S50 nanocapsules for transcutaneous DNA vaccination

用于经皮 DNA 疫苗接种的 S50 纳米胶囊

• 批准号: 6790964
• 负责人: GRETCHEN M UNGER
• 金额: $ 14.67万
• 依托单位: GENESEGUES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2006-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6790964
• 关键词: AIDS education /prevention; AIDS vaccines; aluminum; antigen presenting cell; antigens; beta galactosidase; biotechnology; cellular immunity; dendritic cells; dosage forms; drug delivery systems; drug design /synthesis /production; humoral immunity; hyaluronate; immune response; infant animal; longitudinal human study; microcapsule; nanomedicine; nanotechnology; nickel; organ culture; swine; topical drug application; vaccine development

DESCRIPTION (provided by applicant): The WHO estimates that 40 million individuals are infected with AIDS worldwide and that 16,000 new infections occur daily, lending continuing support for new approaches in vaccine technology. DNA vaccines offer the advantage over protein vaccines of improved cytotoxic T cells (CTL) responses by simulating infection by intracellular pathogens following effective transfection. Emerging evidence suggests, however, this transfection must be directed at dendritic cells (DC) and be coupled with significant maturation and migration of DCs. In the effort to develop an AIDS vaccine, early CTL responses rivaling natural infection have been achieved with DNA prime / viral boost protocols, but these responses have not persisted sufficiently in macaques to provide protection, suggesting the need for adjuvants or recombinant virus-like particles to provoke stronger initial T-cell responses. We have developed a sub-50 nm nanocapsule delivery vector, capable of caveolar uptake, that induces efficient transfection of large plasmids into activated, migrating Langerhans cells by passive topical application using an ex vivo porcine skin organ culture model. LCs, the dendritic cells of skin, are efficient for inducing a broad range of systemic and mucosal responses, but effective stimulation of migration has proven difficult in large animals by current transcutaneous methods. Due to anatomical similarities with humans, the porcine model is superior for evaluation of transcutaneous vaccines. In this pilot study, using the bacterial protein 13-galactosidse as a model antigen, we propose to prepare and test in organ culture and in weanling pigs, vaccine formulations comprised of hyaluronan and aluminum or nickel ion. Demonstration of improved cellular and humoral immune responses with decreased dosing will provide a strong foundation for follow-on studies in Rhesus macaques to improve mucosal immunity and T-cell responses against SIV.

描述（由申请人提供）：世卫组织估计，全世界有4 000万人感染艾滋病，每天有16 000人感染艾滋病，这为疫苗技术方面的新方法提供了持续支持。DNA疫苗通过模拟有效转染后细胞内病原体的感染，提供了优于蛋白质疫苗的改善细胞毒性T细胞（CTL）反应的优势。然而，新出现的证据表明，这种转染必须针对树突状细胞（DC），并伴随着树突状细胞的显著成熟和迁移。在开发艾滋病疫苗的过程中，已经通过DNA引物/病毒增强方案实现了与自然感染相抗衡的早期CTL反应，但这些反应在猕猴体内并没有持续足够的时间来提供保护，这表明需要佐剂或重组病毒样颗粒来激发更强的初始t细胞反应。