Project establishment: Development of vaccine(s) against infections with diarrheagenic Escherichia coli and Shigella

Diarrheal diseases are the second most common cause of death in children, accounting for 1/5 of the 10.6 million annual child deaths. In addition, repeated episodes of diarrhea, especially if prolonged and associated with growth faltering, are an importan t cause of malnutrition in developing countries. Rotavirus, enterotoxigenic E. coli (ETEC), enteroaggregative E. coli (EAEC), Shigella spp. and Cryptosporidium spp. are among the biggest killers. Despite several years' of intensive research, the develo pment of vaccines against the most important bacterial diarrheal pathogens has yet to achieve the same success. A recent meta-analysis demonstrates the importance of enteroaggegative E. coli (EAEC) in acute and persistent diarrhea, the latter being an imp ortant cause of malnutrition and death. We will undertake research and development towards developing a multivalent vaccine or a few vaccines which can be delivered together with the current childhood vaccines and which would substantially reduce the b urden of diarrheal disease and malnutrition in Indian and other developing country children. The vaccine(s) will consist of important antigens from the most pathogenic subtypes of ETEC, EAEC and other diarrheagenic E. coli, as well as Shigella spp. Bef ore embarking on a strategy to develop the(se) vaccine(s), extensive interaction between the consortium members and others will take place. Moreover, the Department of Vaccines and Biologicals at the WHO will convene a meeting, for which we hereby seek su pport. This meeting will be important for developing a proposal for the GLOBVAC program, the corresponding and linked program administered by the Department of Biotechnology in India as well as the new Bill and Melinda Gates Foundation initiative for ETEC and Shigella vaccine development. The proposal will be submitted to RCN-DBT by the deadline scheduled for June 2007, and the project will, if funded, then be initiated in January 2008.