Novel oral delivery system for subunit vaccine against ETEC

点击翻译按钮获取中文摘要

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.