Novel Prophylactic HIV Vaccines Based on rAAV Vectors

基于 rAAV 载体的新型预防性 HIV 疫苗

• 批准号: 6682291
• 负责人: Philip R Johnson
• 金额: $ 77.6万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-29 至 2004-09-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6682291
• 关键词: AIDS vaccines; adeno associated virus group; gene delivery system; human immunodeficiency virus 1; recombinant virus; vaccine development; vector vaccine

DESCRIPTION (provided by applicant): The overall goal of this HIVRAD Program is to develop a second generation HIV -1 vaccine based on recombinant adeno-associated virus (rAAV) vectors. The proposed research in this application builds on our experience with a first generation rAAV /HIV vaccine that is being readied for human trials. Although the first generation vaccine is a promising candidate, we believe that substantial room for improvement remains. Based on our preliminary data, we have developed a series of hypothesis driven experiments in Projects 1 -4 to achieve this goal. Two major themes will be developed. First, we will enhance antigen- specific T cell responses to the vaccine by (i) significantly augmenting vaccine gene delivery (Projects 1 and 2) and (ii) directly engaging and modifying host immune responses (Projects 1 and 3). Second, through a novel and innovative approach, we will generate serum antibodies that neutralize primary isolates of HIV -1 by using rAAV vectors to transfer human antibody genes of predetermined specificity to skeletal muscle (project 4). The convergence of these themes will form the basis of the second-generation rAAV /HIV vaccine. Two important and intended by-products of this Program will be: (i) a better understanding of how gene-based vaccines actually work (Project 3); and, (b) improved vectors for general gene delivery to muscle (Project 2). The entire Program will be supported by four Cores. Core A is the Administrative Office, and as such will coordinate the Program and ensure the timely execution of the proposed research. Core B will serve as the central testing facility for non-human primates. Core C is the non-human primate immunology core and is directly affiliated with Core B. Core D supports viral vector production for the Program.

描述（由申请人提供）：本HIVRAD计划的总体目标是开发基于重组腺相关病毒（rAAV）载体的第二代HIV-1疫苗。这项申请中的拟议研究建立在我们对第一代rAAV /HIV疫苗的经验基础上，该疫苗正准备进行人体试验。虽然第一代疫苗是一个有希望的候选者，但我们认为仍有很大的改进余地。根据我们的初步数据，我们在项目1 - 4中开发了一系列假设驱动的实验来实现这一目标。将制定两大主题。首先，我们将通过（i）显著增强疫苗基因递送（项目1和2）和（ii）直接参与和修饰宿主免疫应答（项目1和3）来增强对疫苗的抗原特异性T细胞应答。第二，通过一种新的创新方法，我们将通过使用rAAV载体将预定特异性的人抗体基因转移到骨骼肌来产生中和HIV-1原代分离株的血清抗体（项目4）。这些主题的融合将构成第二代rAAV /HIV疫苗的基础。该计划的两个重要和预期的副产品将是：（i）更好地了解基因疫苗实际上是如何工作的（项目3）;（B）改进载体，用于将一般基因传递到肌肉（项目2）。整个计划将由四个核心支持。核心A是行政办公室，因此将协调该计划，并确保及时执行拟议的研究。核心B将作为非人灵长类动物的中心试验机构。核心C是非人灵长类动物免疫学核心，直接隶属于核心B。核心D支持该计划的病毒载体生产。