Cell envelope and cell wall immunization of Macaca fascicularis: effect on the progression of ligature-induced periodontitis.

The nonhuman primate, Macaca fascicularis, was used to study the role of immunization with selected members of the periodontopathic microbiota in the longitudinal progression of ligature-induced periodontitis. Animals were immunized with cell envelope antigens prepared from Porphyromonas gingivalis and Prevotella intermedia, and a mixture prepared from Fusobacterium nucleatum, Campylobacter rectus, and Actinomyces viscosus. Serum immunoglobulin G (IgG), IgM and IgA isotype antibodies increased significantly in all immunization groups and were specific for each of the immunogens. P. gingivalis and P. intermedia immunization resulted in a stabilization of the proportions of these species throughout most of the experiment. The high P. gingivalis antibody titer resulted in low P. gingivalis numbers being recovered. P. gingivalis immunization, while lowering recoverable viable P. gingivalis, resulted in significantly increased levels of Prevotella loescheii, Prevotella buccae, Bacteroides macacae and Prevotella melaninogenica compared with preligation and preimmunization levels. Actinobacillus actinomycetemcomitans, Capnocytophaga spp. and Eikenella spp. remained at preligation levels postimmunization. Campylobacter spp. increased significantly during the course of the experiment in all groups, whereas the levels of Fusobacterium spp. decreased. Plaque indices and bleeding on probing showed significant increases in all groups following ligation, with the placebo group showing the greatest increase. Pocket depth measurements revealed that , whereas the placebo animals showed an approximate 5% increase, the P. gingivalis- and P. intermedia-immunized groups showed nearly a 20% increase in pocket depth. Attachment level measurements showed significantly greater attachment loss in the P. gingivalis- and P. intermedia-immunized groups, and the F. nucleatum + C. rectus + A. viscosus immunization appeared to prevent significant changes in pocket depth/attachment level loss. Radiographic measurement of bone loss by computer-assisted densitometric image analysis revealed that the placebo group lost bone throughout the experiment. P. gingivalis- and P. intermedia-immunized groups showed an exacerbated loss of bone density and the group immunized with F. nucleatum + C. rectus + A. viscosus exhibited significantly lower amounts of bone loss when analyzed by computer-assisted densitometric image analysis, compared with the other immunized groups. Although immunization with P. gingivalis and P. intermedia cell envelope antigens had an effect on their emergence in the complex microbiota of the developing periodontal pocket, this immunization also resulted in greater bone loss than immunization with F. nucleatum + C. rectus + A. viscosus, suggesting that, whereas selective members of the putative periodontopathic microbiota may play a direct role in periodontal tissue destruction, the complexity of the subgingival microbiota dictates that considerable scrutiny is required to select useful immunogens that can elicit functional protection from periodontal tissue destruction induced by oral microorganisms that already colonize or infect the host.