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    An immune response directed to proteinase and adhesin functional epitopes protects against Porphyromonas gingivalis-induced periodontal bone loss

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    Author
    O'Brien-Simpson, NM; Pathirana, RD; Paolini, RA; Chen, YY; Veith, PD; Tam, V; Ally, N; Pike, RN; Reynolds, EC
    Date
    2005-09-15
    Source Title
    JOURNAL OF IMMUNOLOGY
    Publisher
    AMER ASSOC IMMUNOLOGISTS
    University of Melbourne Author/s
    O'Brien-Simpson, Neil; Paolini, Rita; Chen, Yu-Yen; Veith, Paul; Reynolds, Eric; PATHIRANA, RISHI DELAN; TAM, VIVIAN
    Affiliation
    Dental Science
    Metadata
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    Document Type
    Journal Article
    Citations
    O'Brien-Simpson, N. M., Pathirana, R. D., Paolini, R. A., Chen, Y. Y., Veith, P. D., Tam, V., Ally, N., Pike, R. N. & Reynolds, E. C. (2005). An immune response directed to proteinase and adhesin functional epitopes protects against Porphyromonas gingivalis-induced periodontal bone loss. JOURNAL OF IMMUNOLOGY, 175 (6), pp.3980-3989. https://doi.org/10.4049/jimmunol.175.6.3980.
    Access Status
    This item is currently not available from this repository
    URI
    http://hdl.handle.net/11343/26556
    DOI
    10.4049/jimmunol.175.6.3980
    Description

    C1 - Journal Articles Refereed

    Abstract
    Porphyromonas gingivalis, a pathogen associated with periodontitis, bound to fibrinogen, fibronectin, hemoglobin, and collagen type V with a similar profile to that of its major virulence factor, the cell surface RgpA-Kgp proteinase-adhesin complex. Using peptide-specific, purified Abs in competitive inhibition ELISAs and epitope mapping assays, we have identified potential adhesin binding motifs (ABMs) of the RgpA-Kgp complex responsible for binding to host proteins. The RgpA-Kgp complex and synthetic ABM and proteinase active site peptides conjugated to diphtheria toxoid, when used as vaccines, protected against P. gingivalis-induced periodontal bone loss in the murine periodontitis model. The most efficacious peptide and protein vaccines were found to induce a high-titer IgG1 Ab response. Furthermore, mice protected in the lesion and periodontitis models had a predominant P. gingivalis-specific IL-4 response, whereas mice with disease had a predominant IFN-gamma response. The peptide-specific Abs directed to the ABM2 sequence (EGLATATTFEEDGVA) protected against periodontal bone loss and inhibited binding of the RgpA-Kgp complex to fibrinogen, fibronectin, and collagen type V. Furthermore, the peptide-specific Abs directed to the ABM3 sequence (GTPNPNPNPNPNPNPGT) protected against periodontal bone loss and inhibited binding to hemoglobin. However, the most protective Abs were those directed to the active sites of the RgpA and Kgp proteinases. The results suggest that when the RgpA-Kgp complex, or functional binding motif or active site peptides are used as a vaccine, they induce a Th2 response that blocks function of the RgpA-Kgp complex and protects against periodontal bone loss.
    Keywords
    Analytical Biochemistry; Bacteriology ; Dentistry not elsewhere classified ; Prevention - Biologicals (e.g. Vaccines); Dental Health

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