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

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.

Antibodies generated against dextransucrase exhibit potential anticariostatic properties in Streptococcus mutans

“…It is also assumed that besides S. mutans, other oral bacteria also play a role in the pathogenesis of dental caries although the mechanism is not established. Nevertheless, the inhibitory effect of dextransucrase antibodies against several cariogenic factors of S. mutans may be helpful in formulating strategies to combat the disease (Alam et al 2018). Present data showed that the antibodies generated did not cross react with protein extracts from the liver, heart, lungs and kidneys of mice, rat and rabbit by western blot analysis.…”

“…It has been shown that many bacteria are involved in the genesis of caries formation at different stages. Among these Streptococcus mutans is the primary causative agent of dental caries (Alam et al 2018).…”

“…A number of compounds such as penicillin, cationic agents (chlorhexidine), plant products (polyphenols, flavonoids, anionic agents (sodium dodecyl sulphate) and non-ionic agents (triclosan) have been used for the prevention of dental caries by inhibiting growth and adherence of these cariogenic bacteria to the tooth surface (Jarvinen et al 1993;Chen and Wang 2010). But these organisms are either resistant to them (Alam et al 2018;Bhattacharya et al 2003) or the drugs exhibit side effects (Craig 1998).…”

“…Many surface molecules of S. mutans such as lipoteichoic acid, glucosyltransferases (GTFs), antigen A (a 29-kDa protein antigen), antigen C (a 70-kDa protein antigen), antigen D (a 13-kDa protein antigen), AgI/II (a 190-kDa protein), AgIII (39-kDa protein), GbP (glucan-binding protein) (Kruger 2004), GtfB (Kim et al 2012) and DNA-based active vaccines, synthetic peptides and mucosal adjuvants (heat-labile enterotoxins (HLT) from Vibrio cholera (LT-I) or Escherichia coli (LT-II), bupivacaine, chitosan) have attracted great attention for passive immunisation in the prevention of the dental caries (Yan 2013;Chen and Wang 2010;Fan et al 2002;Xu et al 2007;Alam et al 2018). Fusion vaccines (pGJA-p/VAX and pGJG/GAC/VAX) encoding PAc and GLU of S. mutans were also tested in gnobiotic animals (Kt et al 2013) and flagellin-PAc fusion protein (KF-rPAc) was also tested in rats for anticaries vaccine (Bao et al 2015).…”

pH dependent effects of sodium ions on dextransucrase activity in Streptococcus mutans

“…Streptococcus mutans is a gram positive organism which has been implicated in the pathogenesis of dental caries in humans [1]. The organism produces dextransucrase (E.C.2.4.1.5.)…”