Oral Immunization with RecombinantStreptococcus gordoniiExpressingPorphyromonas gingivalisFimA Domains

Abstract

Porphyromonas gingivalis, a gram-negative anaerobe, is implicated in the etiology of adult periodontitis. P. gingivalis fimbriae are one of several critical surface virulence factors involved in both bacterial adherence and inflammation. P. gingivalis fimbrillin (FimA), the major subunit protein of fimbriae, is considered an important antigen for vaccine development against P. gingivalis-associated periodontitis. We have previously shown that biologically active domains of P. gingivalis fimbrillin can be expressed on the surface of the human commensal bacterium Streptococcus gordonii. In this study, we examined the effects of oral coimmunization of germfree rats with two S. gordonii recombinants expressing N (residues 55 to 145)-and C (residues 226 to 337)-terminal epitopes of P. gingivalis FimA to elicit FimA-specific immune responses. The effectiveness of immunization in protecting against alveolar bone loss following P. gingivalis infection was also evaluated. The results of this study show that the oral delivery of P. gingivalis FimA epitopes via S. gordonii vectors resulted in the induction of FimA-specific serum (immunoglobulin G [IgG] and IgA) and salivary (IgA) antibody responses and that the immune responses were protective against subsequent P. gingivalis-induced alveolar bone loss. These results support the potential usefulness of the S. gordonii vectors expressing P. gingivalis fimbrillin as a mucosal vaccine against adult periodontitis.

The Biofilm Concept: Consequences for Future Prophylaxis of Oral Diseases?

“…As vehicles for passive immunization, both milk from immunized cows (Shimazaki et al, 2001) and transgenic plants (Ma et al, 1998) have been tested, with encouraging results. Likewise, chimeric recombinant microbial vectors that are avirulent but which express antigens from S. mutans (Huang et al, 2001;Taubman et al, 2001) or P. gingivalis (Sharma et al, 2001) have been shown to provide protection against dental caries and alveolar bone loss, respectively, in experimental animals. However, no vaccination scheme in humans is yet clinically applicable.…”

Immunization with the RgpA-Kgp Proteinase-Adhesin Complexes ofPorphyromonas gingivalisProtects against Periodontal Bone Loss in the Rat Periodontitis Model

“…Other investigators have demonstrated some protection against periodontal bone loss in the rat periodontitis model upon immunization with a purified or recombinant P. gingivalis fimbrial protein or with a commensal bacterium expressing biologically active domains of the fimbrial protein (11,41). In a recent study by Sharma et al (41) oral immunization of rats with Streptococcus gordonii expressing domains of the P. gingivalis fimbrial protein (FimA) induced FimA-specific serum (IgG and IgA) and salivary (IgA) antibodies.…”

“…In a recent study by Sharma et al (41) oral immunization of rats with Streptococcus gordonii expressing domains of the P. gingivalis fimbrial protein (FimA) induced FimA-specific serum (IgG and IgA) and salivary (IgA) antibodies. The immunization resulted in partial (60%) protection against P. gingivalisinduced periodontal bone loss.…”

Immunization withPorphyromonas gingivalisCapsular Polysaccharide PreventsP. gingivalis-Elicited Oral Bone Loss in a Murine Model

“…Despite this, there are no vaccines in use for the prevention of adult periodontitis. Because P. gingivalis is a significant periodontal pathogen, investigators have assessed the potential of several P. gingivalis antigens to function as vaccine candidates, including killed whole P. gingivalis organisms and specific P. gingivalis antigens such as fimbriae, fimbrillin peptides, gingipains, hemagglutinins, and others (7,9,11,13,22,29,31). A conjugate vaccine consisting of P. gingivalis CPS and P. gingivalis fimbriae was shown to prevent P. gingivalis infection when a murine subcutaneous challenge model was used (6).…”