Anthrax is among the most serious infections encountered in the United States and by military personnel on foreign soil. Although multiple doses of killed vaccine and antibiotics have been used in the prophylactic and therapeutic treatments of anthrax, respectively, there is a definite need for a more efficacious, single-shot (or maximum of two) controlled release formulation for immunization and prolonged protection. This, and the availability of the relatively safe recombinant protective antigen, (r-PA) form of the vaccine as the injectable, absorbable gel-formers, provided an incentive to pursue the proposed program. Thus, the objective of Phase I is to determine feasibility of using novel, injectable, absorbable gel-foming copolyesters as carriers for development of a controlled release system of r-. And, Phase I plans entail (1) synthesis and characterization of the polymeric carrier; (2) preparation of candidate r-PA formulations (including incorporation in gel-formers and with and without cation- exchangers and microencapsulation) and a control r-PA/alum for use in immunizing mice by subcutaneous injection; and (3) determination of the antibody response using ELISA. Results of Phase I study will be used to design Phase II plans, which will include (1) efficacy study in animal models; (2) development and scale-up study of one formulation; and (3) completing major segments of the safety study.
Primary outcome of a successful Phase I is demonstrating the feasibility of using an absorbable gel-forming composition for development of an efficacious, controlled delivery system of an anthrax vaccine and obtaining basic data for planning Phase II study. Eventual development of this system as a one-shot vaccine will represent a major achievement in the protection against anthrax and is expected to yield successful commercial products for the civilian population and military personnel.
