Respective contributions to protection of primary and booster immunization with Escherichia coli heat-labile enterotoxin in rats

Abstract

The respective contributions to protection of the route and dosage of primary and booster immunizations with Escherichia coli heat-labile enterotoxin were evaluated in rats. The degree of protection was determined by challenge with toxin and viable bacteria in ligated ileal loops, and the serum antitoxin response was assayed by enzyme-linked immunosorbent assay. Primary immunization was effective only when given by the parenteral route. The degree of protection was enhanced by a fivefold dosage increase in the primary parenteral immunization in rats given constant dosages of booster immunizations either parenterally or perorally, but not by further dosage increases. In contrast, the degree of protection rose when dosages of the booster immunizations were increased over a 25-fold range. Four weekly peroral, but only two biweekly parenteral, booster immunizations were necessary to achieve strong protection; biweekly combined parenteral and peroral booster immunizations yielded both strong, immediate and extended protection. The degree of protection against the toxin correlated with that against viable bacteria and with elevated serum antitoxin titers: all seven groups with a protection index of >5 against the toxin had strong protection against heat-labile toxin-producing strains and fourfold or greater increases in the antitoxin titers, whereas none of the nine groups with a protection index of <3 was protected against bacteria or had an equivalent antitoxin response. These observations show that once an adequate parenteral primary immunization is given, the degree of protection is influenced primarily by the dosage of the booster immunizations, the necessary number of which is dependent on their route of administration. Acute diarrheal disease caused by intestinal colonization with enterotoxigenic strains of

Effect of parenteral immunization on the local immunoglobulin A response of the intestine to Shigella flexneri antigens

“…In several studies by Klipstein et al with labile E. coli enterotoxin, it was necessary to prime the mucosal immune system with subcutaneous or intraperitoneal antigen in either complete Freund adjuvant or alum before giving oral antigen (14)(15)(16). Similarly, workers have found parenteral priming to be the key for effective stimulation of the mucosal immune response after subsequent oral antigen administration (5,18).…”

“…Indeed, one recent report demonstrates that humans who recovered from gastrointestinal infections due to Vibrio cholera are primed to achieve a memory response to a subsequent parenteral dose of V. cholera (21). Experimental animals primed parenterally with antigen in adjuvant have enhanced local IgA production to subsequent oral administration of the same antigen (5,(14)(15)(16)18).…”

Development of a vaccine of cross-linked heat-stable and heat-labile enterotoxins that protects against Escherichia coli producing either enterotoxin

“…Challenge procedures. Rats were challenged 1 week after the final boost by the instillation of test material into a single 10-cm ligated loop of distal ileum for 18 h as described previously (15,16). Previous studies have established a correlation between significant protection in this assay system and that achieved in rats challenged by intestinal contamination of the intact intestine (19).…”

“…boosts is directly related to the total p.o. dosage (15,16). Preliminary observations indicated that the amount of LT needed to achieve significant protection, using two p.o.…”

Immunoprotection against enterotoxigenic diarrhea in rabbits by peroral administration of purified colonization factor antigen I (CFA/I)

“…Development of reliable methods for producing artificially induced immunoprotection against the enterotoxigenic enteropathogens Vibrio cholerae and enterotoxigenic Escherichia coil (ETEC) has been the subject of much investigation [1][2][3][4][5][6]. Numerous experiments with cholera vibrios, cholera toxin, various cholera toxoids and ETEC heat-labile enterotoxin (LT) as immunogens in various animal species have been reported [2][3][4][5]7,8]. These studies generally lead to the conclusion that immunoprotection against V. cholerae and ETEC diarrhea is primarily dependent upon stimulation of an adequate local immune response in the intestine, the primary mechanism being secretion of specific secretory IgA antibody [2][3][4][5][6]9].…”