Immunology platform, Analytical Sciences North America, Sanofi Pasteur, Toronto, ON, Canada.
Front Immunol. 2020 Dec 15;11:605273. doi: 10.3389/fimmu.2020.605273. eCollection 2020.
The pertussis vaccination is highly recommended for infants, children, and pregnant women. Despite a high coverage of vaccination, pertussis continues to be of public health concern as a re-emerging infectious disease. The mechanism by which vaccine-elicited anti-pertussis antibodies mediate direct bactericidal effects is poorly understood. In this study, we showed that the interaction of with A549 epithelial cells induce release of biological factors which enhance bacteria growth. Complement-depleted antisera from vaccine-immunized guinea pigs or monoclonal antibodies targeting FHA and FIM mediate bacteria aggregation and elicit bactericidal effects. Our results indicated that aggregation of bacteria through anti-FIM and anti-FHA specific antibodies is one of the major biological mechanisms to clear bacterial infections and restore epithelial cell survival . Our data also indicates that the anti-pertussis antibodies reduce secretion of proinflammatory chemokines and cytokines by preventing interaction of with host cells. The results of this study not only demonstrate mechanism of action of anti-FIM and anti-FHA antibodies, but also opens translational applications for potential therapeutic approaches or development of analytical assays such as potency assays.
百日咳疫苗高度推荐给婴儿、儿童和孕妇使用。尽管疫苗接种率很高，但百日咳作为一种重新出现的传染病，仍然是公共卫生关注的问题。疫苗引起的抗百日咳抗体介导直接杀菌作用的机制尚不清楚。在这项研究中，我们表明与 A549 上皮细胞的相互作用诱导释放了增强细菌生长的生物因子。用疫苗免疫豚鼠的补体耗尽抗血清或针对 FHA 和 FIM 的单克隆抗体可介导细菌聚集并引发杀菌作用。我们的结果表明，通过抗 FIM 和抗 FHA 特异性抗体聚集细菌是清除细菌感染和恢复上皮细胞存活的主要生物学机制之一。我们的数据还表明，抗百日咳抗体通过阻止与宿主细胞的相互作用，减少促炎趋化因子和细胞因子的分泌。这项研究的结果不仅证明了抗 FIM 和抗 FHA 抗体的作用机制，还为潜在的治疗方法或分析测定（如效价测定）的开发打开了转化应用的可能性。
