Whole Autologous SIV Vaccine Using Dendritic Cells

描述：（由申请人提供）抗逆转录病毒治疗（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应答的治疗方法， 特别是T细胞反应，是迫切需要的。理想抗原 在活动性感染期间用于疫苗递送的来源是自体的 病毒，因为它含有所有适合于 特殊感染。通过树突状细胞（DC）递送病毒抗原将 是最佳的，因为DC是专业的抗原呈递细胞， 刺激体内T细胞应答。Barratt-Boyes博士及其同事 显示DC具有从活细胞获得抗原以交叉呈递给T细胞独特能力。DC也从游离的病毒颗粒获得抗原 以及凋亡和坏死细胞。利用猕猴Macaquehimian 免疫缺陷病毒（SIV）模型，Barratt-Boyes博士 和同事们将比较这些通过DC获得抗原的方法， 刺激病毒特异性T细胞反应的目的。利用最优 提供交叉呈递的病毒抗原的方法，他们将开发一种 使用自体免疫的基于DC的定制SIV感染治疗性疫苗 病毒抗原猴在慢性SIV感染期间将接种疫苗， 原代病毒分离株，并在接受抗逆转录病毒治疗时，接近临床HIV 感染和治疗。这些研究旨在提供一个重要的原理证明 使用自体全病毒疫苗治疗已建立的HIV 感染有3个具体目标：（1）表征和优化交叉- B j猴DC体外提呈SIV抗原的能力 DC在体外刺激对自体SIV的多克隆T细胞应答;和 (3)为了测试抗原负载DC增强对自体免疫的能力， 体内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.