title: Immunological and protective effects of diepitopic subunit dental caries vaccines.
abstract: As a prelude to development of broader-spectrum vaccines for dental caries, we explored the immune potential of constructs combining epitopes from mutans streptococcal glucosyltransferases (GTF) and glucan binding protein B (GbpB). Two diepitopic peptide constructs were synthesized in a multiple antigenic peptide (MAP) format. Both constructs contained SYI, a 20-mer GbpB peptide that included a sequence having major histocompatibility complex class II binding characteristics. One diepitopic construct (SYI-CAT) also contained a 22-mer sequence from the catalytic domain of GTF. Another diepitopic construct (SYI-GLU) contained a 22-mer sequence from the glucan binding domain of GTF. To assess the ability of each construct to induce antibody reactive with GbpB and GTF native proteins, rats were injected subcutaneously with SYI-CAT, SYI-GLU, or the constituent monoepitopic constructs. Only the SYI-CAT construct induced significant levels of serum immunoglobulin G (IgG) and IgA antibody to both pathogenesis-associated proteins. Also, immunization with SYI-CAT significantly (P < 0.001) enhanced the antibody response to the CAT peptide. Experiments then compared experimental dental caries after immunization with SYI-CAT, SYI, or CAT MAP constructs, followed by infection with Streptococcus mutans strain SJr. Dental caries were lower in each peptide-immunized group than in the sham-injected group. The level of protection after SYI-CAT immunization was similar to that after immunization with constituent MAP constructs. In another experiment, rats were infected with Streptococcus sobrinus strain 6715 under an identical protocol. Significant protection was observed on buccal surfaces in both SYI-CAT and CAT construct-immunized, but not in the SYI construct-immunized, groups. Thus, addition of the GbpB-derived SYI peptide to the GTF-derived CAT peptide construct not only enhanced the immunological response to CAT and GTF epitopes, but also extended the protective effect of the construct to include both S. mutans and S. sobrinus.
authors.affiliation: Department of Immunology, The Forsyth Institute, 140 The Fenway, Boston, MA 02115, USA. dsmith@forsyth.org
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Smith
authors.forename: William F
authors.initials: WF
authors.lastname: King
authors.forename: Joy
authors.initials: J
authors.lastname: Rivero
authors.forename: Martin A
authors.initials: MA
authors.lastname: Taubman
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003731:Dental Caries / Q000276:immunology / Q000517:prevention & control*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005964:Glucosyltransferases / Q000737:chemistry / Q000276:immunology*; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control; D013295:Streptococcus mutans / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D000939:Epitopes; D006023:Glycoproteins; C439649:IDG-60 protein, Streptococcus mutans; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010455:Peptides; D005964:Glucosyltransferases