Novel Delivery Systems for Nasal Administration of Anthrax Vaccine

Sheena Hailin Wang: Novel Delivery Systems for Nasal Administration of Anthrax Vaccine (Under the direction of Dr. Anthony J. Hickey, Ph.D., D.Sc.) There is current biodefense interest in protection against Anthrax. The inhaled form of anthrax is difficult to diagnose and can be fatal without prompt antibiotic intervention. Prophylactic vaccination has become a critical measure for protection of individuals at risk of exposure. This thesis makes the efforts to develop a new generation of stable, effective and affordable anthrax vaccine. This project studies the immune response elicited by rPA with a mast cell activator, Compound 48/80 as adjuvant. The vaccine formulation was prepared in a dry powder form by spray-freeze-drying (SFD) under optimized conditions to produce particles with a target size of 25μm median diameter, suitable for rabbit nasal delivery. Physicochemical properties of the powder vaccines were characterized in order to assess the powder delivery and storage potentials. Structural stability of PA after the SFD process and storage were confirmed by two spectroscopic techniques (CD and ATR-FTIR), while functional stability of both the antigen and adjuvant were monitored via cell-based assays. Animal studies were performed to evaluate the in vivo efficacy of the powder vaccines in rabbits using a Unitdose powder device. Results showed that C48/80 is an effective mucosal adjuvant in rabbits. SFD powder formulations freshly prepared or stored for over two years at room temperature were able to elicit a significant serum anti-body and functional titer comparable to IM injection.