Oral Administration as an Alternative Route for Sustained-Release Hydrogel-Encapsulated Anti-Caries Gene Vaccine (Preprint)

This is the authors' abstract. We don't add key points for this paper.

UNSTRUCTURED Streptococcus mutans (S. mutans) is the primary pathogenic bacterium causing dental caries, and the protein antigen (SpaP) of its P region and the glucan-binding protein (Gbp) with glucan-binding domain (GBD) exhibit promising immunogenicity. They have been separately utilized in the development of anti-caries vaccines, but their effectiveness needs enhancement. To improve the immune response and address challenges in the acidic gastrointestinal environment, such as antigen degradation, mucosal barriers, inefficient cellular absorption by immune cells, and rapid enzymatic degradation of vaccines, this study aims to create an innovative anti-caries vaccine using a temperature-sensitive sustained-release hydrogel as a carrier and evaluate the vaccine's immune response both in vitro and in vivo. In this study, we successfully connected the antigens of the P region of the recombinant protein SpaP from S. mutans and the glucan-binding domain (GBD) of GbpA. Using a sustained-release temperature-sensitive hydrogel, PLGA-PEG-PLGA, as a carrier, the anti-caries vaccine pVAX1-SPG was prepared. Initially, the sustained-release effect of the anti-caries vaccine was observed in vitro. Subsequently, rabbits were immunized orally and by injection to evaluate the vaccine's immune response and conduct general safety testing. pVAX1-SPG improved vaccine release in vitro, maintaining efficacy for a longer duration. In rabbits, it induced an elevation of SpaP-specific serum IgG and saliva IgA antibodies. Moreover, orally administered pVAX1-SPG induced stronger SpaP-specific serum IgG and saliva IgA antibodies than the injection route. No abnormalities were detected in various safety indicators. The temperature-sensitive sustained-release hydrogel-encapsulated pVAX1-SPG anti-caries gene vaccine can elicit a significantly effective and long-term immune response. The oral route proves to be a more readily accepted and safer alternative, holding enormous potential in the prevention and treatment of dental caries.