Immune response, ciprofloxacin activity, and gender differences after human experimental challenge by two strains of enterotoxigenic Escherichia coli

Abstract

In order to test vaccines against enterotoxigenic Escherichia coli (ETEC)-induced diarrhea, challenge models are needed. In this study we compared clinical and immunological responses after North American volunteers were orally challenged by two ETEC strains. Groups of approximately eight volunteers received 10(9) or 10(10) CFU of E. coli B7A (LT+ ST+ CS6+) or 10(8) or 10(9) CFU of E. coli H10407 (LT+ ST+ CFA/I+). About 75% of the volunteers developed diarrhea after challenge with 10(10) CFU B7A or either dose of H10407. B7A had a shorter incubation period than H10407 (P = 0.001) and caused milder illness; the mean diarrheal output after H10407 challenge was nearly twice that after B7A challenge (P = 0.01). Females had more abdominal complaints, and males had a higher incidence of fever. Ciprofloxacin generally diminished or stopped symptoms and shedding by the second day of antibiotic treatment, but four subjects shed for one to four additional days. The immune responses to colonization factors CS6 and colonization factor antigen I (CFA/I) and to heat-labile toxin (LT) were measured. The responses to CFA/I were the most robust responses; all volunteers who received H10407 had serum immunoglobulin A (IgA) and IgG responses, and all but one volunteer had antibody-secreting cell (ASC) responses. One-half the volunteers who received B7A had an ASC response to CS6, and about one-third had serum IgA or IgG responses. Despite the differences in clinical illness and immune responses to colonization factors, the immune responses to LT were similar in all groups and were intermediate between the CFA/I and CS6 responses. These results provide standards for immune responses after ETEC vaccination.

FIG. 1.

Peak number of ETEC-specific IgA ASC after challenge with E. coli B7A (top panel) or H10407 (bottom panel). Each symbol represents one volunteer. The solid lines indicate the medians, and the dotted lines indicate the threshold for a positive response.

FIG. 2.

Peak increases in serum antibody titers to CS6 and LT after challenge with ETEC strain B7A. Each symbol represents one volunteer. The solid lines indicate the medians, and the dotted lines indicate the threshold for a positive response.

FIG. 3.

Peak increases in serum antibody titers to CFA/I and LT after challenge with ETEC strain H10407. Each symbol represents one volunteer. The solid lines indicate the medians, and the dotted lines indicate the threshold for a positive response.