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An Adjuvanted Therapeutic DNA Vaccine for AIDS

艾滋病辅助治疗性 DNA 疫苗

基本信息

批准号：
7009291
负责人：
Michael A Murphey-Corb
金额：
$ 77.63万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-01 至 2007-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7009291
关键词：
Adjuvanted Therapeutic DNA Vaccine AIDS

项目摘要

DESCRIPTION (provided by applicant): The program project application of PowderJect Vaccines, Inc. (PJV) and the University of Pittsburgh entails the evaluation of a therapeutic DNA vaccine regimen for human immunodeficiency virus (HIV) infection using the simian immunodeficiency virus (SIV) model in rhesus macaques. The therapeutic DNA vaccine to be evaluated is a single, CMV promoter-based DNA vaccine vector encoding the gag, RT, and nef products of the 17e Fr clone of SIVmac239. This vaccine will be delivered using the clinically-proven particle-mediated (gene gun) delivery device that has been shown to elicit Th1 humoral and cellular responses in man and monkeys. The design of the SIV DNA vaccine vector is intended to closely mimic a clinical HIV-1 DNA vaccine vector that is on a clinical track for human evaluation via the joint clinical development efforts of GlaxoSmithKline (GSK) and PJV. Therefore, the activities described in this application are an integral part of the GSK/PJV clinical co-development efforts for prophylactic and therapeutic AIDS vaccines and will serve three important functions to promote clinical success. First, these activities will provide non-human primate model validation of the immunogenicity and therapeutic vaccine potential of GSK's clinical DNA vaccine vector strategy in the highly relevant SIV/rhesus monkey model. Our recent DNA vaccine trials in the rhesus model using earlier vectors have proven our ability to induce significant prophylactic and therapeutic effects via particle-mediated DNA vaccine technology, in addition, these activities will allow for the evaluation of an exciting new DNA vaccine adjuvant vector encoding the heat-labile enterotoxin of E. coli. This adjuvant vector has been proven safe in an extensive nonhuman primate safety trial and dramatically augments Th1 cellular immune responses to a variety of model antigens in mice and monkeys. Finally, activities described in this application will provide important mechanistic data regarding the induction of systemic and mucosal immunity and virus load containment following therapeutic DNA vaccination (with and without adjuvant) in the rhesus SIV model. Specifically, the proposed therapeutic DNA vaccine trials will allow for determination of the importance of the strength and quality of systemic cellular responses, the role of mucosal immunity and importance of gut viral reservoirs, and the importance of DC / T cell interactions in therapeutic DNA vaccine efficacy.

描述（由申请人提供）：PowderJect Vaccines, Inc. （PJV）和匹兹堡大学的项目申请涉及使用恒河猴猴免疫缺陷病毒（SIV）模型对人类免疫缺陷病毒（HIV）感染的治疗性DNA疫苗方案进行评估。待评估的治疗性DNA疫苗是一种基于CMV启动子的单一DNA疫苗载体，编码SIVmac239的17e Fr克隆的gag、RT和nef产物。该疫苗将使用经临床验证的颗粒介导（基因枪）递送装置进行递送，该装置已被证明可在人和猴子中引发Th1体液和细胞反应。SIV DNA疫苗载体的设计旨在密切模仿临床HIV-1 DNA疫苗载体，该载体通过葛兰素史克（GSK）和PJV的联合临床开发工作正在临床轨道上进行人体评估。因此，本申请中描述的活动是GSK/PJV在预防和治疗性艾滋病疫苗临床合作开发工作的组成部分，并将发挥三个重要作用，以促进临床成功。首先，这些活动将提供非人灵长类动物模型验证GSK的临床DNA疫苗载体策略在高度相关的SIV/恒河猴模型中的免疫原性和治疗性疫苗潜力。我们最近使用早期载体在恒河猴模型中进行的DNA疫苗试验证明，我们能够通过颗粒介导的DNA疫苗技术诱导显着的预防和治疗效果，此外，这些活动将允许评估编码大肠杆菌热不稳定肠毒素的令人兴奋的新的DNA疫苗佐剂载体。该佐剂载体已在一项广泛的非人灵长类动物安全性试验中被证明是安全的，并显著增强了小鼠和猴子对多种模型抗原的Th1细胞免疫反应。最后，本应用中描述的活动将为恒河猴SIV模型中治疗性DNA疫苗接种（有或没有佐剂）诱导全身和粘膜免疫以及病毒负荷抑制提供重要的机制数据。具体而言，拟议的治疗性DNA疫苗试验将允许确定全身细胞反应的强度和质量的重要性，粘膜免疫的作用和肠道病毒库的重要性，以及DC / T细胞相互作用在治疗性DNA疫苗疗效中的重要性。