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主要关注IPCAVD提案的产品生产方面（具体目标1）。是 由领先的HIV疫苗开发组织- Inovio Pharmaceuticals（INO）指导， 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种DNA免疫原构建体的产品。使用Inovio先进的 工艺技术，经验丰富的团队将管理CMC方面的生产产品的具体状态， 用于生产瓶装剂量的原料药和制剂活动的最先进生产设施，以及 支持在项目第5年提交IND申请。此外，Inovio将支持使用 下一代紧凑、便携、手持式皮内EP输送装置，CELLECTRA™ 3 PSP。这 将提供器械并用于整个研究期间所有动物模型的临床前研究。 程序. 3 PSP将用于支持HVTN发起的后续临床试验。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。我们的双启动子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 在整个项目期间为国家卫生政策研究提供协调和支持，包括 免疫原性和IND使能研究，以推进开发HIV疫苗构建体， 项目1和2。在具体目标3中，我们将评估采用转化皮肤递送的DNA疫苗递送 临床相关模型中的方案，包括豚鼠和NHP，将无针喷射输送与 皮肤电穿孔综上所述，项目3将为后续项目提供高质量的浓缩制剂。 HVTN的临床测试和推进新的HIV DNA疫苗构建和交付平台的发展。