Ginkgo Biloba Enhances Therapeutic HIV Vaccination

描述(申请人提供)：这项建议的总体目标是研究银杏对HIV治疗性疫苗的有益影响。我们的初步研究表明，银杏内酯A可以促进CD14+单核细胞来源的树突状细胞(DC)的分化和激活，表明银杏内酯A在诱导免疫反应中具有正向调节作用。此外，研究表明，DC疫苗可能是治疗慢性HIV-1感染者的一种有前途的策略。统一的假设是，用HIV病毒样颗粒(VLP)和银杏成分的混合物免疫可能会增强单独由HIV VLP诱导的免疫反应。我们建议研究银杏叶中每种不同成分在增强体液免疫和细胞免疫反应方面的佐剂作用。我们的研究提出了两个具体目标。目的1的研究旨在确定银杏叶是否能增强HA/SHV VLP免疫小鼠模型中的SIV Gag和HIV Env特异性免疫反应。我们将研究银杏叶不同成分在增强CD4KO小鼠体液免疫和细胞免疫方面的佐剂作用。该模型是用HA/SIV VLP滴鼻免疫小鼠，并用银杏叶成分(S)每日治疗。目的2的研究旨在比较银杏叶调节DC激活和抗原提呈功能的分子机制。我们还将研究银杏叶处理激活的信号转导通路。在未来的研究中，银杏中最有效的成分(S)在增强对艾滋病毒抗原的免疫反应方面具有最有效的作用，将被推进用于评价感染希沃氏病毒的低CD_4+T细胞计数的恒河猴。我们将比较VLP免疫的SIV感染猴子的疾病进展，以评估我们的银杏和VLP混合物作为治疗性疫苗的有效性。这项研究的结果将有助于深入了解银杏叶对HIV治疗性疫苗的增强作用，并进一步阐明使用补充和替代医学(CAM)的机制和好处。此外，它将有可能启动翻译和早期临床试验，以研究这种治疗艾滋病毒/艾滋病及其并发症的CAM和VLP方法。

DESCRIPTION (provided by applicant): The overall objective of this proposal is to study the beneficial effects of Ginkgo biloba on HIV therapeutic vaccines. Our preliminary studies demonstrate that a component from the Ginkgo biloba, Ginkgolide A, can act to enhance the differentiation and activation of CD 14+ monocyte-derived Dendritic cells (DC), indicating a positive modulating function of Ginkgolide A in eliciting immune responses. Furthermore, it has been shown that DC vaccines could be a promising strategy for treating people with chronic HIV-1 infection. The unifying hypothesis is that immunization with mixtures of HIV virus-like particles (VLPs) and Ginkgo biloba components may enhance the immune responses induced by HIV VLPs alone. We propose to investigate the adjuvant effect of each different component in Ginkgo Biloba in enhancing both the humoral and the cellular immune responses in a CD4 KO mouse model. Two Specific Aims are proposed in our studies. Studies in Aim 1 are designed to determine if Ginkgo biloba enhances SIV Gag and HIV Env specific immune responses in HA/SHIV VLP immunized mouse model. We will investigate the adjuvant effect of different components in Ginkgo biloba in enhancing both humoral and cellular immune responses in a CD4 KO mouse model which are intranasally immunized with HA/SHIV VLPs with daily treatment by Ginkgo biloba component(s). Studies in Aim 2 are designed to compare molecular mechanism of Ginkgo biloba modulating DC activation and antigen-presentation function. We will also investigate signal transduction pathways activated by Ginkgo biloba treatment. In future studies, the component(s) in Ginkgo biloba that has the most potent effect in enhancing immune responses against HIV antigens will be advanced for evaluation in SHIV infected rhesus monkeys with low CD4+ T cell counts. We will compare disease progression with VLP-immunized SHIV infected monkeys to evaluate efficacy of our Ginkgo biloba and VLPs mixture as a therapeutic vaccine. The results obtained from the proposed research will help to provide insights into the enhancement effect of Ginkgo biloba on HIV therapeutic vaccine, and to further elucidate the mechanism and benefits of using complementary and alternative medicine (CAM). Furthermore, it will have the potential to initiate translational and early phase clinical trials to investigate this CAM and VLPs approach to treat HIV/AIDS and its complications.