Vaccination and periodontitis: myth or reality.
In most industrialised countries approximately 15% of the population has enhanced risk for moderate to severe periodontitis. The disease is caused by infection by gram-negative, anaerobic bacteria including Porphyromonas gingivalis and Bacteroides forsythus. There is evidence that P. gingivalis is a key pathogen. Using ligature-induced periodontitis in the non-human primate Macaca fascicularis as a model, we immunised 10 animals using intact killed P. gingivalis and SAF-M adjuvant and 10 controls using adjuvant only. The vaccine, containing 250 microg protein/ml, was injected subcutaneously in the neck and into the deltoid muscle (0.5 ml each site) at baseline and weeks 3, 6, and 16, and the mandibular posterior teeth ligated at week 16. At weeks 30 and 36 changes in alveolar bone, measured using digital subtraction radiography, were used as the outcome measure. Even though periodontitis in humans and in this animal model is a polymicrobial disease, immunisation with a vaccine containing a single bacterial species, P. gingivalis, induced protection. Of all the P. gingivalis components that have been studied, the cysteine proteases have the greatest potential as vaccine antigens. In a pilot study using the same protocol, we have shown that porphypain-2 purified from P. gingivalis is effective in inducing protection. Although opsonisation and bacterial cell killing may be involved in protection, other mechanisms such as antibody mediated reduction of levels of inflammatory mediators such as PGE2 and neutralisation of virulence factors may be important. In neither the whole cell vaccine nor the purified cysteine protease vaccine studies were signs of toxicity observed. In light of the increasing evidence that periodontitis significantly increases risk for potentially fatal diseases such as coronary heart disease, stroke and complications from diabetes mellitus a successful vaccine for periodontitis could have health benefits far exceeding the prevention of periodontitis.
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Department of Periodontics and the Regional Clinical Dental Research Center, School of Dentistry, and the Department of Pathology, School of Medicine, University of Washington, Seattle 98195, USA.
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000517:prevention & control; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000276:immunology / Q000627:therapeutic use; D001428:Bacterial Vaccines / Q000008:administration & dosage; D016866:Bacteroidaceae Infections / Q000517:prevention & control; D001442:Bacteroides Infections / Q000517:prevention & control; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000627:therapeutic use; D015232:Dinoprostone / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008252:Macaca fascicularis; D009229:Mythology; D010518:Periodontitis / Q000517:prevention & control*; D010865:Pilot Projects; D016966:Porphyromonas gingivalis / Q000276:immunology*; D011856:Radiographic Image Enhancement; D013382:Subtraction Technique; D016896:Treatment Outcome; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000008:administration & dosage; D037521:Virulence Factors / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D018836:Inflammation Mediators; D015164:Vaccines, Inactivated; D037521:Virulence Factors; D003546:Cysteine Endopeptidases; C099479:porphypain protein, Porphyromonas gingivalis; D015232:Dinoprostone