Vaccine and adjuvant Clinical GMP product development and DNA Technology platform enhancements

疫苗和佐剂临床 GMP 产品开发和 DNA 技术平台增强

• 批准号: 10589589
• 负责人: Trevor Smith
• 金额: $ 118.01万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-08 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589589
• 关键词: Adjuvant; Advanced Development; Animal Model; Animals; Antigens; Asia; Cavia; Charge; Clinical; Clinical Research; Clinical Trials; Collaborations; Coupled; Cyclic GMP; DNA; DNA Vaccines; Dedications; Development; Devices; Dose; Drug Delivery Systems; Electroporation; Europe; Evaluation; Goals; Guidelines; HIV; HIV Antigens; HIV Vaccine Trials Network; HIV vaccine; Human; Immune response; Interleukin-12; International; Intramuscular; Mediating; Modeling; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plasmids; Process; Production; Program Development; Protocols documentation; Research; Research Support; Running; Skin; Technology; Vaccines; Vial device; Work; clinically relevant; cytokine; design; experience; immunogenicity; in vivo; manufacture; manufacturing facility; minimally invasive; next generation; novel; phase 3 study; plasmid DNA; portability; preclinical development; preclinical study; product development; programs; promoter; research clinical testing; scale up; synergism; synthetic construct; technology platform; vaccine delivery; vaccine development

Project 3 Summary Project 3 is primarily focused on the product production aspects of this IPCAVD proposal (Specific Aim 1). It is directed by a leading HIV vaccine development organization – Inovio Pharmaceuticals (INO) who have advanced multiple clinical DNA vaccine programs. Inovio has extensive expertise in development of synthetic DNA vaccines and advanced in vivo electroporation delivery. The central goal of Project 3 is to cGMP manufacture and deliver product for 2 DNA immunogen constructs in years 4 and 5 of the program. Using Inovio’s advanced process technology the experienced team will manage CMC aspects of producing product with specific state-of- the-art manufacturing facilities for drug substance and drug product activities resulting in vialed doses, and support IND submission to be delivered in year 5 of the program. Additionally, Inovio will support the use of the next generational compact, portable, hand-held intradermal EP delivery device, CELLECTRA™ 3PSP. This device will be provided and employed for the preclinical studies across all animal models throughout this program. 3PSP will be available to support the subsequent clinical trials which will be initiated by the HVTN. In Specific Aim 2 Project 3 will collaborate with Project 1 to evaluate and advance the development of dual antigen and cytokine DNA constructs. Our development work with the dual promoter IL-12 constructs, will provide the blueprint for these dual promoter constructs that will express a HIV antigen and cytokine adjuvant. Project 3 will provide coordination and support of the NHP studies throughout the duration of the project which will include immunogenicity and IND-enabling studies to advance the development HIV vaccine constructs originating from Project 1 and 2. In Specific Aim 3, we will evaluate DNA vaccine delivery employing transformative skin delivery protocols in clinically relevant models, including guinea pigs and NHPs, integrating needleless jet delivery with skin electroporation. In summary, Project 3 will provide high quality concentrated drug product for subsequent HVTN clinical testing and advance the development of novel HIV DNA vaccine constructs and delivery platforms.

项目3摘要 项目3主要侧重于IPCAVD提案的产品生产方面(具体目标1)。它是 由领先的艾滋病毒疫苗开发组织-Inovio制药公司(INO)指导，他们已经取得了进展 多种临床DNA疫苗计划。Inovio在合成DNA的开发方面拥有丰富的专业知识 疫苗和先进的体内电穿孔传递。项目3的中心目标是cGMP制造 并在计划的第4年和第5年交付2个DNA免疫原构建的产品。使用Inovio的高级 工艺技术经验丰富的团队将管理CMC方面的生产特定状态的产品- 用于生产瓶装剂量的药物物质和药物制品活动的最先进的制造设施，以及 支持在计划的第5年提交IND。此外，Inovio将支持使用 下一代紧凑型便携式手持式EP皮内给药装置CELLECTRA™3PSP。这 将提供设备并将其用于所有动物模型的临床前研究 程序。3PSP将可用于支持由HVTN启动的后续临床试验。在……里面 特殊目标2项目3将与项目1合作评估和推进双重抗原的开发 和细胞因子DNA构建。我们的双启动子IL-12构建的开发工作，将提供 这些双启动子构建的蓝图将表达HIV抗原和细胞因子佐剂。项目3将 在整个项目期间协调和支持国家惠普研究，包括 免疫原性和IND使能研究推进源于以下来源的HIV疫苗构造的开发 项目1和2。在具体目标3中，我们将使用变革性皮肤递送来评估DNA疫苗递送 在包括豚鼠和NHP在内的临床相关模型中的方案，将无针喷射分娩与 皮肤电穿孔。综上所述，项目3将为后续提供高质量的浓缩药物产品 HVTN临床试验和推进新型HIV DNA疫苗构建和递送平台的开发。