Novel immune stimulating adjuvants for an HIV DNA Vaccine

描述（由申请人提供）：本文件包含专有信息，除非用于审查和评估，否则Profectus BioSciences不要求向政府以外的人员发布。DNA疫苗的安全性、稳定性和产品开发速度的提高使其成为开发预防性和治疗性HIV疫苗的一种有吸引力的方法。不幸的是，成功的灵长类动物DNA疫苗接种需要多次接种不受欢迎的大剂量质粒。基因编码佐剂可以提供免疫刺激和剂量节约效应，以实现实用的基于dna的HIV疫苗。我们的辅助方法利用RIG-1信号级联，识别病毒病原体感染并触发先天免疫反应。我们构建了rig -1样解旋酶及其接头蛋白（IPS-1）的显性阳性版本，当作为质粒DNA转染到细胞中时，它们可以模拟病毒感染。我们的目的是确定这些表达RIG-1的质粒是否比“基准”佐剂IL-12在更大程度上辅助小鼠HIV DNA疫苗。我们将通过以下具体目标来实现我们的目标：(1)确定一种佐剂或佐剂组合，诱导最大的B细胞和T细胞介导的针对HIV GP160的免疫反应；(2)证明铅佐剂在牛痘- hiv攻击模型中提供了增强的保护。在小鼠中具有免疫原性和保护性的联合制剂将在其他小鼠和灵长类动物研究中作为后续II期SBIR应用的高级HIV DNA疫苗的组成部分进行评估。2

DESCRIPTION (provided by applicant): This document contains proprietary information that Profectus BioSciences requests not be released to persons outside the Government, except for purposes of review and evaluation. Abstract The enhanced safety, stability, and accelerated product development generally provided by DNA vaccination make it an appealing approach to develop prophylactic and therapeutic HIV vaccines. Unfortunately, successful DNA vaccination of primates requires multiple inoculations with undesirably large doses of plasmid. Genetically encoded adjuvants could provide the immune stimulating and dose-sparing effects necessary to realize a practical DNA-based vaccine for HIV. Our adjuvant approach exploits the RIG-1 signaling cascades that recognize infection with viral pathogens and trigger innate immune responses. We have constructed dominant-positive versions of RIG-1-like helicases and their adaptor protein (IPS-1) that mimic viral infection when transfected into cells as plasmid DNA. Our objective is to determine whether these plasmid expressed RIG-1 based constructs will adjuvant an HIV DNA vaccine in mice to a greater extent than the "bench mark" adjuvant IL-12. We will pursue our objective through the following specific aims: (1) Identify an adjuvant or adjuvant combination that induces maximal B and T cell mediated immune responses against HIV GP160; (2) Demonstrate that the lead adjuvant provides enhanced protection in a Vaccinia-HIV challenge model. The co-formulation that is immunogenic and protective in mice will be evaluated in additional mice and primate studies as components of an advanced HIV DNA vaccine in follow-on Phase II SBIR applications. 2 PUBLIC HEALTH RELEVANCE: The objective of this project is to develop novel adjuvants for an HIV DNA vaccine. Such a vaccine/adjuvant combination is needed to combat the HIV epidemic.