Oral administration as an alternative route for sustained-release hydrogel-encapsulated anti-caries gene vaccine

Abstract Background Streptococcus mutans (S. mutans) is the primary pathogenic bacterium causing dental caries. The P region of surface protein antigen P (SpaP) and the glucan-binding protein A (GbpA) harboring the glucan-binding domain (GBD) exhibit promising immunogenicity. To improve immune response and overcome challenges such as antigen degradation in the acidic gastrointestinal environment, mucosal barriers, inefficient cellular uptake, and rapid enzymatic degradation, this study aimed to construct a novel anti-caries vaccine using a temperature-sensitive sustained-release hydrogel as a carrier and evaluate its immune response in vitro and in vivo. Methods The P-region antigen of recombinant SpaP and the glucan-binding domain (GBD) of GbpA were linked. The anti-caries vaccine pVAX1-SPG was formulated with the temperature-sensitive sustained-release hydrogel poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA). In vitro sustained release was observed. Rabbits were immunized orally or by injection to assess immune response and safety. Results The pVAX1-SPG-loaded hydrogel exhibited sustained plasmid release in vitro. Immunized rabbits showed elevated levels of SpaP-specific serum IgG and salivary IgA. Oral vaccination elicited stronger salivary IgA responses at several time points than intramuscular administration, whereas intramuscular administration induced comparable or higher serum IgG levels at several time points. No apparent adverse reactions were observed throughout the animal experiments. Conclusions Oral administration of the hydrogel-encapsulated pVAX1-SPG anti-caries gene vaccine elicited robust and sustained salivary IgA and serum IgG responses in rabbits. No overt toxicity was observed under the conditions of this study. These findings support its potential as a needle-free strategy for dental caries prevention, although dedicated biodistribution and long-term safety studies are warranted.