Protective Effect of Active Immunization with Purified Escherichia coli Heat-Labile Enterotoxin in Rats

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Abstract
The protective effect of active immunization by different routes with a purified preparation of the polymyxin-release form of E. coli heat-labile toxin was evaluated in rats. Immunized animals were challenged by placing toxin into ligated ileal loops at dosages which produced either 50% or the maximum secretory response in unimmunized rats. Immunization exclusively by the parenteral route yielded significant protection. Rats were also protected when parenteral priming was followed by boosting given either directly into the duodenum or perorally 2 h after intragastric cimetidine, but not when the peroral boosts were given with bicarbonate. Immunization administered entirely by the peroral route with cimetidine yielded protection but only when the immunizing dosage was 5 .times. the effective dose in the parenteral-peroral approach. Rats immunized exclusively by the parenteral route and those boosted perorally with cimetidine were also tested, and protected, against challenge with viable organisms of strains that produce either heat-labile toxin alone or both heat-labile and heat-stable toxin, but they were not protected against a strain which produces just heat-stable toxin. Geometric mean serum antibody titers were increased by 16 .times. or more over control values in those groups of rats in which protection was achieved, with the exception of those immunized exclusively by the peroral route. Active immunization with purified E. coli heat-labile toxin results in significant protection against this toxin as well as viable organisms which produce it, but not against viable strains which produce heat-stable toxin only, and concomitant ablation of gastric secretion by the use of cimetidine renders the peroral route of immunization effective. Prophylactic immunization against diarrheal disease caused by heat-labile toxin-producing strains of E. coli may be feasible in humans.

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