Novel Prophylactic HIV Vaccines Based on rAAV Vectors

描述(由申请人提供)： 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。这项申请中拟议的研究建立在我们对第一代rAAV/HIV疫苗的经验基础上，该疫苗目前正在第一阶段人体试验中进行测试。虽然第一代疫苗是一个很有希望的候选疫苗，但我们认为仍有很大的改进空间。基于我们的初步数据，我们开发了一系列假设驱动的实验来实现这一目标。我们将通过(I)显著增加疫苗的基因传递和(Ii)直接接触和修改宿主免疫反应来增强抗原特异性T细胞对疫苗的反应。

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 now being tested in Phase I 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 to achieve this goal. We will enhance antigen-specific T cell responses to the vaccine by (i) significantly augmenting vaccine gene delivery and (ii) directly engaging and modifying host immune responses.