Novel oral delivery system for subunit vaccine against ETEC

Project Summary Abstract Oral vaccines have the potential to make a revolutionary improvement in the quality of life in developing countriesSince these vaccines can be administered by community health workers who are not trained medical personnelthe number of people who can be immunized in a short period of time is drastically increased while the cost per patient is significantly loweredOral vaccines also avoid the danger of contaminated syringes and needles which is a serious threat in areas with high rates of HIV and hepatitisOne 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 enzymesThe 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 intestineThis vaccine targets enterotoxogenic EcoliETECa major cause of death in young children living in South Asia and Sub Saharan AfricaETEC infections are also the major cause of diarrhea in tourists and military personnel travelling to the developing worldNo vaccine has been licensed for the prevention of ETECThis 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 intestineOnly then are the encapsulated proteins released from the carriersAs a resultthe vaccine proteins are shielded from destruction by proteases until they are in close proximity to the M cells of the Peyer s patchesThis should greatly improve the odds that a vaccine will be taken up by the M cells and be passed on to mucosal immune cellsTo establish proof of concept of this systemwe will pursue three specific aimsOptimize the performance of the microbeads in terms of atheir protection of encapsulated protein antigens from proteases and bthe release of the antigens upon contact with brush border enzymesLoad the microbeads with defined amounts of selected ETEC antigens and an established adjuvantandTest the ability of the loaded microbeads to induce immune responses in mice when administered by gavageAn important feature of the delivery system is that it is based on a natural breakdown product of potato starchThis 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 Project Narrative Infectious diseases take nearlymillion human lives each yearmainly in AsiaAfricaand South AmericaOral vaccines offer the single greatest hope to improve this situation but in most cases these vaccines have not been as effective as injected vaccinesThis research project is designed to test a new strategy that could greatly improve the success of oral vaccines and could be of major benefit to millions of people in underdeveloped areas of the worldSpecificallythis project seeks to develop a relatively inexpensive oral vaccine against ETECa bacterial infection that each year kills thousands of children under the age ofin low income countries