IMMUNIZATION OF MACACA FASCICULARIS

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The purposes of this study are to confirm the hypothesis that immunization of Macaca fascicularis with a vaccine containing killed Porphyromonas gingivalis with SAF-M adjuvant can induce protection against experimental periodontitis; to monitor changes in the subgingival flora and to measure antibodies specific for antigens of P. gingivalis in serum, gingival crevicular fluid (GCF), and saliva; and measure marker cytokines and prostaglandins in GCF during immunization and induction of experimental periodontitis. Animals will be surveyed with regard to general and oral health conditions, composition of the subgingival flora, and titers of serum antibodies specific for antigens of P. gingivalis. Using specified inclusion and exclusion criteria, 14 animals will be enrolled in a group to be immunized, and 14 into a group to receive placebo vaccine. Animals will be vaccinated at baseline and weeks 3, 6, and 16, and at week l6 the mandibular posterior teeth ligated. At designated timepoints throughout the study, we will measure inflammation, bleeding, plaque, pocket depth, and attachment level; and take standardized radiographs of test teeth for measurement of alveolar bone by subtraction radiography. At the same timepoints, we will harvest blood, GCF, saliva, and subgingival flora from test teeth. Presence and amounts of P. gingivalis and five other putative periodontal pathogens will be measured in the flora. Antibodies specific for antigens of P. gingivalis in serum, saliva, and GCF will be measured by ELISA and avidity of serum antibodies determined. Presence and amounts of IL- 1beta, TNF-alpha, PGE2, and TxB2 in GCF will be assessed. At week 32, ligatures will be removed from one randomly selected side of the mouth and approximately 10/7 viable P. gingivalis applied to test teeth, and the application repeated at week 36. Data entry and management will be performed by the Data Manager under the supervision of the Biostatistician and the Investigators. Descriptive and analytic statistics will e used including repeated measures ANOVA to evaluate within- and between-animal variability due to study factors. Data through week 32 will be pooled with that of the previous study to increase the power of statistical tests to confirm that immunization can suppress alveolar bone loss and affect the flora. Completion of this stud will confirm that immunization confers protection, as well as greatly extend our knowledge of the effects of systemic, local, and mucosal immune responses on the subgingival flora, and the mechanisms through which specific antibodies attenuate bone destruction.