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，一种有效的疫苗需要体液和细胞两种因素 免疫，这个HIV-RAD项目建议用来诱导和测量细胞和体液免疫 表达SIV gag、-pol-env基因和新型趋化因子DNA质粒的质粒DNA构建 粘膜细胞免疫和体液免疫。这项提议描述了一种新的方法，以诱导系统性和 粘膜免疫。项目3的总体目标是评估肌肉内注射(IM)的潜力 在SIVmac模型中传递趋化因子以增强粘膜免疫。需要检验的假设是 趋化因子诱导的黏膜归巢免疫细胞重定向运输到全身各室 导致细胞和体液黏膜免疫反应，而不是粘膜免疫。 将测试粘膜表达的趋化因子CTACK、Meck、Teck的个体潜力 增强系统递送的SIV DNA疫苗的粘膜免疫应答。接种疫苗 方法将是通过优化的SIVgag/Poll/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.系统地测量血液中抗原特异性细胞免疫反应 3种单独趋化因子肌肉注射质粒联合免疫猕猴后的粘膜 加上pSIVgag/pol/env。这一目标被扩大到每组测试5只猴子，而在 以前提交的材料。 1B.系统检测血液和淋巴中抗原特异性抗体介导的免疫反应 猕猴与个体IM联合免疫后结节组织和粘膜组织的变化 趋化因子加pSIVgag/pol1/env。来自1A的动物样本也将提供给加州大学 由Jiri Mestecky博士领导的阿拉巴马州伯明翰(DAB)小组。 2.使用SIVmac-Rheesus模型进行动物疗效研究，以评估a)选择的趋化因子 佐剂，b)pSIVgag/pol/env加上对照质粒，以及c)第三组8人将接受对照质粒 只有这样。所有动物将通过直肠途径接种致病SIVmac251。材料将是 提供给TNPRC、宾夕法尼亚大学(UPenn)和UAB的调查人员。这一目标被扩大了 每组8只动物，以增加实验的统计能力。