Coimmunization with complementary glucosyltransferase peptides results in enhanced immunogenicity and protection against dental caries

Peptide constructs from the catalytic (CAT) and glucan-binding (GLU) region s of the mutans streptococcal glucosyltransferase enzymes (GTF) can provide immunity to dental caries infection. A strategy of coimmunization was test ed to determine whether protection could be enhanced. Rats were immunized w ith one of the previously described peptide constructs from the CAT or GLU region of the GTF of mutans streptococci or coimmunized with a combination of these constructs (CAT-GLU). Coimmunized animals demonstrated significant ly higher serum immunoglobulin G (IgG) and salivary IgA antibody levels to CAT or GTF than rats immunized with either construct alone, To assess the f unctional significance of coimmunization with these constructs, animals wer e immunized as above or with Streptococcus sobrinus GTF and then infected w ith S. sobrinus to explore the effects of immunization on immunological, mi crobiological, and disease (dental caries) parameters. Serum antibody from the communized group inhibited S. sobrinus GTF-mediated insoluble glucan sy nthesis in vitro above that of the individual-construct-immunized groups. I mmunization with CAT or GLU constructs resulted in significantly reduced de ntal caries after infection with S. sobrinus compared with sham-immunized a nimals. Coimmunization produced greater reductions in caries than after imm unization with either CAT or GLU. Also, significant elevations in lymphocyt e proliferative responses to CAT, GLU, and GTF were observed after coimmuni zation with CAT-GLU compared with the responses after immunization with the individual constructs. The results suggested that increased numbers of mem ory T cells, which could proliferate to CAT were generated by coimmunizatio n. The experiments support the functional significance of these GTF domains in dental caries pathogenesis and present coimmunization as a simple alter native to intact GTF to enhance protective immunity against cariogenic micr oorganisms.