Effects of immunization with Porphyromonas gingivalis and Prevotella intermedia on progression of ligature-induced periodontitis in the nonhuman primate Macaca fascicularis

Abstract

The nonhuman primate (Nhp) has proven to be a useful model of human periodontitis. This study describes the immunological characteristics of this model and the ability of active immunization to interfere with ecological changes in the microbiota and its associated disease symptoms. Nhps were parenterally immunized with whole-cell antigens of Porphyromonas gingivalis and Prevotella intermedia. The immunization elicited an approximate 2-log increase in serum immunoglobulin G (IgG), IgM, and IgA isotype antibody that was highly specific for these immunogens. Postimmunization and postligation, there was minimal change in the levels of specific antibody. P. gingivalis immunization significantly inhibited the emergence of this species during disease progression. In contrast, induction of anti-P. intermedia antibody had a minimal effect on this species within the subgingival plaque. Plaque indices showed few changes that could be attributed to active immunization. Both bleeding on probing and loss of attachment were higher in ligated sites of immunized animals than in the placebo-treated group. A signfficant increase in bone density loss was observed in the ligated teeth from immunized versus control animals. These findings indicate that active immunization of Nhps can elicit a substantial systemic immune response; however, while this response may effect the emergence of an individual microorganism, it appears that other ecological considerations are critical in disease progression. It is also possible that the induction of a broad-based immune response to multiple bacterial antigens can result in increased disease, potentially associated with hypersensitivity reactions to the bacteria in the subgingival plaque.

The effect of immunization on the response to P. gingivalis infection in mice is adjuvant‐dependent

“…For example, Persson et al (1994) showed that vaccination with P. gingivalis provided protection against experimentally induced periodontitis in the monkey model. In contrast, Ebersole et al (1991) could not demonstrate any protection against experimental periodontitis, using P. gingivalis vaccine in the same model. However, no study has raised the possibility, or tested the hypothesis, that these differences are because of the use of different adjuvants in the vaccine.…”

“…Studies on the development of a vaccine to prevent periodontal disease by immunization with antigens from Porphyromonas gingivalis have produced variable and conflicting results (Page 2000). Several studies using both mice and primates have demonstrated that immunization with P. gingivalis results in protection against experimentally induced periodontal destruction (Okuda et al 1988, Persson et al 1994, Genco et al 1998, Gonzalez et al 2003, while other animal studies have been unable to demonstrate protection (Ebersole et al 1991, Moritz et al 1998). In humans, numerous studies have demonstrated that patients with periodontitis mount a humoral immune response to plaque bacteria during the course of their disease (Tew et al 1985, Mooney et al 1997, and antibody titres to P. gingivalis have been shown to be inversely related to disease severity (Okuda et al 1988, Mooney et al 1997).…”

Inhibition of osteoclastogenesis by opsonizedPorphyromonas gingivalis

“…[43][44][45][46] As we have shown previously, nonhuman primates can be vaccinated with Pg or selected components resulting in significant increases in local and systemic IgG antibodies leading to decreased clinical disease in a ligature-induced model. 19,27,28 As such, numerous studies in rodent, canine, and nonhuman primate models support the finding that active vaccination with Pg or its component parts can significantly decrease induced periodontitis. [45][46][47][48][49] Our findings suggest that the elevated antibodies in humans that occur in response to naturally occurring periodontitis can help to ameliorate this process, potentially through opsonization of oral bacteria, which suppress the osteoclast-mediated bone loss in periodontitis.…”

“…Bacteria were fixed in 0.5% buffered formal saline by incubation at RT overnight. 19 Once the cells have been fixed, they were washed extensively in PBS-EDTA and stored at 4°C in a concentrated form. Heat-killed Pg were prepared following incubation of cultures at 70°C in water bath for 1 hour, pelleted and stored in PBS at 4°C until usage.…”

“…Vaccination against Pg has been shown to elevate systemic IgG antibody levels and decrease PD, but little is known how the antibodies actually abrogate this disease process. 19,27,28 We hypothesized that antibodies to Pg interfere with the inflammatory nature of the pathogen and inhibit OC formation. Toward this end, pooled human sera with specific antibody titer to Pg obtained previously [29][30][31] were used to assay the effects on OC differentiation and function.…”