Primate Studies

灵长类动物研究

• 批准号: 8720871
• 负责人: Preston A Marx
• 金额: $ 22.05万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8720871
• 关键词: AIDS Vaccines; Address; Adjuvant; Alabama; Animals; Antibodies; Antigens; Blood; CCL25 gene; CCL27 gene; Cells; Cellular Immunity; DNA Vaccines; Development; Gagging; HIV; Head; Homing; Humoral Immunities; Immune; Immune response; Immunization; Individual; Intramuscular; Lymph Node Tissue; Macaca; Macaca mulatta; Measures; Mediating; Modeling; Monkeys; Mucosal Immune Responses; Mucosal Immunity; Mucous Membrane; Pennsylvania; Plasmids; Primates; Research; Research Personnel; Route; SIV; Sampling; Testing; Universities; Vaccination; Vaccines; animal efficacy; cell mediated immune response; chemokine; env Genes; novel; novel strategies; plasmid DNA; rectal; research study; trafficking; vaccine evaluation

The development of an effective AIDS vaccine remains one of the highest priorities in HIV-research. Because increasing evidence suggests that an effective vaccine will require both humoral and cellular immunity, this HIV-RAD project proposes to induce and measure both cellular and humoral immunity using plasmid DMAconstructs expressing SIV gag,-pol-env genes plus novel chemokine DNA plasmids to address mucosal cellular and humoral immunity. This proposal describes a new approach to inducing systemic and mucosal immunity. The overall objective of project #3 is to evaluate the potential of intramuscular (IM) delivery of chemokines to enhance mucosal immunity in the SIVmac model. The hypothesis to be tested is that chemokine-induced redirected trafficking of mucosal-homing immune cells to the systemic compartment leads to cellular and humoral mucosal immune responses without mucosal immunization. Mucosal-expressed chemokines CTACK, MECK, TECK will be tested for their individual potential to enhance the mucosal immune response of a systemically delivered SIV DNA vaccine. The vaccination approach will be IM co-immunization of macaques with an optimized SIVgag/pol/env plus each plasmid form of the mucosal-expressed chemokines. The specific aims are: 1 A. To measure antigen specific cell mediated immune responses systemically in blood as well as in the mucosa following intramuscular plasmid co-immunization of rhesus macaques with 3 individual chemokines plus pSIVgag/pol/env. This aim is expanded to test 5 monkeys per group compared to 3 per group in the previous submission. 1B. To measure antigen specific antibody mediated immune responses systemically in blood and lymph node tissues as well as in the mucosa following IM co-immunization of rhesus macaques with individual chemokines plus pSIVgag/pol/env. Samples from animals in 1Awill also be provided to the University of Alabama Birmingham (DAB) group headed by Dr. Jiri Mestecky. 2. To carry out animal efficacy studies using the SIVmac-rhesus model to evaluate a) 1 selected chemokine adjuvant, b) pSIVgag/pol/env plus the control plasmid and c) a 3rd group of 8 will receive control plasmids only. All animals will be inoculated by the rectal route with pathogenic SIVmac251. Materials will be provided to investigators at the TNPRC, University of Pennsylvania (UPenn) and UAB. This aim is expanded to 8 animals per group to increase the statistical power of the experiment.

开发有效的艾滋病疫苗仍然是艾滋病毒研究的最高优先事项之一。 因为越来越多的证据表明有效的疫苗需要体液和细胞 免疫，这个 HIV-RAD 项目建议使用以下方法诱导和测量细胞和体液免疫 质粒 DMA 构建表达 SIV gag、-pol-env 基因以及新型趋化因子 DNA 质粒以解决 粘膜细胞免疫和体液免疫。该提案描述了一种诱导系统性和 粘膜免疫。项目 #3 的总体目标是评估肌内 (IM) 的潜力 递送趋化因子以增强 SIVmac 模型中的粘膜免疫。要检验的假设是 趋化因子诱导粘膜归巢免疫细胞重定向至全身区室 导致细胞和体液粘膜免疫反应而无需粘膜免疫。 将测试粘膜表达的趋化因子 CTACK、MECK、TECK 的个体潜力 增强系统性 SIV DNA 疫苗的粘膜免疫反应。疫苗接种 该方法将使用优化的 SIVgag/pol/env 加上每种质粒形式对猕猴进行 IM 联合免疫 粘膜表达的趋化因子。具体目标是： 1 A. 系统性地测量血液和体液中抗原特异性细胞介导的免疫反应 恒河猴肌内质粒与 3 种趋化因子联合免疫后的粘膜 加上 pSIVgag/pol/env。这一目标扩大到每组测试 5 只猴子，而实验中每组只测试 3 只猴子。 之前提交的内容。 1B.系统地测量血液和淋巴液中抗原特异性抗体介导的免疫反应 恒河猴与个体进行 IM 联合免疫后的淋巴结组织以及粘膜中 趋化因子加上 pSIVgag/pol/env。 1A中的动物样本也将提供给大学 由 Jiri Mestecky 博士领导的阿拉巴马伯明翰 (DAB) 小组。 2. 使用SIVmac-rhesus模型进行动物功效研究，以评估a) 1种选定的趋化因子 佐剂，b) pSIVgag/pol/env 加上对照质粒，c) 第三组 8 个将接受对照质粒 仅有的。所有动物都将通过直肠途径接种致病性 SIVmac251。材料将是 提供给 TNPRC、宾夕法尼亚大学 (UPenn) 和 UAB 的研究人员。这个目标扩大了 每组8只动物以增加实验的统计功效。