Bacteria and the pathogenesis of periodontal diseases: vaccine development

Abstract

Periodontitis is a chronic inflammatory disease of the supporting tissues of the teeth leading to tissue destruction and tooth loss. Advances in the techniques used to identify microbial pathogens linked with periodontal tissue destruction, particularly in prospective clinical studies, have led to the identification of <i>Porphyromonas gingivalis</i> as a major aetiological agent in disease initiation and progression. Detailed molecular studies of the pathogen have shown that extracellular proteinases are a key virulence factor for this bacterium. The proteinases are expressed and secreted by a novel secretion system as polyproteins with C-terminal adhesins. Once secreted the polyproteins are attached to a novel surface LPS anchor and proteolytically processed to form a non-covalent complex of proteinases and adhesins. This surface complex can be released into the host tissue where it dysregulates the host immune response and induces vascular disruption and tissue destruction. The purified proteinase-adhesin complex protects against disease when used as a vaccine in animal models of period-ontitis. Novel recombinant chimeric forms of the proteinase and adhesins when used as a vaccine in animals produced antibodies to both the proteinase active site and major adhesin and provided better protection against periodontal tissue destruction than the native complex or killed whole cells. This chimeric vaccine shows potential for the development of a vaccine against human disease.