Bacterial enteric infections and vaccine development

Abstract

There is a great need for effective vaccines against the major bacterial enteropathogens. Bacterial enteric infections resulting in diarrhea, dysentery, or enteric fever constitute a huge public health problem, with more than a billion episodes of disease and several million deaths annually in developing countries. Diarrhea caused by a bacterial enteric infection is also the commonest illness experienced by international travellers. Studies of pathogenesis have established the importance of specific ligand-receptor interactions between the enteropathogens and the intestinal epithelium, resulting in attachment and colonization of the bacteria and production of disease through either invasive mechanisms or production of toxins. Studies of protective immune mechanisms have emphasized the importance of secretory IgA antibodies and mucosal memory for protection against noninvasive, enterotoxigenic infections such as cholera and ETEC diarrhea and also drawn attention to the possible protective role of IFN-gamma production by intestinal T cells in these secretory diarrheas. In invasive dysenteric and enteric-fever infections caused by such organisms as Shigella and Salmonella, optimal protection may depend on a combination of mucosal and systemic immunity. On the basis of this knowledge, several new vaccines have been developed and proved to be efficacious in large field tests. These include an oral killed B-WC vaccine and a killed WC-alone vaccine against cholera, and both a live attenuated oral vaccine (Ty21a) and an injectable Vi antigen vaccine against typhoid fever. In addition, a killed oral ETEC vaccine and live attenuated oral Shigella vaccines have begun to be tested in phase 1 and phase 2 studies in humans. The properties of the new vaccines against bacterial enteric infections give promise that these vaccines should be useful both in control programs in developing countries and for immunoprophylaxis against travellers' diarrhea.