Cellular Responses

细胞反应

• 批准号: 9261464
• 负责人: DAVID B. WEINER
• 金额: $ 65.67万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9261464
• 关键词: ALVAC; Adjuvant; Antibodies; Antibody Response; Antigens; Benchmarking; CXCL13 gene; Clinic; Clinical; Collection; Consensus; DNA; DNA Vaccines; Development; Devices; Electroporation; Genes; Genetic; Goals; HIV; HIV Envelope Protein gp120; HIV Vaccine Trials Network; HIV vaccine; Immune; Immune response; Immunity; Immunization; Investigation; Light; Oryctolagus cuniculus; Plasmids; Polyvalence; Proteins; Scheme; Skin; Surface; T cell response; T-Lymphocyte; Technology; Testing; Vaccines; Variant; Viral Vector; arm; chemokine; clinical development; cytokine; design; gp160; improved; innovation; next generation; novel; programs; response; simian human immunodeficiency virus; success; synthetic construct; vaccine trial; vector; vector vaccine

Project 1 Abstract An effective HIV vaccine remains an elusive goal. The possible limited success of the RV144 vaccine trial supports that it is possible to provide protection from HIV acquisition through immunization. However, the vaccine-induced responses elicited by the RV144 ALVAC vCP1521-AIDSVAX B/E strategy were modest and of limited durability. The immune responses induced in a preferred vaccine should be superior to those observed in RV-144 (low T cells, limted antibodies, partially effective) as well as STEP and HVTN 505 (limited antibody responses, non effective T cell responses). A vaccine platform that avoids induction of anti-vector immunity is of growing importance in light of possible enhancement issues. Currently, there is no such HIV vaccine available, and few groups have the combination of technologies proven in the clinic to produce such a platform. This innovative program makes major advances in new DNA adaptive EP + gene adjvuant vaccine technology which in the clinic generates T cell immunity equivalent or superior to live viral vector vaccines (30, 2). We will build on this recent clinical success by novel genetic adjuvants focused on improved antibody induction as well as next generation adaptive EP focusing on skin delivery. We concentrate on increasing the breadth of coverage induced by these designed DNA vaccine by exploring the potential of a multivalent DNA prime followed by a multivalent protein boost. Furthermore, we plan to develop this collection of technologies in a simplified vaccine scheme that has distinct clinical advantages for global testing. There are three aims that comprise this program.

项目1摘要 有效的艾滋病毒疫苗仍然是一个难以捉摸的目标。 RV144疫苗试验可能有限的成功 支持可以通过免疫提供保护免受艾滋病毒的保护。但是， RV144 ALVAC VCP1521-AIDSVAX B/E策略引起的疫苗诱导的反应是适度的，并且是 有限的耐用性。首选疫苗中诱导的免疫反应应优于在 RV-144（低T细胞，Lim抗体，部分有效）以及步骤和HVTN 505（有限的抗体 响应，无效的T细胞反应）。避免诱导抗媒介免疫的疫苗平台是 鉴于可能的增强问题，越来越重要。目前，没有这样的艾滋病毒疫苗， 很少有小组在诊所中证明了这种平台的诊所中证明的技术结合在一起。这 创新计划在新的DNA自适应EP +基因相邻疫苗技术方面取得了重大进展 在诊所中，T细胞免疫等效或优于活病毒载体疫苗（30，2）。我们将建造 在新型遗传佐剂的最新临床成功中，重点是改善抗体诱导，下一步 一代自适应EP专注于皮肤输送。我们专注于增加覆盖范围的广度 通过这些设计的DNA疫苗，通过探索多价DNA Prime的潜力，然后是多价 蛋白质提升。此外，我们计划在简化的疫苗方案中开发这种技术集合 在全球测试方面具有明显的临床优势。有三个构成该程序的目标。