测到-69-kD OMP抗体。静脉内施用BPE8(一种单克隆IgG1抗69-kD OMP)也可以保护年轻小鼠免受百日咳博德特氏菌的攻击。气雾激发时在小鼠的肺中检测到静脉注射的BPE8,这表明肺中特异性抗体的存在可能介导了保护作用。因此,百日咳博德特氏菌的69-kD OMP是小鼠中的一种保护性抗原,可引发可穿透肺的特异性血清抗体。通过免疫印迹分析在武田无细胞疫苗制剂中检测到69 kD OMP,并在用这种日本无细胞疫苗制剂加强免疫的18岁儿童中观察到对69 kD OMP的血清抗体反应。我们的结果表明,百日咳博德特氏菌69-kD OMP在动物中是一种保护性抗原,在人类中具有免疫原性,并且存在于在日本广泛使用的无细胞百日咳疫苗的制备中。这些发现表明69-kD OMP应该被认真考虑作为抗原定义的脱细胞百日咳疫苗新制剂中的候选药物。

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