Periodontal diseases are bacterial-associated inflammatory diseases of the supporting tissues of the teeth and the more aggressive forms, periodontitis, are characterized by the destruction of the tooth supporting structures. Current treatments for the periodontal diseases are nonspecific and are based on the continued removal of subgingival plaque by mechanical means, often involving surgical procedures. This ongoing therapy is costly and has a variable prognosis due to patient non-compliance. Recent evidence has demonstrated that the bacterium Porphyromonas gingivalis is a major etiologic agent of some forms of these diseases. The broad objective of this application is to determine the suitability of the major outer membrane proteins of P. gingivalis, that the earlier studies by identified candidates for the development of a defined recombinant or synthetic vaccine. In the long-term, this may lead to the development of effective, specific and novel prophylactic and therapeutic strategies for P. gingivalis-associated periodontitis. Over thirty outer membrane proteins of P. gingivalis have been developed and six of these will make excellent candidates for vaccine development. Specifically, a preparation will be used to prepare these selected P. gingivalis outer membrane proteins and protein fragments using a bacterial expression system and determine the immune response to these purified recombinant proteins in mice. A further Aim is the preparation of synthetic peptide multivalent constructs based on immunogenic sequences of the outer membrane proteins. The recombinant proteins, protein fragments and synthetic peptide multivalent constructs will be tested as defined vaccines against P. gingivalis in murine models of disease.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Special Emphasis Panel (ZRG1-OBM-1 (02))
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Bhargava, Sangeeta
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University of Melbourne
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Pathirana, Rishi D; O'Brien-Simpson, Neil M; Visvanathan, Kumar et al. (2008) The role of the RgpA-Kgp proteinase-adhesin complexes in the adherence of Porphyromonas gingivalis to fibroblasts. Microbiology 154:2904-11
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Pathirana, Rishi D; O'Brien-Simpson, Neil M; Brammar, Gail C et al. (2007) Kgp and RgpB, but not RgpA, are important for Porphyromonas gingivalis virulence in the murine periodontitis model. Infect Immun 75:1436-42
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O'Brien-Simpson, Neil M; Pathirana, Rishi D; Paolini, Rita A et al. (2005) An immune response directed to proteinase and adhesin functional epitopes protects against Porphyromonas gingivalis-induced periodontal bone loss. J Immunol 175:3980-9