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总结 项目 3 主要关注此 IPCAVD 提案的产品生产方面（具体目标 1）。这是 由领先的 HIV 疫苗开发组织——Inovio Pharmaceuticals (INO) 指导，该组织在 多个临床 DNA 疫苗项目。 Inovio 在合成 DNA 开发方面拥有丰富的专业知识 疫苗和先进的体内电穿孔递送。项目3的中心目标是cGMP生产 并在该计划的第 4 年和第 5 年提供 2 个 DNA 免疫原构建体的产品。使用 Inovio 的先进技术 工艺技术经验丰富的团队将管理生产具有特定状态的产品的 CMC 方面 用于原料药和药品生产活动的最先进的生产设施，可生产瓶装剂量，以及 支持在该计划的第 5 年提交 IND 提交。此外，Inovio 将支持使用 下一代紧凑型、便携式、手持式皮内 EP 输送装置 CELLECTRA™ 3PSP。这 整个过程中将提供并用于所有动物模型的临床前研究 程序。 3PSP 将支持 HVTN 启动的后续临床试验。在 具体目标2 项目3将与项目1合作评估和推进双抗原的开发 和细胞因子 DNA 构建体。我们对双启动子 IL-12 构建体的开发工作将提供 这些双启动子构建体的蓝图将表达 HIV 抗原和细胞因子佐剂。项目3将 在整个项目期间提供 NHP 研究的协调和支持，其中包括 免疫原性和 IND 支持研究，以推进源自以下来源的 HIV 疫苗结构的开发 项目 1 和 2。在具体目标 3 中，我们将评估采用变革性皮肤递送的 DNA 疫苗递送 临床相关模型（包括豚鼠和 NHP）中的方案，将无针喷射输送与 皮肤电穿孔。综上所述，项目3将为后续提供高质量的浓缩制剂。 HVTN 临床测试并推进新型 HIV DNA 疫苗结构和递送平台的开发。