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Infect Immun. 1979 March; 23(3): 729-736

Immunity to Enterotoxigenic Escherichia coli

Myron M. Levine, David R. Nalin, David L. Hoover, Erick J. Bergquist, Richard B. Hornick and Charles R. Young

1 Center for Vaccine Development, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, Maryland 21201

ABSTRACT

Enterotoxigenic Escherichia coli strains represent the most frequent etiological agent of travelers diarrhea. Challenge studies with several of these strains were undertaken in volunteers to evaluate the mechanisms of disease-induced immunity. Seventeen students and other community volunteers were given 106 or 108 organisms of E. coli B7A (O148:H28), which produces heat-labile and heat-stable enterotoxins. Ten individuals developed diarrheal illness closely resembling natural travelers diarrhea; of these ten, rises in titer of serum antitoxin and anti-O antibody occurred in eight (80%). Eight of the volunteers who developed diarrhea in the first test agreed to undergo rechallenge 9 weeks later with 108 B7A organisms. Only one of these eight "veterans" developed diarrhea versus seven of twelve controls given the same challenge (P = 0.05). Despite clinical protection, all "veterans" excreted B7A after rechallenge. Four controls who developed diarrhea during the homologous B7A rechallenge test were rechallenged 9 weeks later with 109 organisms of E. coli strain E2528-C1 (O25:H-), which produces only heat-labile enterotoxin and possesses a different O, H, and pili antigen composition than B7A. Three of four "veterans" and two of six controls developed comparable diarrhea. These studies demonstrate that prior disease due to enterotoxigenic E. coli confers homologous immunity against subsequent challenge, and the operative mechanism apparently is not bactericidal and is not mediated by serum anti-O antibodies. Heterologous protection was not conferred where the only common antigen was heat-labile enterotoxin, indicating that serum infection-derived antitoxin to heat-labile enterotoxin also is not protective.

Infect Immun. 1979 March; 23(3): 729-736




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