SBIR-STTR Award

Adenoviruses are a frequent cause of epidemic acute respiratory disease (ARD) in military recruit training centers and pose a significant threat to military readiness, especially during times of large mobilization. There are no FDA-licensed treatment options available for adenovirus infections. The objective of this proposal is to re-develop Ad4 and Ad7 live viral vaccines which will 1) modernize commercial scale production, 2) reduce cold chain vaccine distribution and storage logistics, and 3) develop a production platform that can be readily applied to other adenovirus serotype vaccine candidates. In this proposal, we will develop Ad4 and Ad7 live, oral delivery vaccines comparable to the existing FDA-licensed vaccines, but using modernized Ad4 platform technologies that are currently in use or in development at PaxVax, including: ? Novel A549 cell substrate: A549 continuous cell line to enable large-scale bulk adenovirus production using serum free medium in disposable, closed bioreactor; ? Thermostable formulation: room temperature stable formulation compatible with both freeze drying and spray drying process technologies; ? Spray-drying: replace the lyophilization process with a spray-drying process to improve control and product consistency; ? Oral capsule dosage form: use of modern aqueous enteric coating material to manufacture oral dosage capsules as final drug product.

Adenoviruses are a frequent cause of epidemic acute respiratory disease (ARD) in military recruit training centers and pose a significant threat to military readiness, especially during times of large mobilization. There are no FDA-licensed treatment options available for adenovirus infections. Under the SBIR phase I, PaxVax successfully re-developed research-grade Ad4 and Ad7 capsule vaccines with comparable potency to the Teva Ad4 and Ad7 Tablet vaccines using modernized platform technologies, including a high-yield continuous cell line, serum-free medium, single-use bioreactor and purification technologies, new thermostable formulations and aqueous enteric-coating. During the SBIR Phase II, PaxVax will cGMP manufacture clinical Ad4/Ad7 vaccines with processes and assays developed under the SBIR I. PaxVax will produce Ad4/Ad7 cGMP master viral seeds (MVS) with plaque-purified and amplified pre-MVS, bulk drug substances (BDS), and final drug products (FDP), and subsequently release these products for clinical trials. The produced Ad4/Ad7 FDP will also be placed on a stability program as required to support the trials. A small clinical trial will be conducted to evaluate the safety and immunogenicity of a single dose of the PaxVax Ad4/Ad7 vaccines. A successful clinical trial will in turn advance the production processes to a commercial production stage.