CONTROLLED DELIVERY SYSTEM FOR ANTHRAX VACCINE

炭疽是美国最严重的传染病之一， 在外国领土上的军事人员。虽然多个 大剂量的灭活疫苗和抗生素已被用于 炭疽病的预防和治疗，分别有 是一个明确的需要更有效的，单次（或最大限度的 二）免疫缓释制剂 保护 这一点，以及相对安全的可用性 重组保护性抗原（r-PA）形式的疫苗作为 可注射的，可吸收的凝胶形成剂，提供了追求 建议方案。 因此，第一阶段的目标是确定 使用新型、可注射、可吸收凝胶形成的可行性 共聚酯作为载体用于控制释放系统的开发 的R-。 第一阶段计划包括（1）合成和表征 （2）候选r-PA制剂的制备 （包括加入凝胶形成剂，以及加入和不加入阳离子- 交换剂和微囊化）和对照r-PA/明矾，用于 通过皮下注射免疫小鼠;和（3）测定 抗体应答。 将使用I期研究的结果 设计II期计划，包括（1） 动物模型;（2）一种制剂的开发和放大研究; 以及（3）完成安全性研究的主要部分。 建议的商业应用 第一阶段成功的主要结果是证明了 使用可吸收的凝胶形成组合物来开发 炭疽疫苗的有效、受控的输送系统， 获得计划II期研究的基础数据。 最终发展 作为一次性疫苗， 在预防炭疽病方面， 为平民和军事人员提供商业产品。

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. PROPOSED COMMERCIAL APPLICATION 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.