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.

有效辅助疫苗的开发仍然是HIV研究中最高的优先事项之一。 因为越来越多的证据表明有效的疫苗需要体液和细胞 免疫力，该HIV-RAD项目提议使用使用 表达SIV GAG，-POL-ENV基因以及新型趋化因子DNA质粒以解决的质粒DMACONSTRUCTS以解决 粘膜细胞和体液免疫。该建议描述了一种诱导系统性和的新方法 粘膜免疫。项目＃3的总体目标是评估肌内（IM）的潜力 趋化因子递送以增强SIVMAC模型中的粘膜免疫。要检验的假设是 趋化因子诱导的粘膜含免疫细胞的重定向运输到全身室 导致没有粘膜免疫的细胞和体液粘膜免疫反应。 粘膜表达的趋化因子CTACK，MECK，TECK将对他们的个人潜力进行测试 增强系统递送的SIV DNA疫苗的粘膜免疫反应。疫苗接种 方法将与优化的sivgag/pol/env加上每种质粒形式共同免疫猕猴 粘膜表达的趋化因子。具体目的是： 1 A.测量抗原特异性细胞在血液以及在 粘膜内猕猴与3个单个趋化因子猕猴共免疫粘膜粘膜 加上PSIVGAG/POL/ENV。该目标扩展到每组测试5只猴子，而每组中的3只猴子 先前的提交。 1B。测量抗原特异性抗体在血液和淋巴上系统地介导的免疫反应 恒河猴与单个共同免疫后，节点组织以及粘膜中的粘膜 趋化因子加PSIVGAG/POL/ENV。还向大学提供了1个动物的样本 阿拉巴马州伯明翰（DAB）小组由Jiri Mestecky博士领导。 2。使用SIVMAC六链甲固定模型进行动物疗效研究以评估A）1选择的趋化因子 辅助，b）psivgag/pol/env加控制质粒，c）第三组8将接收控制质粒 仅有的。所有动物将通过致病性SIVMAC251接种直肠途径。材料将是 提供给宾夕法尼亚大学（UPENN）和UAB的TNPRC的调查人员。这个目标扩大了 每组8只动物以增加实验的统计能力。