Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Room 2841, Royal University Hospital, 103 Hospital Drive, Saskatoon, S7N0W8, Canada.
Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, 1011N University, Ann Arbor, 48109, USA.
Sci Rep. 2018 Jul 5;8(1):10173. doi: 10.1038/s41598-018-28240-0.
Streptococcus mutans and Streptococcus sobrinus are the main causative agents of human dental caries. Current strategies for treating caries are costly and do not completely eradicate them completely. Passive immunization using nonhuman antibodies against Streptococcal surface antigens has shown success in human trials, however they often invoke immune reactions. We used phage display to generate human antigen-binding fragments (Fabs) against S. mutans and S. sobrinus. These Fabs were readily expressed in E. coli and bound to the surface S. mutans and S. sobrinus. Fabs inhibited sucrose-induced S. mutans and S. sobrinus biofilm formation in vitro and a combination of S. mutans and S. sobrinus Fabs prevented dental caries formation in a rat caries model. These results demonstrated that S. mutans and S. sobrinus Fabs could be used in passive immunization strategies to prevent dental caries. In the future, this strategy may be applied towards a caries therapy, whereby Fabs are topically applied to the tooth surface.
变形链球菌和远缘链球菌是人类龋齿的主要病原体。目前治疗龋齿的策略成本高昂,且不能完全将其彻底根除。针对链球菌表面抗原的非人类抗体的被动免疫在人体试验中取得了成功,然而它们常常会引发免疫反应。我们使用噬菌体展示技术生成了针对变形链球菌和远缘链球菌的人源抗原结合片段(Fab)。这些 Fab 可在大肠杆菌中轻易表达,并与变形链球菌和远缘链球菌的表面结合。Fab 可抑制体外蔗糖诱导的变形链球菌和远缘链球菌生物膜形成,且变形链球菌和远缘链球菌 Fab 的组合可预防大鼠龋齿模型中的龋齿形成。这些结果表明,变形链球菌和远缘链球菌 Fab 可用于被动免疫策略以预防龋齿。未来,该策略可能会应用于龋齿治疗,即将 Fab 局部应用于牙齿表面。