BIOELASTIC NANOPARTICLES FOR DELIVERY OF VACCINES

描述：（申请人提供）本研究的总体目标 目前的努力是开发用于递送疫苗的生物弹性纳米颗粒。的 纳米颗粒同时作为佐剂和作为受控的 一种释放装置，其能够通过单次给药实现主要和 随后通过立即和持续释放抗原进行免疫。的 破伤风毒素的C-片段Tox-C将是模型抗原，因为其 固有免疫原性低，pI为5.1，在免疫治疗中的重要性 世界性破伤风健康问题。 第一阶段提案的具体目标是： 1)利用重组蛋白设计并制备四种弹性蛋白聚合物 DNA技术构建基因，E. coli转化表达， 通过发酵和纯化生产。 2)为了制备由四种纳米颗粒组成的生物弹性纳米颗粒（200 nm或更小）， 聚合物 3)用破伤风毒素的C片段（Tox-C）负载纳米颗粒。 4)确定纳米颗粒的体外Tox-C释放曲线， 5)为了评价使用具有优选释放的两种组合物在小鼠中的功效， 特征和佐剂性。 不同疫苗抗原和给药途径的进一步评价， 体内动物模型研究的方法和临床研究的必要步骤 试验将在第二阶段进行。 拟议商业应用：不可用

DESCRIPTION: (Provided by Applicant) The overall objective of this research effort is to develop bioelastic nanoparticles for the delivery of vaccines. The nanoparticle is to function simultaneously as adjuvant and as a controlled release device capable, with a single administration, of achieving primary and follow on immunization by both immediate and sustained release of antigen. The C-fragment of tetanus toxin, Tox-C, will be the model antigen because of its low inherent immunogenicity, its pI of 5.1, and its importance in the world-wide tetanus health problem. The specific aims of this Phase I proposal are: 1) To design and prepare four elastic protein-based polymers using recombinant DNA technology for gene construction, E. coli transformation and expression, production by fermentation and purification. 2) To prepare bioelastic nanoparticles (200 nm or less) comprised of the four polymers. 3) To load the nanoparticles with the C-fragment of tetanus toxin (Tox-C). 4) To determine in vitro Tox-C release profiles for the nanoparticles, and 5) To evaluate efficacy in mice using two compositions with preferred release profiles and adjuvanticity. Further evaluation of different vaccine antigens and administration routes by means of in vivo animal model studies and the necessary steps toward clinical trials will be carried out during Phase II. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE