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prophylaxis is currently recommended only for persons who cannot obtain safe food and water and who would be endangered or greatly inconvenienced if they were to get diarrhea while traveling. This particularly includes persons with serious underlying medical conditions, in whom diarrhea could present a difficult management problem.

PROSPECTS FOR VACCINE DEVELOPMENT

Current work in vaccine development against enterotoxigenic E. coli. diarrhea involves vaccines that stimulate antitoxic (antitoxin) or anti-adhesion immunity or both by means of killed antigens or attenuated strains. Recent developments have been reviewed by Levine et al. (1983). The most effective vaccines may contain antigens that stimulate both antitoxic and antibacterial immunity, producing a synergistic protective effect. It is believed that the critical site of immunity is the mucosal surface of the upper intestinal tract and that this site is protected mainly by secretory IgA antibody.

Enterotoxigenic E. coli also cause serious diarrhea and death in animals. Extensive veterinary research has focused on the development of vaccines against the organisms that produce these problems. In the veterinary studies, purified fimbrial vaccines protected newborn piglets and calves, which were suckled on immunized mothers, against death from diarrhea caused by challenge with enterotoxigenic E. coli bearing the homologous fimbriae. In addition, CFA I and CFA II fimbrial vaccines administered orally or enterally stimulated intestinal SIgA antibody to CFA and resulted in protective immunity in animal models. Studies in humans with purified CFA vaccines are beginning. If a prototype CFA vaccine is found to protect against E. coli with the homologous fimbriae, intensive research will be pursued to identify other colonization factors. Only a small number of pathogenic enterotoxigenic E. coli possess currently recognized colonization factors; other factors must be identified to ensure broad-spectrum protection by a polyvalent fimbrial vaccine.

Another approach to the development of a vaccine against enterotoxigenic E. coli involves the use of toxoids. Animal studies have shown that immunization with either B subunit or LT holotoxin elicits an immune response and a protective effect, and that holotoxin is the superior immunogen. The technology for large-scale production of B subunit has not yet been described, but the successful cloning of LT genes from a human pathogen into a high-copy plasmid vector indicates that it is possible.

Heat treatment of cholera enterotoxin results in a high molecular weight toxoid called procholeragenoid, which is comparable in immunogenicity to the parent toxin. This has been used to immunize pregnant sows. Piglets born to and suckled on the immunized sows were protected against diarrhea and death due to infection with enterotoxigenic E. coli, suggesting that procholeragenoid might serve as an oral vaccine to enhance protection against enterotoxigenic E. coli, as well as Vibrio cholerae.



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