CORE--PRECLINICAL PRIMATE MODELS

该核心的目标是实现标准化协议， 测试候选疫苗抗原的免疫原性和安全性， 人类灵长类动物 具体目标是确定最佳剂量， 获得有效和持久的给药途径 确定配子抗体的血清和生殖道滴度 灵长类动物模型中的抗原。 将特别注意 测量和比较对特定配子的免疫应答 猕猴输卵管液、宫颈粘液和血清中抗原的研究 束状的是，避孕发展所选择的物种 分支为研究重点。 这一核心的具体职能是：1）确保健康和 免疫学和生殖研究中灵长类动物的福利; 2） 用重组蛋白和肽免疫原刺激猴; 3)采集灵长类动物血清、输卵管液和宫颈粘液 受试者; 4）确定抗体的数量， 随着时间的推移，每只动物中的特异性免疫原; 5）定量 每种体液中产生的针对特定配子抗原的抗体类别 使用猴子特异性试剂; 6）通过以下方式优化免疫反应： 改变抗原递送的剂量、制剂、途径和时间; 7）确定特异性免疫原的安全性。 从核心项目D获得的信息对于准备大型 计划进行的大规模避孕效果试验 主要是在加州地区灵长类动物研究中心（CRPRC）， 戴维斯，一旦免疫原性和安全性评价已经完成， 在这个核心中完成。 然而，预计一些功效 测试可以在弗吉尼亚州的核心D中进行。这种灵活性是 要求尽量减少由于可用性而可能出现的延误， 猴子和笼子里。 两者之间的合作 中心一直在进行信息交流，猴子， 猴子的组织是有益的 核心D产生的数据 CRPRC将帮助确定哪些抗原适合 人体临床试验的候选人。 有鉴于此，研究将 重点是确定最小剂量， 维持免疫反应。

The objective of this core is to implement standardized protocols to test candidate vaccine antigens for immunogenicity and safety in non- human primates. Specific goals are to determine the optimal dose and route of administration required to obtain effective and persistent serum and reproductive tract titers of antibody of defined gamete antigens in the primate model. Particular attention will be paid to measuring and comparing the immune response to defined gamete antigens in oviductal fluids, cervical mucus and serum in Macaca fascicular is, the species chosen by the Contraception Development Branch for research focus. Specific functions of this core are: 1) to ensure the health and welfare of primates for immunologic and reproductive studies; 2) to inoculate monkeys with recombinant proteins and peptide immunogens; 3) to collect serum, oviductal fluid and cervical mucus from primate subjects; 4) to determine the quantity of antibody developed to specific immunogens in each animal over time; 5) to quantitiate the classes of antibodies arising to defined gamete antigens in each fluid using monkey-specific reagents; 6) to optimize immune responses by varying doses, formulations, routes and timing of antigen delivery; and 7) to determine the safety of specific immunogens. Information obtained from Core D is essential to prepare for large- scale contraceptive efficacy trials which are planned to be conducted mainly at the California Regional Primate Research Center (CRPRC) in Davis, once immunogenicity and safety evaluations have been completed in this core. However, it is anticipated that some efficacy tests may be performed in Core D at Virginia. This flexibility is required to minimize delays that may arise due to availability of monkeys and cages at each facility. Collaboration between the two Centers has been ongoing and exchange of information, monkeys, and monkey tissue has been beneficial. The data generated by the Core D and the CRPRC will help determine which antigens are suitable candidates for human clinical trials. In view of this, studies will focus on identifying the minimal dose which will optimize and and sustain immune responses.