Abstract
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.
Highlights
Streptococcus mutans and Streptococcus sobrinus are the main causative agents of human dental caries
Passive immunization by applying mucosal vaccinations such as S. mutans and S. sobrinus antigens GTFs, antigen I/II, glucan-binding proteins (GBP), and virulence-associated immunomodulatory extracellular proteins (VIP) at inductive sites leads to increases in IgA secretion and can be effective in preventing caries formation[18,21]
We obtained Fabs that bound to S. mutans and S. sobrinus, blocked biofilm formation in vitro, and prevented dental caries formation in rat caries model
Summary
OPEN Synthetic antigen-binding fragments (Fabs) against S. mutans and S. sobrinus inhibit caries. 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. Passive immunization by applying mucosal vaccinations such as S. mutans and S. sobrinus antigens GTFs, antigen I/II, GBP, and virulence-associated immunomodulatory extracellular proteins (VIP) at inductive sites leads to increases in IgA secretion and can be effective in preventing caries formation[18,21]. By selecting the Fab-phage library against live bacteria, we were able to generate Fabs against antigens presented in their native context in an unbiased manner Using this strategy, we obtained Fabs that bound to S. mutans and S. sobrinus, blocked biofilm formation in vitro, and prevented dental caries formation in rat caries model
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