NEW LIPOSOME TECHNOLOGY FOR VACCINES

点击翻译按钮获取中文摘要

The long term goal of our project is to define the biochemical and immunological characteristics of a vaccine delivery system that will be stable to both environmental and biological effects, thus allowing for sustained and prolonged release of immunogens, maximal stimulation of the immune system, and protective immunity to pathogens. Liposomes prepared from phospholipids (PL) have been proposed to be a system that will enhance immunity to a wide variety of antigens, but they have not gained wide-use, presumably because of problems of cost and variable biochemical stability. We have data that suggests that a non-phospholipid liposome (NPL) made with a variety of single-tailed biodegradable amphiphiles solve these problems. Our hypothesis is that NPL will overcome the main disadvantage of PL's as carriers of antigens, namely lack of stability both in vitro and in vivo, but will have all of the previously documented advantages of PL in terms of delivery of immunogens and modulation of cells of the immune system. We are proposing to investigate in controlled studies in the mouse model, the immune system. We are proposing to investigate in controlled studies in the mouse model, the immune response to purified Hepatitis B (HB) antigens encapsulated in NPL. We will pursue 2 specific aims in this Phase I feasibility study to test: 1. Comparative studies on different chemical formulations of PL's and NPL's in terms of in vitro stability of NPL's. 2. The immunogenicity of HBsAg encapsulated in NPL's. Our studies are a prerequisite to Phase II studies that would test whether this system can be used for development of vaccines with extended stability that are effective in inducing protective long-term immunity to pathogens.