Induction of optimal mucosal antibody responses: effects of age, immunization route(s), and dosing schedule in rats

Abstract

The antitoxin response in intestinal mucosa was studied in rats immunized either intestinally or by combined parenteral and intestinal dosing with cholera toxin or cholera toxoid. Attention was given to the duration of enteric priming and the magnitude and time course of mucosal anti-cholera toxin responses in rats of defined age. Cholera toxin given only intraduodenally was a more efficient priming immunogen in young rats than in older rats and caused priming that lasted at least 32 weeks; repeated enteric doses increased local priming and repeatedly evoked vigorous mucosal anti-cholera toxin responses which occurred rapidly and declined slowly. Results differed when a portion of the immunizing regimen was parenteral. Cholera toxoid given intraperitoneally (i.p.) caused mucosal priming that peaked promptly and then rapidly declined; parenteral boosting after enteric priming was much more effective given i.p. than subcutaneously; moreover, the booster response was brief, virtually disappearing within 11 days, and could not be reproduced by a second i.p. immunization. These results accord with evidence that parenteral immunization both stimulates and suppresses mucosal secretory immunoglobulin A responses, whereas local immunization is not known to be suppressive. Evidence for parenterally induced suppression was the rapid decline in mucosal priming after i.p. immunization, the shortened mucosal antibody response after i.p. immunization, and possibly the inability to parenterally evoke a booster response twice. In these studies, the level of priming observed at different intervals after parenteral, enteric, or combined immunization appeared to reflect the sum of priming and suppressive effects evoked by the preceding immunization(s).