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

描述（由申请方提供）：本项目的总体目标是将一种新的乙肝疫苗干粉制剂推向商业化。在第一阶段SBIR中，我们在体外测试了三种市售Shanvac-B的Hep-B干粉制剂，并证明了粉末在-20 ℃至-25 ℃范围内的稳定性和免疫原性。C至65 oC。在这些温度极限下，目前市售的液体乙型肝炎B疫苗由于HBsAg抗原与明矾佐剂分离而失活。我们的研究还表明，干燥的微米级粉末溶解非常迅速，表明它们在单剂量自动重构装置中的实用性，目的是肠胃外给药。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高环境温度限制了液体疫苗的使用寿命和效力。在拟议的II期SBIR研究中，我们将从我们早期开发的三种制剂中选择“最佳”制剂，并将该粉末与Becton Dickinson（BD）开发的单剂量自动复溶装置配对。与通过针头和注射器给予Shanvac-B的对照组动物相比，药物-器械组合将用于评估小鼠模型中的效价。将通过动物血清的ELISA分析评估效价。.将根据Hep-B干粉制剂的效价以及BD装置的功能和性能（与针头和注射器给药的效价相比）判断II期工作的结果。

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.