Synthetic antigen-binding fragments (Fabs) against S. mutans and S. sobrinus inhibit caries formation.

Synthetic antigen-binding fragments (Fabs) against S. mutans and S. sobrinus inhibit caries formation.
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DOI:
10.1038/s41598-018-28240-0
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发表时间:
2018-07-05
期刊:
影响因子:
4.6
通讯作者:
Geyer CR
Geyer CR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Alam MK;Zheng L;Liu R;Papagerakis S;Papagerakis P;Geyer CR

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变形链球菌和远缘链球菌是人类龋病的主要致病菌。目前治疗龋齿的策略是昂贵的,并且不能完全根除它们。使用针对链球菌表面抗原的非人抗体的被动免疫在人体试验中已显示成功,然而它们经常引起免疫反应。我们利用噬菌体展示技术制备了抗沙门氏菌的人源抗原结合片段(Fab)。和S.远缘的这些Fab在E.大肠杆菌并结合到表面S。和S.远缘的Fab对蔗糖诱导的S.和S. sobrinus生物被膜的体外形成及与S.和S. sobrinus Fabs在大鼠龋齿模型中预防龋齿形成。实验结果表明S.和S.远缘Fab可用于被动免疫预防龋齿。将来,该策略可应用于龋齿治疗,其中Fabs被局部应用于牙齿表面。
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.
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