PROTECTIVE ANTITOXIC CHOLERA IMMUNITY IN MICE: INFLUENCE OF ROUTE AND NUMBER OF IMMUNIZATIONS AND MODE OF ACTION OF PROTECTIVE ANTIBODIES

Abstract

An adult mouse model was elaborated for studies of experimental cholera (Vibrio cholerae enterotoxin-induced intestinal secretion) and protective antitoxic immunity in ligated small bowel loops or intact small intestine. Mice of different inbred strains varied markedly in intestinal susceptibility to toxin, C57Bl being the most sensitive strain tested. Fluid accumulation started within 1 h after the inoculation of toxin and was maximal after 5 h, whereafter recovery gradually ensued. The dose-response curve was sigmoid, the ED50 of crude toxin being equivalent to about 0.1 .mu.g purified toxin/cm in the loops and 0.3 .mu.g/cm in the nonligated intestine. Two peroral (p.o.) immunizations induced significant protective immunity which increased markedly after 2 further immunizations by the same route. Additional p.o. immunizations did not appreciably enhance the protective immunity any further. I.v. vaccination had to be repeated more than 5 times before intestinal immunity could be observed. No correlation between serum antitoxin titers and protective immunity was found. EM examination revealed that whereas peroxidase-coupled cholera toxin bound tightly to intestinal microvilli from unimmunized or 5-times i.v. immunized mice it did not bind to the microvilli of p.o. immunized animals. Apparently the protective immunity is mediated exclusively by locally produced antibodies which prevent the binding of toxin to the gut epithelium.