PDF(Pubmed)
Abstract：
Bordetella pertussis, the bacterium responsible for whooping cough, remains a significant public health challenge despite the existing licensed pertussis vaccines. Current acellular pertussis vaccines, though having favorable reactogenicity and efficacy profiles, involve complex and costly production processes. In addition, acellular vaccines have functional challenges such as short-lasting duration of immunity and limited antigen coverage. Filamentous hemagglutinin (FHA) is an adhesin of B. pertussis that is included in all multivalent pertussis vaccine formulations. Antibodies to FHA have been shown to prevent bacterial attachment to respiratory epithelial cells, and T cell responses to FHA facilitate cell-mediated immunity. In this study, FHA\'s mature C-terminal domain (MCD) was evaluated as a novel vaccine antigen. MCD was conjugated to virus-like particles via SpyTag-SpyCatcher technology. Prime-boost vaccine studies were performed in mice to characterize immunogenicity and protection against the intranasal B. pertussis challenge. MCD-SpyVLP was more immunogenic than SpyTag-MCD antigen alone, and in Tohama I strain challenge studies, improved protection against challenge was observed in the lungs at day 3 and in the trachea and nasal wash at day 7 post-challenge. Furthermore, a B. pertussis strain encoding genetically inactivated pertussis toxin was used to evaluate MCD-SpyVLP vaccine immunity. Mice vaccinated with MCD-SpyVLP had significantly lower respiratory bacterial burden at both days 3 and 7 post-challenge compared to mock-vaccinated animals. Overall, these data support the use of SpyTag-SpyCatcher VLPs as a platform for use in vaccine development against B. pertussis and other pathogens.
摘要：
百日咳杆菌,导致百日咳的细菌,尽管现有许可的百日咳疫苗仍是一个重大的公共卫生挑战.目前的无细胞百日咳疫苗，虽然具有良好的反应原性和功效谱，涉及复杂和昂贵的生产过程。此外,无细胞疫苗具有功能性挑战,例如短持续时间的免疫和有限的抗原覆盖。丝状血凝素(FHA)是百日咳杆菌的粘附素,其包括在所有多价百日咳疫苗制剂中。FHA的抗体已被证明可以防止细菌附着在呼吸道上皮细胞上，和T细胞对FHA的应答促进细胞介导的免疫。在这项研究中,FHA的成熟C端结构域（MCD）被评估为新型疫苗抗原。MCD通过SpyTag-SpyCatcher技术与病毒样颗粒缀合。在小鼠中进行初始-加强疫苗研究以表征免疫原性和针对鼻内百日咳博德特氏菌攻击的保护。MCD-SpyVLP比单独的SpyTag-MCD抗原更具免疫原性，在Tohama，我紧张挑战研究，在第3天的肺中以及在攻击后第7天的气管和鼻洗液中观察到了改善的针对攻击的保护。此外，编码基因灭活百日咳毒素的百日咳博德特氏菌菌株用于评估MCD-SpyVLP疫苗免疫。与模拟接种的动物相比,用MCD-SpyVLP接种的小鼠在攻击后第3天和第7天具有显著更低的呼吸道细菌负荷。总的来说,这些数据支持使用SpyTag-SpyCatcherVLP作为平台,用于开发针对百日咳杆菌和其他病原体的疫苗.
