Intestinal immunization with soluble bacterial antigens: the example of cholera toxoid

The studies described are aimed at a better understanding of the intestinal immunological system and its role in protection against enteric infection. The cellular kinetics of the intestinal immune response to cholera toxoid were studied in rats and the protection afforded by toxoid immunization was studied in dogs. Memory was demonstrated in the gut immune system. Plasma cells containing IgA antitoxin appeared in large numbers in gut lamina propria when intraduodenal boosting followed either intraperitoneal priming or prolonged oral priming, intraperitoneal priming being the most efficient. Immunization by the intraperitoneal route alone produced no response in small bowel lamina propria. Lamina propria plasma cells were derived from precursors in Peyer's patches or mesenteric lymph nodes which migrated through the thoracic duct and systemic circulation before homing to the gut. Dogs were immunized parenterally with cholera toxin or toxoid and challenged orally with Vibrio cholerae. Protection correlated closely with serum antitoxin titres and was usually brief. Passive intravenous immunization with IgG antitoxin was also protective. In contrast, subcutaneous priming followed by oral boosting yielded longer protection without elevated serum antitoxin titres. Antitoxin was detected in jejunal washings only briefly after local boosting. The mechanism by which protection is prolonged is unclear but its greater duration after parenteral priming and oral boosting emphasizes the importance of stimulating the gut immune mechanism in attempts to immunize against enteric bacterial infections. The parenteral-oral squence may be an effective means of immunizing the intestine with non-replicating protein antigens.