Optimizing the immunogenicity of next generation polyvalent HIV vaccine formulati

项目1将侧重于优化下一代多价环境艾滋病毒疫苗配方，使用 多基因、多价DMA主蛋白Boost技术平台。 我们的第一种艾滋病毒疫苗配方DP6-001是几年前开发的，用于概念验证试验，以 在人类志愿者身上展示了DMA主要蛋白增强方法的免疫原性。这个 20世纪90年代中期从HIV感染者中分离出的初级Env抗原是基于以下因素随机选择的 他们的基因分支。艾滋病毒疫苗领域的快速进步现在为我们提供了更多的选择 主要的环境抗原，特别是过去研究较少的分支的环境蛋白和环境蛋白 含有更详细的病毒分离患者信息的蛋白质。此外, 新近建立的伪型中和试验和新建立的靶向HIV-1病毒 专家小组(“分级制度”)提供了一个可衡量的标准，以指导我们选择更相关的主要课程 用于开发以诱导中和抗体为重点的HIV疫苗的环境抗原 回应。利用上述进展，我们鉴定了一组主要的env抗原。 能够产生比我们以前配方中包含的中和抗体更广泛的中和抗体 DP6-001。在这一IPCAVD方案目前的项目1中，将进行以下研究： 目的1敲定下一代多价环状病毒制剂的筛选，以进一步提高产品质量 中和抗体活性。 目的2选择一种免疫原佐剂作为下一代蛋白质Boost的一部分 多价环境配方。 目的3检测新一代多价环状病毒制剂在DMA启动时的免疫原性。 由电穿孔方法传递。 目的4检测DMA Prime-Protein Boost法诱导的免疫血清中的表位分布。 确定负责中和活性的抗体的表位特异性。

Project 1 will focus on the optimization of the next generation polyvalent Env HIV vaccine formulations using the multi-gene, polyvalent DMA prime - protein boost technology platform. Our first HIV vaccine formulation, DP6-001, was developed several years ago for a proof-of-concept trial to demonstrate the immunogenicity of the DMA prime - protein boost approach in human volunteers. The primary Env antigens isolated from HIV infected patients in mid-1990s were selected randomly based on their genetic clades. Rapid progress in the HIV vaccine field now provides us with a much larger selection of primary Env antigens, especially those Env proteins from clades less studied in the past and those Env proteins with more detailed information about the patients from whom the viruses were isolated. In addition, the recently developed pseudotyped neutralization assay and newly established target HIV-1 primary virus panel ("the Tiers System") provides a measurable standard to guide our selection of more relevant primary Env antigens for the development of HIV vaccines focusing on the induction of neutralizing antibody responses. By taking advantage of the above progress, we have identified a group of primary Env antigens that were able to elicit much broader neutralizing antibodies than those included in our previous formulation DP6-001. In the current Project 1 of this IPCAVD program, the following studies will be conducted: Aim 1 To finalize the selection of next generation polyvalent Env formulation to further improve the quality of neutralizing antibody activities. Aim 2 To select an immunogenic adjuvant to be used as part of the protein boost for the next generation polyvalent Env formulation. Aim 3 To test the immunogenicity of next generation polyvalent Env formulation when the DMA priming is delivered by the electroporation method. Aim 4 To examine the epitope profiles in immune sera elicited by DMA prime-protein boost approach and identify the epitope specificities of antibodies responsible for the neutralizing activities.