Ginkgo Biloba Enhances Therapeutic HIV Vaccination

描述（由申请人提供）：本提案的总体目标是研究银杏叶对HIV治疗性疫苗的有益作用。我们的初步研究表明，银杏叶中的一种成分银杏内酯a可以增强cd14 +单核细胞衍生的树突状细胞（DC）的分化和激活，表明银杏内酯a在引发免疫应答中具有积极的调节作用。此外，研究表明DC疫苗可能是治疗慢性HIV-1感染者的一种有希望的策略。统一的假设是，用HIV病毒样颗粒（VLPs）和银杏叶成分的混合物免疫可能增强HIV病毒样颗粒单独诱导的免疫反应。我们拟在CD4 KO小鼠模型中研究银杏叶中不同成分在增强体液和细胞免疫应答中的辅助作用。在我们的研究中提出了两个具体目标。Aim 1的研究旨在确定银杏叶是否能增强HA/SHIV VLP免疫小鼠模型中的SIV Gag和HIV Env特异性免疫反应。我们将研究银杏叶中不同成分对增强HA/SHIV VLPs鼻内免疫并每日给予银杏叶成分治疗的CD4 KO小鼠模型的体液和细胞免疫应答的辅助作用。Aim 2的研究旨在比较银杏叶调节DC活化和抗原呈递功能的分子机制。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，银杏叶中对增强抗HIV抗原免疫反应最有效的成分将在CD4+ T细胞计数低的SHIV感染恒河猴中进行评估。我们将比较vlp免疫的SHIV感染猴子的疾病进展，以评估我们的银杏叶和vlp混合物作为治疗性疫苗的功效。本研究结果将有助于揭示银杏叶对HIV治疗性疫苗的增强作用，并进一步阐明补充替代医学（CAM）的作用机制和益处。此外，它将有可能启动转化和早期临床试验，以研究这种CAM和VLPs治疗艾滋病毒/艾滋病及其并发症的方法。

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.