Development of Two-stage Multivaccine Delivery System with Protective and Bioadhesive Properties for Oral Immunization

"There is an ever increasing danger of biological warfare and bioterrorism. Among many agents, anthrax has been of prominence. The objective of this proposal is to develop Microsphere-based Delivery Systems ("MDS") for controlled and pulsed-release delivery of anthrax vaccine via single-dose oral immunization. The MDS will be designed and developed as follows:1. The recombinant protective antigen will be incorporated into biodegradable polymer microspheres to provide controlled and pulsed-release delivery of the anthrax vaccine equivalent to multiple immunizations.2. The antigen-encapsulated microspheres will be further coated with a bioadhesive polymer to promote the adhesion of the microparticles on to the mucosal membranes of the intestine.3. The above microspheres will be further coated with an enteric polymer to increase the protection of the antigen against the acidic pH of the stomach.4. A mucosal adjuvant will be incorporated into MDS to provide further potentiation of the immune system. The MDS products will be characterized and In Vitro release studies will be performed. Selected MDS products will be tested for their efficacy to induce antibody response in mice. In Option B, we will develop optimized MDS for immunization of rabbits which will be monitored for antibody response and shipped to USAMRIID for challenge with anthrax spores. The MDS is convenient, single-dose oral administration, and offers l