Recombinant Streptococcus mutans glucan-binding protein D (rGbpD) was incorporated into poly(lactic-co-glycolic acid) (PLGA) microspheres which then were surface-coated with chitosan. The microspheres, with a mean diameter of ca. 1.8 mu m, were intranasally administered in rats. There were elevated salivary immunoglobulin A and serum immunoglobulin G antibody responses to rGbpD, as well as lower molar caries scores in immunized animals as compared to sham immunized ones. The chitosan-coated PLGA microspheres are thus potentially useful for antigen delivery in dental caries vaccination.