CORE--PRECLINICAL TRIALS AND PATHOLOGY

本核心的总体目标（核心A：临床前试验和 病理学）提供所需的实验动物和支持 促进艾滋病疫苗开发研究所需的服务 本申请中的项目1-4中提出的。这将包括提供 2-3岁无逆转录病毒（SIV，STLV-1，SRV）恒河猴， 耶基斯猕猴繁殖群;用DNA免疫动物 或项目1和2中详述的蛋白免疫原;静脉内病毒 选定免疫动物的攻毒;每日监测 实验动物;定期体检、采血 和淋巴结活组织检查，以评估 动物的临床和身体状况，并提供标本， 实验室评估（项目1-4）; CBCs的性能和流量 测定淋巴细胞亚群的细胞计数评价 测定以评价免疫攻毒受试者血浆中的病毒载量 动物;免疫、攻毒动物PBMC的病毒培养物， 确定疫苗是否有效预防感染; 进行原位杂交和/或免疫组织化学研究 通过活检或尸检采集的免疫、攻毒 动物;以及进行完整的大体和组织学评价 所有在实验期间死亡或被处死的实验动物 研究的过程。 提供这些资源和支助服务将有助于 项目1-4所述的艾滋病疫苗的开发和测试， 这个应用程序。病毒学、免疫学和临床病理学 拟议的评价将允许评估疫苗的效力， 关于预防感染（杀菌免疫）或 改变攻毒后病毒载量或病毒设定点。

The overall objective for this core (Core A: Pre-clinical Trials and Pathology) are to provide the required experimental animals and support services needed to facilitate the AIDS vaccine development studies proposed in Projects 1-4 in this application. This will include provision of 2-3 year old retrovirus-free (SIV, STLV-1, SRV) rhesus macaques from the Yerkes macaque breeding colonies; immunization of the animals with DNA or protein immunogens as detailed in Projects 1 and 2; intravenous viral challenges of selected immunized animals; daily monitoring of the experimental animals; periodic physical examinations, blood collections and lymph node biopsies from the experimental animals to assess the animals' clinical and physical condition and to provide specimens for laboratory evaluations (Projects 1-4); performance of CBCs and flow cytometry evaluations to determine lymphocyte subsets; RT-QC-PCR determination to evaluate viral load in the plasma of immunized challenged animals; viral cultures of PBMCs of immunized, challenged animals to determine if the vaccines were effective in preventing infection; performance of in situ hybridization and/or immunohistochemistry studies of specimens collected by biopsy or at necropsy of immunized, challenged animals; and the performance of complete gross and histologic evaluation of all experimental animals that die or that are sacrificed during the course of the study. Provision of these resources and support services will facilitate the development and testing of AIDS vaccines as described in Projects 1-4 of this application. The virological, immunologic and clinico-pathologic evaluations proposed will allow an assessment of vaccine efficacy with respect to either the prevention of infection (sterilizing immunity) or modification of post-challenge virus load or viral set point.