Abstract
Periodontal diseases are chronic inflammatory diseases of the periodontium that result in progressive destruction of the soft and hard tissues supporting the teeth, and it is the most common cause of tooth loss among adults. In the US alone, over 100 million individuals are estimated to have periodontal disease. Subgingival bacteria initiate and sustain inflammation, and, although several bacteria have been associated with periodontitis, Porphyromonas gingivalis has emerged as the key etiological organism significantly contributing to the disease. Currently, intensive clinical maintenance strategies are deployed to mitigate the further progression of disease in afflicted individuals; however, these treatments often fail to stop disease progression, and, as such, the development of an effective vaccine for periodontal disease is highly desirable. We generated a conjugate vaccine, comprising of the purified capsular polysaccharide of P. gingivalis conjugated to eCRM®, a proprietary and enhanced version of the CRM197 carrier protein with predetermined conjugation sites (Pg-CV). Mice immunized with alum adjuvanted Pg-CV developed robust serum levels of whole organism-specific IgG in comparison to animals immunized with unconjugated capsular polysaccharide alone. Using the murine oral bone loss model, we observed that mice immunized with the capsule-conjugate vaccine were significantly protected from the effects of P. gingivalis-elicited oral bone loss. Employing a preclinical model of infection-elicited oral bone loss, our data support that a conjugate vaccine incorporating capsular polysaccharide antigen is effective in reducing the main clinical endpoint of periodontal disease—oral bone destruction. Further development of a P. gingivalis capsule-based conjugate vaccine for preventing periodontal diseases is supported.
Highlights
Periodontal disease is a chronic oral inflammatory disease that is initiated by a changed subgingival microflora, which leads to the progressive destruction of the soft and hard tissues supporting the teeth and, in severe disease, is the number one cause of tooth loss in adults [1]
Our group and others have focused on P. gingivalis capsular polysaccharide (CPS) as a vaccine, and we have found that mice immunized with this molecule in the purified form are protected from subsequent live organism-elicited oral bone loss [20, 29]
Molecular weight analysis, using size exclusion chromatography, coupled to light scattering with refractive index and ultraviolet detection, resulted in the ability to monitor the various stages of the vaccine production process, stating with the native full-length CPS, to the mechanically sized polysaccharide, and, the ultimate polysaccharide protein conjugate
Summary
Periodontal disease is a chronic oral inflammatory disease that is initiated by a changed subgingival microflora, which leads to the progressive destruction of the soft and hard tissues supporting the teeth and, in severe disease, is the number one cause of tooth loss in adults [1]. In the US, it is estimated that ∼42% of the adult population have periodontal disease, making this disease one of the most common chronic infectious diseases affecting humans [2]. Periodontitis is prevalent in adults, it can affect children and adolescents, and is widespread among elderly populations. The etiology of periodontal disease is polymicrobial, Porphyromonas gingivalis is among the more commonly encountered organisms known to become overpopulated during the transition to disease [8] and, is identified as key bacteria associated with this disease
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