Macaca fascicularis as a model in which to assess the safety and efficacy of a vaccine for periodontitis

Abstract

We have assessed Macaca fascicularis as a potential model in which to test the efficacy and safety of a vaccine for periodontitis. Twenty-eight animals were surveyed and 20 studied in more detail. Clinical periodontal status was assessed, the subgingival microflora analyzed especially for the presence and proportions of Porphyromonas gingivalis and titers and avidities of serum antibodies reactive with P. gingivalis measured. Probing depths ranged from 0.90 mm to 3.80 mm, Gingival Index scores from 0.00 to 4.00 and Plaque Index scores from 0.00 to 3.00. About 40% of sites bled on probing. The animals manifested a subgingival flora characteristic of the anaerobic gram-negative bacteria found in human periodontal pockets, including Actinobacillus actinomycetemcomitans, P. gingivalis, Bacteroides forsythus, Campylobacter rectus, Prevotella intermedia and Fusobacterium nucleatum. P. gingivalis was detected in 70 of 80 samples studied, ranging from 0.01% to 20% of the total flora. Serum antibody reactive with antigens of P. gingivalis was observed in all animals, with titers ranging from 1.0 enzyme-linked immunosorbent assay (ELISA) unit to 25 ELISA units and avidities from 0.10 M to 2.20 M. Antibody titer and maximum percentage of P. gingivalis were inversely correlated, indicating that a humoral immune response may be effective in reducing P. gingivalis overgrowth. M. fascicularis appears to be an excellent model for use in vaccine development.

Mucosal Vaccines for Dental Diseases

“…This evidence led to further experimental use of vaccines to affect PD in the same animal model using a vaccine containing formalinized P. gingivalis (monkey strain) as antigen. Persson et al (1994) demonstrated a significant reduction in alveolar bone loss and significantly lower proportions of P. gingivalis in the subgingival flora of vaccinated animals having high levels of opsonic anti-P. gingivalis antibody. These observations suggested that a mechanism of immune protection may be enhanced opsonization, phagocytosis, and killing of P. gingivalis or other relevant organisms.…”

“…Parenteral immunization Enhanced bone loss in all immunized Ebersole et al (1991) Whole cells from P. gingivalis Parenteral immunization Reduced P. gingivalis, less bone loss Persson et al (1994) Passive monoclonal anti-P. gingivalis in humans…”

“…With use of the model above and a protocol almost identical to that of Persson et al (1994), another study was conducted using cysteine protease (RgpA/Kgp, porphypain) and adjuvant from P. gingivalis (Page, 2004). Five young adult monkeys were immunized over 16 weeks, and five controls received adjuvant only.…”

“…However, immunization with P. gingivalis and B. fragilis resulted in a significant overgrowth of A. actinomycetemcomitans at ligated sites and enhanced PBR relative to the sham-immunized controls. Persson et al (1994) asked two questions: (1) Can immunization clear P. gingivalis from the subgingival flora?…”

The Role of Immunostimulants in Immunotherapy and Immunoprophylaxis

“…They are products from natural or synthetic origin with different chemical characteristic and mechanism of action (1,9,13,14,16,17,18,19,23).…”