Facilitated intranasal induction of mucosal and systemic immunity to mutans streptococcal glucosyltransferase peptide vaccines

Synthetic peptide vaccines which are derived from functional domains of Str eptococcus mutans glucosyltransferases (GTF) have been shown to induce prot ective immunity in Sprague-Dawley rats after subcutaneous injection in the salivary gland region. Since mucosal induction of salivary immunity would b e preferable in humans, we explored methods to induce mucosal antibody in t he rat to the GTF peptide vaccines HDS and HDS-GLU after intranasal adminis tration. Several methods of facilitation of the immune response were studie d: the incorporation of peptides in bioadhesive poly(D,L-lactide-coglycolid e) (PLGA) microparticles, the use of monoepitopic (HDS) or diepitopic (HDS- GLU) peptide constructs, or the use of mucosal adjuvants. Salivary immunogl obulin A (IgA) responses were not detected after intranasal administration of diepitopic HDS-GLU peptide constructs in alum or after incorporation int o PLGA microparticles. However, significant primary and secondary salivary IgA and serum IgG antibody responses to HDS were induced in all rats when c holera holotoxin (CT) or a detoxified mutant Escherichia coli heat-labile e nterotoxin (R192G LT) were intranasally administered with HDS peptide const ructs in PLGA. Coadministration of LT with HDS resulted in predominantly Ig G2a responses in the serum, while coadministration with CT resulted in sign ificant IgG1 and IgG2a responses to HDS. Serum IgG antibody, which was indu ced to the HDS peptide construct by coadministration with these adjuvants, also bound intact mutans streptococcal GTF in an enzyme-linked immunosorben t assay and inhibited its enzymatic activity. Thus, immune responses which are potentially protective for dental caries can be induced to peptide-base d GTF vaccines after mucosal administration if combined with the CT or LT R 192G mucosal adjuvant.