Non-Human Primates

非人类灵长类动物

• 批准号: 7899515
• 负责人: Patricia N Fultz
• 金额: $ 12.71万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-26 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7899515
• 关键词: Adenovirus Vector; Adjuvant; Animals; Antibody Formation; Antigens; Biological Assay; Blood; Blood Platelets; Blood specimen; Body Weight decreased; Cells; Computer Simulation; Consensus Sequence; Disease; Disease Progression; Dose; Down-Regulation; Evaluation; Exanthema; Family suidae; Gagging; Genes; Goals; HIV; HIV Infections; HIV vaccine; Human; Human Resources; Immune; Immune response; Immune system; Immunization; Immunoglobulin A; Immunologics; Infection; Infection prevention; Interferons; Intramuscular; Intranasal Administration; Intravenous; Laboratories; Life; Lymphatic Diseases; Lymphocyte; Macaca; Macaca nemestrina; Mediating; Modeling; Monitor; Mucosal Immune Responses; Mucous Membrane; Mus; NCI Center for Cancer Research; Peptides; Phase; Plasma; Preclinical Testing; Production; Program Research Project Grants; Protocols documentation; RNA; Recombinant DNA; Relative (related person); Rodent; Route; SIV; Satellite Viruses; T-Lymphocyte Subsets; Tail; Testing; Time; Treatment Protocols; Vaccination; Vaccines; Viral Load result; Virion; Virus; Virus-like particle; Work; base; candidate selection; immunogenicity; neutralizing antibody; nonhuman primate; novel; novel virus; prevent; programs; protective efficacy; rectal; research study; response; success; tissue culture; transmission process; vaccine candidate; vaccine evaluation

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.

非人灵长类核心（核心B）将为所有临床前试验提供人员和检测方法， 猪尾猕猴（Macaca nemestrina）的候选疫苗。用于评价的SIV抗原， 免疫原将由Hahn博士和Compans博士开发，如项目1和2所述， 并且将包括SIVmac 239和SIVsm/mac共有序列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 由Molecanu和Mestecky博士，项目4，也将进行测试，以增强系统和 粘膜免疫反应。每个实验方案将包括免疫猕猴， 免疫原的皮内和/或鼻内接种，表征SIV特异性肱骨和细胞免疫应答。 血液和粘膜分泌物中的免疫应答，通过静脉内或 直肠内途径与致病性SlY菌株接触，并评估保护水平。期间 在免疫期间，将评价SIV特异性体液和细胞免疫应答， IgG、伊加和中和抗体的产生，以及 淋巴细胞一些血液样本将被送往Letvin博士的实验室（项目3）进行分析， 淋巴细胞响应代表整个gag基因的肽库产生干扰素-G。 接种活病毒后，定期评估猕猴的病毒负荷和 疾病，如皮疹，淋巴结病，或体重减轻，将做。这些分析将包括 病毒负荷、抗体产生和各种血液学指标的定性和定量分析 参数，包括T细胞亚群和血小板的绝对数量。将在NCI-Frederick癌症研究中心的Jeff Lifson博士实验室通过QC-RT-PCR测定SIV病毒体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，以预防感染或疾病。为了鉴定最佳的免疫原、佐剂和免疫途径，在SIV-猕猴模型中对疫苗策略进行初始测试是至关重要的，然后才能做出关于选择候选HIV疫苗用于I期人体试验的明智决定。因此，非人类灵长类核心是这个项目资助的成功至关重要。