Zhao Zhanqin, Xue Yun, Tang Xibiao, Wu Bin, Cheng Xiangchao, He Qigai, Zhang Chunjie, Guo Aizhen, Jin Meilin, Chen Huanchun
Huazhong Agricultural University, Wuhan, Hubei, China.
Vaccine. 2009 Apr 21;27(18):2523-8. doi: 10.1016/j.vaccine.2008.09.091. Epub 2008 Oct 11.
Bordetella bronchiseptica is a Gram-negative respiratory pathogen that causes substantial disease in a variety of animals. Filamentous hemagglutinin (FHA) and pertactin are important attachment factors and protective immunogens, which serve as protective antigens in several animal models of infection with B. bronchiseptica. Here, we showed the efficacy of subcutaneous immunization of mice with a recombinant protein rF1P2, which consisted of the important immunodominant protective type I domain (F1) of FHA and the highly immunogenic region II domain (P2) of pertactin. Groups of mice tested, when challenged with different strains of B. bronchiseptica were fully protected, with long-lasting immunity to lethal B.bronchiseptica challenge, whereas mice immunized with Freund's adjuvant alone or PBS were not. In rF1P2-immunized mice, specific antibodies lasted for more than 120 days, and the IgG1/IgG2a ratio remained at a constant level till the end of the study. This suggests that rF1P2-induced a long-lasting balanced humoral immune responses and immunological memory in mice. rF1P2-specific antisera inhibited hemagglutination associated with full-length mature FHA. Furthermore, passive antiserum transfer from immunized animals completely protected naive mice from subsequent B. bronchiseptica challenge. These data may have implications for the development of safe and efficacious subunit vaccines for the prevention of bordetellosis, and may contribute to future acellular whooping cough vaccines.
支气管败血波氏杆菌是一种革兰氏阴性呼吸道病原体,可在多种动物中引发严重疾病。丝状血凝素(FHA)和百日咳杆菌黏附素是重要的黏附因子和保护性免疫原,在支气管败血波氏杆菌感染的多种动物模型中作为保护性抗原。在此,我们展示了用重组蛋白rF1P2对小鼠进行皮下免疫的效果,该重组蛋白由FHA重要的免疫显性保护性I型结构域(F1)和百日咳杆菌黏附素的高免疫原性II型结构域(P2)组成。当用不同菌株的支气管败血波氏杆菌攻击时,受试小鼠组得到了完全保护,对致死性支气管败血波氏杆菌攻击具有持久免疫力,而仅用弗氏佐剂或PBS免疫的小鼠则没有。在rF1P2免疫的小鼠中,特异性抗体持续超过120天,IgG1/IgG2a比值直至研究结束都保持在恒定水平。这表明rF1P2在小鼠中诱导了持久的平衡体液免疫反应和免疫记忆。rF1P2特异性抗血清抑制了与全长成熟FHA相关的血凝反应。此外,来自免疫动物的被动抗血清转移完全保护了未免疫小鼠免受随后的支气管败血波氏杆菌攻击。这些数据可能对开发用于预防博德特氏菌病的安全有效的亚单位疫苗有启示作用,并可能有助于未来的无细胞百日咳疫苗。