A new, rapidly dissolving and thermally stable dry powder Hepatitis-B vaccine

描述(由申请人提供)：该项目的首要目标是将一种新型干粉乙肝疫苗推向商业化的道路。在第一阶段的SBIR中，我们在体外测试了三种商用Shanvac-B的Hep-B干粉制剂，并在-20℃到65℃的温度范围内展示了粉末的稳定性和免疫原性。在这些极端温度下，由于乙肝表面抗原与明胶佐剂分离，目前市场上的液体乙肝疫苗被灭活。我们的研究还表明，干燥的微米级粉末溶解非常快，这表明它们在针对非肠道给药的单剂量自动重建装置中具有应用价值。这些结果对疫苗的储存、运输和管理具有深远的影响，特别是在 在发展中国家，有限的制冷和电力以及较高的环境温度限制了液体疫苗的使用寿命和效力。在拟议的第二阶段SBIR研究中，我们将从我们之前开发的三个配方中选择“最佳”配方，并将该粉末与Becton Dickinson(BD)正在开发的单剂量自动重建设备配对。药物-装置组合将用于评估小鼠模型的效力，并与将通过针头和注射器给药的对照组动物进行比较。效价将通过动物血清的酶联免疫吸附分析进行评估。。第二阶段工作的结果将根据HEP-B干粉配方的效力以及BD设备的功能和性能与针头和注射器给药的效力进行比较来判断。

DESCRIPTION (provided by applicant): The overarching goal of this project is to move a new, dry powder formulation of Hepatitis-B vaccine on its path to commercialization. In the Phase I SBIR we tested in vitro three Hep-B dry powder formulations of commercially available Shanvac-B and demonstrated powder stability and immunogenicity at temperatures ranging from -20 ?C through 65 oC. At these temperature extremes the currently marketed liquid Hepatis B vaccine is inactivated as the HBsAg antigen separates from the alum adjuvant. Our studies also showed that the dry micro-scale powders dissolved very rapidly, suggesting their utility in single dose auto-reconstitution devices aimed at parenteral administration. These results have far-reaching implications in regard to vaccine storage, transport and administration, especially in developing countries where limited refrigeration and electric power and high ambient temperatures restrict the useful life and potency of liquid vaccines. In the proposed Phase II SBIR study, we will choose the "optimum" formulation from the three that we developed earlier and pair this powder with a single dose auto-reconstitution device being developed by Becton Dickinson (BD). The drug- device combination will be used to assess potency in a mouse model compared to a control group of animals that will be administered Shanvac-B by needle and syringe. Potency will be assessed from ELISA analysis of animal sera. . The outcome of the Phase II work will be judged based on the potency of the Hep-B dry powder formulation and the functionality and performance of the BD device as compared with the potency of the needle and syringe administration.