Optimizing the immunogenicity of next generation polyvalent HIV vaccine formulati

优化下一代多价 HIV 疫苗配方的免疫原性

• 批准号: 8499206
• 负责人: Shan Lu
• 金额: $ 234.3万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2016-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8499206
• 关键词: Adjuvant; Antibodies; Antibody Binding Sites; Antibody Formation; Antibody Specificity; Biological Assay; Biological Markers; Cellular Immunity; Clinical Research; Clinical Trials; DNA; DNA Vaccines; Data; Development; Drug Formulations; Electroporation; Epitopes; Equilibrium; Future; Genes; Genetic; HIV; HIV vaccine; HIV-1; Human; Human Volunteers; Immune Sera; Immune response; Immunization; Injection of therapeutic agent; Intramuscular; Manuscripts; Measurable; Methods; Monitor; Needles; Oryctolagus cuniculus; Patients; Phase; Proteins; Publishing; QS21; Safety; Serum; System; Technology; Testing; Vaccines; Viral; Virus; Work; base; design; env Gene Products; immunogenic; immunogenicity; improved; neutralizing antibody; next generation; pre-clinical; preclinical study; programs; screening; vaccine development; Adjuvant; Antibodies; Antibody Binding Sites; Antibody Formation; Antibody Specificity; Biological Assay; Biological Markers; Cellular Immunity; Clinical Research; Clinical Trials; DNA; DNA Vaccines; Data; Development; Drug Formulations; Electroporation; Epitopes; Equilibrium; Future; Genes; Genetic; HIV; HIV vaccine; HIV-1; Human; Human Volunteers; Immune Sera; Immune response; Immunization; Injection of therapeutic agent; Intramuscular; Manuscripts; Measurable; Methods; Monitor; Needles; Oryctolagus cuniculus; Patients; Phase; Proteins; Publishing; QS21; Safety; Serum; System; Technology; Testing; Vaccines; Viral; Virus; Work; base; design; env Gene Products; immunogenic; immunogenicity; improved; neutralizing antibody; next generation; pre-clinical; preclinical study; programs; screening; vaccine development

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.

项目1将专注于使用下一代多价env HIV HIV疫苗配方的优化 多基因，多价DMA Prime-蛋白质增强技术平台。 我们的第一个HIV疫苗配方DP6-001是几年前开发的，用于概念证明试验 证明了人类志愿者中DMA Prime蛋白增强方法的免疫原性。这 从1990年代中期，从HIV感染患者中分离出的原发性ENV抗原被随机选择 他们的遗传进化枝。现在，艾滋病毒疫苗领域的快速进步为我们提供了更大的选择 主要的ENV抗原，尤其是过去研究的进化枝中的Env蛋白，那些Env 蛋白质具有有关病毒分离的患者的更多详细信息。此外， 最近开发的假型中和分析和新建立的靶标HIV-1主要病毒 面板（“层系统”）提供了可衡量的标准，以指导我们选择更相关的主要原理 ENV抗原用于开发艾滋病毒疫苗，重点是诱导中和抗体 回答。通过利用上述进度，我们已经确定了一组主要的ENV抗原 与我们以前的配方中所包含的抗体相比，能够引起更广泛的中和抗体 DP6-001。在本IPCAVD计划的当前项目1中，将进行以下研究： 目的1以最终选择下一代多价env配方，以进一步提高质量 中和抗体活性。 目标2选择免疫原性佐剂，以作为下一代蛋白质增强的一部分 多价env制剂。 AIM 3以测试DMA启动时下一代多价env制剂的免疫原性 通过电穿孔方法传递。 目标4以检查由DMA Prime蛋白增强方法引起的免疫血清中的表位谱 确定负责中和活动的抗体的表位特异性。