Whole Autologous SIV Vaccine Using Dendritic Cells

描述：(由申请人提供)抗逆转录病毒疗法(ART)不是 足以控制人类免疫缺陷病毒(HIV)感染；以及 刺激病毒特异性免疫反应的治疗方法， 尤其是T细胞反应，是迫切需要的。理想的抗原 活动性感染期间提供疫苗的来源是自体的 病毒，因为它包含与病毒相适应的所有抗原 特定的感染。通过树突状细胞(DC)传递病毒抗原将 是最佳的，因为DC是专业的抗原提呈细胞， 在体内激发T细胞反应。巴拉特-博耶斯博士和他的同事们 研究表明，DC具有从活细胞中获取抗原以交叉提呈给T细胞的独特能力。DC也从游离的病毒颗粒中获得抗原 以及来自凋亡和坏死性细胞。使用恒河猴 免疫缺陷病毒(SIV)模型，Barratt-Boyes博士 和同事们将比较DC获取抗原的这些方法 刺激病毒特异性T细胞反应的目的。使用最优的 提供病毒抗原用于交叉呈现的方法，它们将开发出一种 自体DC为基础的SIV感染定制治疗性疫苗 病毒抗原。猴子将在慢性SIV感染期间接种疫苗 初步分离病毒，同时接受抗逆转录病毒治疗，以接近临床艾滋病毒 感染和治疗。这些研究的目的是提供一个重要的原则证明 使用自体全病毒疫苗治疗已确定的艾滋病毒 感染。具体目标有三个：(1)对交叉模型进行表征和优化。 SIV抗原bj猴DC的体外提呈；(2)测定其免疫原性 DC在体外刺激多克隆T细胞对自体SIV的反应；以及 (3)检测抗原负载DC对自体免疫的增强能力。 体内的SIV。

DESCRIPTION: (provided by applicant) Antiretroviral therapy (ART) is not sufficient to control human immunodeficiency virus (HIV) infection, and therapeutic approaches to stimulate virus-specific immune responses, particularly T cell responses, are urgently needed. The ideal antigen source for vaccine delivery during active infection is autologous virus, because it contains all antigens appropriate to the specific infection. Delivery of viral antigens via dendritic cells (DC) would be optimal, as DC are professional antigen-presenting cells that potently stimulate T cell responses in vivo. Dr Barratt-Boyes and colleagues have shown that DC have a unique capacity to acquire antigens from live cells for cross-presentation to T cells. DC also acquire antigens from free viral particles and from apoptotic and necrotic cells. Using the rhesus macaquehimian immunodeficiency virus (SIV) model, Dr. Barratt-Boyes and colleagues will compare these methods of acquisition of antigen by DC for the purposes of stimulating virus-specific T cell responses. Using the optimal method of providing viral antigens for cross-presentation, they will develop a DC-based tailor-made therapeutic vaccine for SIV infection using autologous viral antigens. Monkeys will be vaccinated during chronic SIV infection with a primary virus isolate and while receiving ART, to approximate clinical HIV infection and therapy. The studies aim to provide an importanl proof-of-principle for using autologous, whole virus vaccines for the treatment of established HIV infection. There are 3 specific aims: (1) To characterize and optimize cross- presentation of SIV antigens b j monkey DC in vitro; (2) To determine the capacity for DC to stimulate polyclonal T cell responses to autologous SIV in vitro; and (3) To test the capacity for antigen-loaded DC to augment immunity to autologous SIV in vivo.