Liposome-Encapsulated Biodefense Vaccines

脂质体封装的生物防御疫苗

• 批准号: 7110534
• 负责人: LOUISE BRAUD LAWSON
• 金额: $ 4.6万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7110534
• 关键词: antigens; bioterrorism /chemical warfare; birth; communicable diseases; lipids; liposomes; skin

DESCRIPTION (provided by applicant): This objective of this investigation is to compare different liposome formulations for the ability to deliver vaccine antigens to the dendritic cells of the epidermis and initiate an effective immune response to target antigens following transcutaneous immunization. The choice of lipids used in liposome preparation should enhance penetration of the protein antigens through the stratum corneum into the epidermis, where immunologically-responsive cells exist. The first phase of the investigation will focus on uptake through the skin using an in vitro porcine model. Delivery of fluorescently-labeled liposomes and antigenic proteins to dendritic cells in the epidermis will be visualized as well. The second phase will determine the immunologic response, both serum and mucosal, to transcutaneously applied liposome-encapsulated Protective Antigen of Bacillus anthracis in a murine model. The immunogenicity of encapsulated versus free soluble protein will be compared. Lastly, the ability of a transcutaneously applied liposomal vaccine to protect immunized mice against an anthrax challenge will be assessed. Results will provide an understanding of influence of the lipid composition of liposomes on transport of proteins administered through the skin and the immunologic response to a transcutaneous liposomal vaccine, which could offer a new technique for protection against a number of infectious diseases.

描述（由申请人提供）：本研究的目的是比较不同脂质体制剂将疫苗抗原递送至表皮树突状细胞并在经皮免疫后启动针对目标抗原的有效免疫应答的能力。脂质体制备中使用的脂质的选择应增强蛋白质抗原穿过角质层进入表皮的渗透，其中存在免疫应答细胞。研究的第一阶段将重点关注使用体外猪模型通过皮肤的吸收。荧光标记的脂质体和抗原蛋白向表皮树突状细胞的递送也将被可视化。第二阶段将确定小鼠模型中经皮施用的炭疽杆菌脂质体封装的保护性抗原的免疫反应，包括血清和粘膜。将比较封装的可溶性蛋白与游离可溶性蛋白的免疫原性。最后，将评估经皮应用的脂质体疫苗保护免疫小鼠免受炭疽攻击的能力。结果将有助于了解脂质体的脂质成分对通过皮肤施用的蛋白质运输的影响以及对经皮脂质体疫苗的免疫反应，这可以提供一种预防多种传染病的新技术。