Novel oral delivery system for subunit vaccine against ETEC

项目摘要/摘要 口服疫苗有可能革命性地改善中国人的生活质量 发展中国家。因为这些疫苗可以由社区卫生工作者接种 谁不是训练有素的医务人员，能在短时间内接种疫苗的人数 时间大大增加，而每名患者的成本显著降低。口头的 疫苗还避免了受污染的注射器和针头的危险，这是对 艾滋病毒和肝炎发病率高的地区。更广泛使用口服疫苗的一个障碍是 传染性疾病是大多数疫苗在通过严酷的酸性物质时被销毁。 胃的环境，在那里它们被蛋白水解酶降解。这样做的目的是 研究项目是开发一种新的口服疫苗递送系统来保护疫苗 当蛋白质通过胃和肠腔时。这种疫苗针对的是 产肠毒素大肠杆菌(ETEC)，南亚儿童死亡的主要原因 和撒哈拉以南非洲地区。ETEC感染也是导致游客和 前往发展中国家的军事人员。目前还没有获得疫苗许可的疫苗 ETEC的预防。这项第一阶段SBIR研究项目旨在保护ETEC疫苗 微珠中的蛋白质保持密封，直到它们与壁直接接触 在小肠上。只有到那时，被包裹的蛋白质才会从载体中释放出来。作为一名 结果，疫苗蛋白质不会被蛋白酶破坏，直到它们接近 靠近Peyer氏斑的M细胞。这应该会大大提高一次 疫苗将被M细胞吸收，并传递给粘膜免疫细胞。建立 证明了本系统的概念，我们将追求三个具体目标：1)优化性能 微球在a)它们对被包裹的蛋白质抗原的保护作用方面 蛋白水解酶和b)与刷状边缘酶接触时抗原的释放；2)负载 具有限定数量的选定ETEC抗原和已建立的佐剂的微球； 3)检测负载微珠在小鼠体内诱导免疫反应的能力 通过灌胃给药。传递系统的一个重要特征是它基于 马铃薯淀粉的天然分解产物。这增加了该系统可能被 以适中的成本扩大规模，可以为广泛接种提供可行的选择 在资源匮乏的社区。

Project Summary/Abstract Oral vaccines have the potential to make a revolutionary improvement in the quality of life in developing countries. Since these vaccines can be administered by community health workers who are not trained medical personnel, the number of people who can be immunized in a short period of time is drastically increased while the cost per patient is significantly lowered. Oral vaccines also avoid the danger of contaminated syringes and needles which is a serious threat in areas with high rates of HIV and hepatitis. One obstacle to the wider use of oral vaccines against infectious diseases is that most vaccines are destroyed as they pass through the harsh acidic environment of the stomach where they are degraded by proteolytic enzymes. The goal of this research project is to develop a new delivery system for oral vaccines that protects the vaccine proteins as they pass through the stomach and the lumen of the intestine. This vaccine targets enterotoxogenic E. coli (ETEC), a major cause of death in young children living in South Asia and Sub-Saharan Africa. ETEC infections are also the major cause of diarrhea in tourists and military personnel travelling to the developing world. No vaccine has been licensed for the prevention of ETEC. This Phase I SBIR research project is designed to shield the ETEC vaccine proteins within microbeads that remain sealed until they come into direct contact with the wall of the small intestine. Only then are the encapsulated proteins released from the carriers. As a result, the vaccine proteins are shielded from destruction by proteases until they are in close proximity to the M cells of the Peyer’s patches. This should greatly improve the odds that a vaccine will be taken up by the M cells and be passed on to mucosal immune cells. To establish proof of concept of this system, we will pursue three specific aims: 1) Optimize the performance of the microbeads in terms of a) their protection of encapsulated protein antigens from proteases and b) the release of the antigens upon contact with brush border enzymes; 2) Load the microbeads with defined amounts of selected ETEC antigens and an established adjuvant; and 3) Test the ability of the loaded microbeads to induce immune responses in mice when administered by gavage. An important feature of the delivery system is that it is based on a natural breakdown product of potato starch. This raises the possibility that the system can be scaled up at modest cost and that it can provide a feasible option for widespread immunization in resource-poor communities.