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.