Non-Human Primates

非人类灵长类动物

基本信息

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
项目类别：
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

项目摘要

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.

非人类灵长类动物核心（Core B）将为所有临床前测试提供人员和分析方法猪尾猕猴（Macaca nemestrina）的候选疫苗。用于评估的SLV抗原免疫原将由博士开发。 Hahn 和 Compans，如项目 1 和 2 中所述，分别包含 SlVmac239 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博士。 Moldoveanu 和 Mestecky 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对猕猴进行免疫：皮内和/或鼻内接种免疫原，表征 SlV 特异性肱骨和细胞血液和粘膜分泌物中的免疫反应，通过静脉注射或直肠内途径使用致病性 SlY 菌株，并评估保护水平。期间免疫期间，将评估 SIV 特异性体液和细胞免疫反应 IgG、IgA 和中和抗体的产生以及抗原特异性增殖反应淋巴细胞。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感染迹象疾病，如皮疹、淋巴结肿大或体重减轻，将会发生。这些检测将包括病毒负荷、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量。 SIV 病毒颗粒 RNA 的血浆水平将在 NCI-弗雷德里克癌症研究中心 Jeff Lifson 博士的实验室中通过 QC-RT-PCR 进行测定。该计划项目的总体目标是开发一种有效的艾滋病毒疫苗来预防感染或疾病。为了确定最佳的免疫原、佐剂和免疫途径，在就选择用于 I 期人体试验的候选 HIV 疫苗做出明智决策之前，在 SlV-猕猴模型中对疫苗策略进行初步测试至关重要。因此，非人类灵长类核心对于该计划项目拨款的成功至关重要。