Diarrhea is a major cause of morbidity and mortality in developing countries, especially in infants and young children. Enterotoxigenic E. coli (ETEC) cause a significant proportion of this disease, as well as episodes of acute diarrhea experienced by travelers to less developed countries. ALL ETEC strains produce heat-labile toxin (LT), heat stable toxin (ST), or both. The importance of LT and ST neutralizing antibodies and stimulation of secretory immunity in the prevention of diarrheal disease is well documented. Thus, an effective vaccine against ETEC will contain immunogenic, nontoxic forms of LT and ST. We propose to construct strains of attenuated Salmonella expressing LT-B/ST fusion proteins capable of eliciting an antitoxin secretory immune response. The results of this work will be used to assess the potential for manufacturing and commercializing an efficacious, multivalent vaccine for ETEC. If the approach is successful, additional protective epitopes from ETEC strains and other diarrheal pathogens could be added.
