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）：Powder Intagines，Inc。（PJV）和匹兹堡大学的计划项目应用，需要使用拟南芥免疫缺陷病毒（HIV）感染的治疗性DNA疫苗治疗方案评估。猕猴中的模型。要评估的治疗性DNA疫苗是一种基于CMV启动子的DNA疫苗载体，该疫苗载体编码SIVMAC239的17E FR克隆的GAG，RT和NEF产物。该疫苗将使用临床预处理的颗粒介导的（基因枪）输送装置进行输送，该装置已显示出可引起人类和猴子中的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，该疫苗是通过葛兰素史克（GSK）和PJV的联合临床开发工作进行临床评估的临床轨迹。因此，本应用中描述的活动是GSK/PJV临床共同开发工作的组成部分，用于预防性和治疗性艾滋病疫苗，并将提供三个重要功能以促进临床成功。首先，这些活动将在高度相关的SIV/Rhesus Monkey模型中，提供GSK临床DNA疫苗媒介策略的免疫原性和治疗疫苗潜力的非人类灵长类动物模型验证。我们最近使用较早载体的恒星模型中的DNA疫苗试验证明了我们通过粒子介导的DNA疫苗技术诱导明显的预防性和治疗作用的能力，此外，这些活动还可以评估令人兴奋的新DNA疫苗辅助矢量编码大肠杆菌的热量肠毒素。在广泛的非人类灵长类动物安全试验中，该辅助载体已被证明是安全的，并大大增加了小鼠和猴子对各种模型抗原的Th1细胞免疫反应。最后，本应用中描述的活动将提供有关在恒河猴SIV模型中治疗性DNA疫苗接种后（有无辅助）后的全身和粘膜免疫和病毒负荷抑制的重要机械数据。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，粘膜免疫和肠道病毒储层的重要性以及DC / T细胞相互作用在治疗性DNA疫苗中的重要性功效。