Chronic periodontitis is a world wide public health problem effecting 5-20% of any population. Recent studies are now strongly indicating that chronic periodontitis effects systemic health and is a major risk factor for coronary heart disease, preterm and low birth weight babies, pancreatic cancer, diabetes and rheumatoid arthritis. Objective: of our research is to develop a vaccine directed to the major periodontal pathogen; Porphyromonas gingivalis. Method: Our initial research has focused on the major virulence factor for P. gingivalis the RgpA-Kgp proteinase-adhesin complex. We have produced recombinant proteins to each of the proteinases and adhesins as well as synthetic peptides representing repeated motifs form the RgpA-Kgp complex and evaluated these in the mouse periodontitis experimental model. Results: Using the periodontitis experimental model peptides representing sequences from the proteinase active site and a recombinant protein representing the KgpA1 adhesin were found to be the most effective vaccine candidates in providing protection against P. gingivalis induced bone loss. These individual vaccine antigens were found to be as effective as the native RgpA-Kgp complex. Analysis of the protective immune response found that a Th2 cytokine and antibody response was associated with protection. In an attempt to improve vaccine efficacy we have produced a recombinant chimeric protein of the proteinase active site sequence and KgpA1. This chimera was found to provide significant (p<0.01) more effective protection against P. gingivalis induced bone loss than the native RgpA-Kgp complex or formalin killed P. gingivalis whole cells, in the periodontitis experimental models. Furthermore antibodies induced by the chimera were found to opsonise all P. gingivalis serotypes and all of the P. gingivalis clinical isolates tested. Conclusion: we have identified and produced a highly effective P. gingivalis vaccine candidate by combining peptide and recombinant protein vaccine approaches and shown that it is able to protect when administered prophylatically.
Division: Australian/New Zealand Division Meeting
Meeting:2011 Australian/New Zealand Division Meeting (Melbourne, Australia) Location: Melbourne, Australia
Year: 2011 Final Presentation ID: Abstract Category|Abstract Category(s):Scientific Groups
Authors
O'brien-simpson, Neil M.
( University of Melbourne, Carlton, N/A, Australia
)
Walsh, Katrina A.
( University of Melbourne, Carlton, N/A, Australia
)
Holden, James
( University of Melbourne, Carlton, N/A, Australia
)
Becher, Dorit
( CSL, Melbourne, N/A, Australia
)
Slakeski, Nada
( University of Melbourne, Carlton, N/A, Australia
)
Cross, Keith
( University of Melbourne, Carlton, N/A, Australia
)
Reynolds, Eric C.
( University of Melbourne, Carlton, N/A, Australia
)