Daniel J. Smith

Mucosal Vaccines for Dental Diseases

Abstract Dental caries is an infectious disease that occurs in the presence of secretory and systemic immune elements in the oral cavity. Successful experimental attempts to intercept the disease via active immunity have targeted components that participate in the adherence and accumulation of mutans streptococci on the tooth surface. These components, including glucosyltransferase, glucan-binding protein B, and antigen I/II adhesins, have been used to induce protective salivary IgA responses by oral, nasal, gastric, and even rectal routes. Peptide, recombinant, and DNA-based derivatives of these components have also served as antigens that were effective at reducing experimental dental caries. Passive administration of monoclonal IgG, transgenic SIgA/G, and chicken egg yolk IgY with similar antibody specificities has been used with experimental success, as have single-chain variable fragments with anti-adhesin properties expressed on the surface of Lactobacilli. Translation of these vaccine approaches to humans has, so far, been limited to experimental passive applications. Periodontal disease is a destructive chronic inflammatory disease of the connective tissues and bone housing the teeth, having an infectious initiation of one or several associated bacterial species. Early studies in experimental animals indicated that active immunization with initiating microorganisms (most frequently Porphyromonas gingivalis) was protective with respect to periodontal bone resorption. Successful immunizations have targeted potential (P. gingivalis) virulence components, including whole cells, fimbriae/fimbrial subunit, hemagglutinin B, outer membrane protein, cysteine proteases, cysteine protease DNA, and therapeutic antibody to host receptor activator of NF-κB ligand (RANKL). Many studies have employed mucosal immunization by local immunization, intranasal administration, sublingual immunization, and parenteral administration. Mucosal IgA antibody induction studies seem to be most effective and least harmful by inducing SIgA antibody and also salivary IgG and blood and crevicular fluid IgG antibody. The multiple sources and isotypes of antibody generated when mucosal type immunity is elicited may be a most important requisite for antibody-mediated diminished periodontal bone resorption. T cell and B cell osteoclastogenic functions mediated by RANKL contribute to bone resorption and inflammation in experimental periodontal diseases Passive therapeutic immunization with antibody to RANKL or related protein compounds is effective at modulating experimental periodontal bone loss. Now there are two approaches to periodontal vaccine development: prophylactic and therapeutic.