Arousal of mucosal secretory immunoglobulin A antitoxin in rats immunized with Escherichia coli heat-labile enterotoxin

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Abstract
Specific serum and mucosal antitoxin levels were determined by enzyme-linked immunosorbent assays in rats immunized with E. coli heat-labile enterotoxin (LT). Immunization by means of a parenteral prime followed by peroral boosts was the only approach that aroused titers of both serum IgG antitoxin and mucosal secretory IgA antitoxin that were increased .gtoreq. 4-fold over control values. Primary parenteral immunization was effective when given either i.p. or s.c. with either Freund complete adjuvant or alum as the adjuvant. The magnitude of the mucosal secretory IgA antitoxin response and the degree of protection against challenge with either LT or viable LT-producing organisms were related to the number and dosage of peroral boosts. LT antigenicity, as determined by enzyme-linked immunosorbent assay, was progressively reduced by toxoiding it with increasing amounts of glutaraldehyde or a carbodiimide; when LT antigenicity was reduced by > 50%, the effectiveness of the toxoid in stimulating mucosal antitoxin and providing protection was compromised. Strong protection extended for > 6 wk only in rats immunized with a sufficient peroral dosage of LT to arouse mucosal secretory IgA antitoxin titers at least 4-fold greater than those of controls. Thus, the ability of LT to stimulate a mucosal secretory IgA antitoxin response appears to be dependent on the antigenicity, route and dosage of this immunogen; they suggest that the duration of protection in animals immunized by the peroral route is related to the extent of arousal of mucosal secretory IgA antitoxin.