TRANSCUTANEOUS IMMUNIZATION FOR DNA

DNA 经皮免疫

• 批准号: 6017931
• 负责人: GREGORY M GLENN
• 金额: $ 10万
• 依托单位: IOMAI CORPORATION
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6017931
• 关键词: Orthomyxoviridae; capsid; cellular immunity; dendritic cells; drug vehicle; green fluorescent proteins; immunomodulators; laboratory mouse; plasmids; polyethylenes; simian virus 40; transdermal drug delivery; vector vaccine; virus protein

The objective of this proposal is to evaluate the potential for delivering DNA vaccines via transcutaneous immunization technology (TCI). The potential advantages for combining DNA vaccine and TCI technologies are related to the ability of DNA vaccines to elicit the production of cytotoxic T lymphocytes and humoral responses recognizing conformational determinants. The likelihood of success for DNA vaccination via TCI is significant since preliminary data show that antigens the size of virus particles are immunogenic in this approach. We will examine the feasibility of delivering DNA vaccine vectors that are condensed into small, nuclease resistant particles, or packaged into non- enveloped virus capsid coats. Using green fluorescent protein expression as a readout, conditions will be developed to optimize transcutaneous delivery of polyethylenimine-condensed DNA into epidermal dendritic cells. The effects of various TCI adjuvants on delivery will also be examined. To optimize the induction of humoral and CTL responses via DNA TCI, a vector encoding influenza virus nucleoprotein will be employed. Finally, we will also encapsulate DNA vaccines into SV4O virus capsid coats due to the demonstrated ability of such particles to protect DNA from nuclease attach and efficiently deliver plasmids into the nucleus of mammalian cells in vivo and in vitro. PROPOSED COMMERCIAL APPLICATIONS: The development of a Transcutaneous tetanus booster could decrease the risk of immunization- related needle sticks and associated needle-borne disease, increase compliance with immunization protocols, improve access to vaccination by eliminating the need for trained personnel and sterile equipment to achieve immunization and reduce the complications related to physical skin penetration in successful immunization. Efficient delivery of DNA for vaccination could open the use of this strategy for a number of vaccines where it is presumed that DNA immunization is advantageous.

本提案的目的是评估通过经皮免疫技术（TCI）提供DNA疫苗的潜力。结合DNA疫苗和TCI技术的潜在优势与DNA疫苗引起细胞毒性T淋巴细胞产生和识别构象决定簇的体液应答的能力有关。通过TCI进行DNA疫苗接种成功的可能性很大，因为初步数据显示，病毒颗粒大小的抗原在这种方法中具有免疫原性。我们将研究递送DNA疫苗载体的可行性，所述载体浓缩成小的、核酸酶抗性颗粒，或包装成无包膜病毒衣壳。使用绿色荧光蛋白表达作为读数，将开发条件以优化聚乙烯亚胺缩合的DNA经皮递送到表皮树突状细胞中。还将检查各种TCI佐剂对递送的影响。为了优化通过DNA TCI诱导体液和CTL应答，将使用编码流感病毒核蛋白的载体。最后，我们还将将DNA疫苗封装到SV4O病毒衣壳外壳中，这是由于已证明这种颗粒能够保护DNA免受核酸酶附着并在体内和体外有效地将质粒递送到哺乳动物细胞的细胞核中。拟议的商业应用：开发经皮破伤风加强剂可以减少与免疫有关的针刺和相关的针媒疾病的风险，提高对免疫规程的遵守，通过消除对经过培训的人员和无菌设备的需求来实现免疫，改善获得疫苗接种的机会，并减少成功免疫中与物理皮肤穿透有关的并发症。有效地递送DNA用于疫苗接种可以将这种策略用于许多疫苗，其中假定DNA免疫是有利的。