Immunization With Porphyromonas gingivalis Cysteine Protease: Effects on Experimental Gingivitis and Ligature‐Induced Periodontitis in Macaca fascicularis

Abstract

Targeting bacterial virulence factors such as proteases for immunization may hold the key to hmiting or preventing loss of attachment and alveolar bone in periodontal disease. This study examined the chnical, microbiological, and immunological responses following active immunization with a purified Porphyromonas gingivalis cysteine protease (porphypain‐2) in the nonhuman primate (Nhp) Macaca fascicularis. One group of Nhp was immunized with porphypain‐2 antigen while control Nhp received placebo injections. AU Nhp were subjected to experimental gingivitis followed by hgature‐induced periodontitis in a split‐mouth design. An enzyme‐hnked immunosorbent assay demonstrated that immunization elicited a significantly elevated and specific IgG antibody response to both whole cell P. gingivalis (36‐fold) and to porphypain‐2 (194‐fold). Checkerboard hybridization DNA analysis of subgingival plaque from ligated sextants demonstrated that 25% more Gram‐negative anaerobic species became significantly elevated from basehne and at earlier timepoints in the control group than in the immunized group. Immunization with this protease did not suppress the emergence of P. gingivalis. Chnical indices showed few changes related to immunization. Alveolar bone density changes demonstrated a highly significant loss in ligated sextants compared to non‐ligated sextants within the control group (P < 0.001), and a smaller but significant difference within the immunized group (P = 0.043). Comparison of ligated sextants only demonstrated more bone loss in the control group versus the immunized group (−13.07±9.51 versus −9.41±6.18; computerassisted densitometric image analysis units ± SD); the difference approached, but did not reach, significance. The results suggest that porphypain‐2 may contribute to the pathogenic potential of the subgingival plaque microbiota in the Nhp model of hgature‐induced periodontitis, and that active immunization with porphypain‐2 appeared capable of altering this pathogenic response. J Periodontol 1998;69:686–697.

Immunization withPorphyromonas gingivalisCapsular Polysaccharide PreventsP. gingivalis-Elicited Oral Bone Loss in a Murine Model

“…Interestingly, this antigen also elicited a potent IgG response, and the animals immunized with P. gingivalis CPS were protected from P. gingivalis-elicited oral bone loss. To date, several P. gingivalis vaccine candidates have been reported to prevent P. gingivaliselicited oral bone loss (8,9,13,18,19,22,28) while other P. gingivalis antigens, such as LPS, do not appear to provide protection from subsequent P. gingivalis infection (5). Unexpectedly, we observed that mice immunized with P. gingivalis CPS develop an IgG response that recognizes P. gingivalis whole organisms.…”

“…Despite this, there are no vaccines in use for the prevention of adult periodontitis. Because P. gingivalis is a significant periodontal pathogen, investigators have assessed the potential of several P. gingivalis antigens to function as vaccine candidates, including killed whole P. gingivalis organisms and specific P. gingivalis antigens such as fimbriae, fimbrillin peptides, gingipains, hemagglutinins, and others (7,9,11,13,22,29,31). A conjugate vaccine consisting of P. gingivalis CPS and P. gingivalis fimbriae was shown to prevent P. gingivalis infection when a murine subcutaneous challenge model was used (6).…”

Chronic periodontitis and rheumatoid arthritis – microbiological aspects

“…Immunisation with cysteine proteases, purified from P. gingivalis against CP, may be important to the prevention from RA and its treatment (24). P. gingivalis is associated with the citrullination process and might participate in the loss of self-tolerance after the development of RA.…”

Impact of Mucosal Inflammation on Oral Simian Immunodeficiency Virus Transmission

“…Clinical attachment level (CAL) values were calculated from the pocket depth and recession measures. A gingival bleeding score, following determination of the pocket depth measure, was obtained (21)(22)(23).…”

“…Genital coinfections, such as genital herpes, gonorrhea, syphilis, and chlamydia, as well as yeast and bacterial vaginal infections, or host responses to these pathogens, create an inflammatory environment that favors HIV-1 infection and dissemination (18). Periodontal disease in the form of gingivitis represents a form of mucosal inflammation that is found in a significant proportion of the world population (19,20), and there is a well-established and reproducible nonhuman primate model of ligature-induced gingivitis (21)(22)(23). The study described here addresses the question of whether the induction of a common moderate inflammatory state of the gingival mucosa impacts oral SIV transmission and the induction of immune modulators in the rhesus macaque model.…”