Non-Human Primates

非人灵长类核心，核心B，将为所有临床前测试提供人员和化验 猪尾猕猴(Macaca Nomestrina)的候选疫苗。SLV抗原作为评价指标 免疫原将由Hahn博士和Compans博士开发，如项目1和2中所述， 将分别包括SlVmac239和SIVsm/Mac共识序列Env和Gag病毒样 颗粒以及DNA和重组腺病毒载体。新型佐剂，最初在小鼠中筛选 摩尔多瓦博士和Mestecky博士的项目4也将进行测试，以增强系统性和 粘膜免疫反应。每个实验方案将包括通过以下方式为猕猴接种疫苗 皮内和/或鼻腔接种免疫原，表征SLV特异性的体液和细胞 血液和粘膜分泌物中的免疫反应，通过静脉或 直肠内途径致病的Sly菌株，并评估保护水平。在.期间 免疫期间，将评估SIV特异性体液和细胞免疫反应 免疫球蛋白、免疫球蛋白A和中和抗体的产生及抗原特异性的增殖反应 淋巴细胞。一些血液样本将被送往莱特文博士的实验室(项目3)进行分析 淋巴细胞在代表整个gag基因的多肽库的反应中产生干扰素-g。 接种活病毒后，定期评估猕猴的病毒载量和体征 疾病，如皮疹、淋巴结病或体重减轻，将被做。这些检测将包括 病毒载量、抗体产生和各种血液学的定性和定量分析 参数，包括T细胞亚群和血小板的绝对数。杰夫·利夫森博士在NCI-Frederick癌症研究中心的实验室将通过QC-RT-PCR检测SIV病毒粒子RNA的血浆水平。该计划项目的总体目标是开发一种有效的艾滋病毒疫苗，以防止感染或疾病。为了确定最好的免疫原、佐剂和免疫路线，在SLV-猕猴模型中对疫苗策略进行初步测试是至关重要的，然后才能就选择用于第一阶段人体试验的候选艾滋病毒疫苗做出明智的决定。因此，非人类灵长类核心对于这个项目拨款的成功至关重要。

The Nonhuman Primate Core, Core B, will provide personnel and assays for all preclinical testing of candidate vaccines in pig-tailed macaques (Macaca nemestrina). SlV antigens for evaluation as immunogens will be developed by Drs. Hahn and Compans, as described in Projects 1 and 2, respectively, and will include SlVmac239 and SIVsm/mac consensus sequence Env and Gag virus-like particles as well as DNA and recombinant adenovirus vectors. Novel adjuvants, initially screened in mice by Drs. Moldoveanu and Mestecky, Project 4, also will be tested for enhancement of both systemic and mucosal immune responses. Each experimental protocol will consist of immunizing macaques by intradermal and/or intranasal inoculation of immunogens, characterizing SlV-specific humeral and cellular immune responses in blood and mucosal secretions, challenging macaques by either intravenous or intrarectal routes with a pathogenic SlY strain, and assessing the level of protection. During the immunization period, SIV-specific humoral and cellular immune responses will be evaluated for production of lgG, IgA, and neutralizing antibodies and for antigen-specific proliferative responses of lymphocytes. Some blood samples will be sent to Dr. Letvin's laboratory (Project 3) for analysis of interferon-g production by lymphocytes in response to peptide pools representing the entire gag gene. After inoculation of live virus, regular assessment of the macaques for virus burdens and signs of disease, such as rash, lymphadenopathy, or weight loss, will be done. These assays will include qualitative and quantitative analyses of virus burden, antibody production, and various hematologic parameters, including absolute numbers of T-cell subsets and platelets. Plasma levels of SIV virion RNA will be determined by QC-RT-PCR in Dr. Jeff Lifson's laboratory at the NCI-Frederick Cancer Research Center. The overall goal of the Program Project is to develop an effective HIV vaccine that will prevent infection or disease. To identify the best immunogens, adjuvants, and routes of immunization, initial testing of vaccine strategies in the SlV-macaque model is critical before intelligent decisions can be made regarding selection of candidate HIV vaccines for use in Phase I human trials. Thus, the Nonhuman Primate Core is critical for the success of this program project grant.