Transdermal vaccine delivery platform technology

透皮疫苗递送平台技术

• 批准号: 6774645
• 负责人: SEAJIN OH
• 金额: $ 32.35万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6774645
• 关键词: Langerhans' cell; active immunization; antibody titering; bioterrorism /chemical warfare; cellular immunity; cytotoxic T lymphocyte; human tissue; influenza vaccines; laboratory mouse; leukocyte activation /transformation; postmortem; public health; skin absorption; technology /technique development; transdermal drug delivery; vaccines

DESCRIPTION (provided by applicant): Responding to the concern that various viruses, bacteria, and bacterial toxins could be used as bioterrorist weapons, we are proposing to develop a transdermal vaccine delivery platform that can be administered by untrained end users in any place and at any time to protect civilian as well as military populations. The proposed vaccine delivery method will be needle-free, minimally invasive, inexpensive, easy to store and transport, and better tolerated by the human body. Most importantly, it will provide enhanced immunogenicity. While humoral immunity is essential for the control of extracellular pathogens, cell-mediated immunity is vital for host defense against intracellular pathogens, including viruses. Cell-mediated immunity, associated with the activation of CD8 cytotoxic T lymphocytes, is effectively administered through the pathway involving a special subpopulation of antigen-presenting cells, such as Langerhans cells (LCs). The epidermal layer of human skin, about 20 mu/m below the skin surface and about 100-200 (m thick, is highly immunoreactive because it contains abundant Langerhans cells, and is therefore an ideal target for vaccine injection. However, because the epidermal layer is thin and near the skin surface, it is difficult to inject target vaccine into the epidermal layer with the conventional needle injection method. Our strategy is to use a microneedle array, each needle about 300 pm in length, to perforate the stratum corneum and deliver vaccine in proximity to Langerhans cells in the epidermis. We hypothesize that the micro-needle vaccine injection may deliver vaccines to the cytosol of the Langerhans cells and induce a cytotoxic T lymphocyte response. Specific aims of this R21 study are to (1) develop an influenza vaccine micro-needle array and (2) evaluate vaccine delivery in mouse models.

描述（由申请人提供）：针对各种病毒、细菌和细菌毒素可能被用作生物恐怖武器的担忧，我们提议开发一种透皮疫苗输送平台，可由未经培训的最终用户在任何地点和地点进行管理。随时保护平民和军人。所提出的疫苗输送方法将是无针、微创、廉价、易于储存和运输，并且人体耐受性更好。最重要的是，它将提供增强的免疫原性。 虽然体液免疫对于控制细胞外病原体至关重要，但细胞介导的免疫对于宿主防御细胞内病原体（包括病毒）至关重要。细胞介导的免疫与 CD8 细胞毒性 T 淋巴细胞的激活相关，通过涉及抗原呈递细胞的特殊亚群（例如朗格汉斯细胞 (LC)）的途径有效地进行。人体皮肤的表皮层位于皮肤表面以下约20μ/m，厚约100-200μm，由于含有丰富的朗格汉斯细胞，因此具有高度免疫反应性，因此是疫苗注射的理想目标。由于表皮层薄且靠近皮肤表面，用传统的针头注射方法很难将目标疫苗注射到表皮层，我们的策略是使用微针阵列，每针约300 pm。我们假设微针疫苗注射可以将疫苗递送至朗格汉斯细胞的细胞质并诱导细胞毒性T淋巴细胞反应。 这项 R21 研究的具体目标是 (1) 开发流感疫苗微针阵列和 (2) 评估小鼠模型中的疫苗递送。