IMMUNIZATION OF MACACA FASCICULARIS

本研究的目的是证实这一假设， 用含有灭活疫苗免疫食蟹猴 SAF-M佐剂对牙龈卟啉单胞菌的保护作用 对实验性牙周炎;监测龈下的变化 植物群和测量牙龈卟啉单胞菌抗原特异性抗体 在血清、龈沟液（GCF）和唾液中;以及测量标记物 GCF中的细胞因子和胰头素在免疫和诱导期间 实验性牙周炎 将对动物进行调查， 一般和口腔健康状况，龈下植物群的组成， 和牙龈卟啉单胞菌抗原特异性血清抗体的滴度。 使用指定的入选和排除标准，将有14只动物 参加一个小组进行免疫接种，14人参加一个小组接受免疫接种， 安慰剂疫苗。 动物将在基线和第3、6、7、8周接种疫苗。 16周时结扎下颌后牙。 在 在整个研究的指定时间点，我们将测量炎症， 出血、斑块、囊袋深度和附着水平; 牙槽骨测量用标准化X线片 通过减影X线摄影。在同一时间点，我们将收获 血液、GCF、唾液和来自测试牙齿的龈下植物群。 存在和 牙龈卟啉单胞菌和其他五种假定的牙周病原体的量 将在植物群中测量。 特异性抗P. 将通过ELISA测量血清、唾液和GCF中的牙龈炎， 测定血清抗体的亲合力。 IL-1的存在和量 将评估GCF中的1 β、TNF-α、PGE 2和TxB 2。 在第32周， 将从嘴的随机选择一侧移除结扎线 和大约10/7的活牙龈卟啉单胞菌应用于测试牙齿，和 在第36周重复施用。 数据输入和管理将 由数据管理员在 生物统计学家和研究者。 描述和分析 将使用统计学（包括重复测量ANOVA）来评价 研究因素导致的动物内和动物间变异性。 数据 至第32周的数据将与先前研究的数据合并， 增加统计检验的效力，以证实免疫接种可以 抑制牙槽骨丢失并影响植物群。 完成本 研究将证实，免疫接种可提供保护， 极大地扩展了我们对系统性、局部性和 龈下植物群的粘膜免疫应答及其机制 特异性抗体通过其减弱骨破坏。

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.