CORE--PRECLINICAL TRIALS AND PATHOLOGY

该核心的总体目标(核心A：临床前试验和 病理学)是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 在本申请的项目1-4中提出。这将包括拨备 2-3岁无逆转录病毒(SIV，STLV-1，SRV)的恒河猴 耶尔基斯猕猴繁殖群体；用DNA免疫动物 或项目1和2中详细说明的蛋白质免疫原；静脉注射病毒 精选免疫动物的挑战；日常监测 实验动物；定期体检、采血 以及实验动物的淋巴组织活检来评估 动物的临床和身体状况，并为 实验室评价(项目1-4)；CBCs的性能和流量 测定淋巴细胞亚群的细胞学评价；RT-QC-PCR 免疫受试者血浆病毒载量的测定 动物.经免疫和挑战的动物的PBMC的病毒培养 确定疫苗在预防感染方面是否有效； 原位杂交和/或免疫组织化学研究的性能 通过活组织检查或在免疫、挑战的身体解剖中收集的样本 动物；以及完整的大体和组织学评估的表现 在所有实验动物中，死亡的或在 学习的过程。 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 建议的评估将允许通过以下方式评估疫苗效力 关于预防感染(消毒免疫)或 修改挑战后病毒载量或病毒设定值。

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.