Intestinal immune responses in patients infected with enterotoxigenic Escherichia coli and in vaccinees

Abstract

Immune responses against enterotoxigenic Escherichia coli (ETEC) were examined in Bangladeshi adults with naturally acquired disease and compared to responses in age-matched Bangladeshi volunteers who had been orally immunized with a vaccine consisting of inactivated ETEC bacteria expressing different colonization factor antigens (CFs) and the B subunit of cholera toxin. B-cell responses in duodenal biopsy samples, feces, intestinal washings, and blood were determined. Because most of the patients included in the study were infected with ETEC expressing CS5, immune responses to this CF were studied most extensively. Vaccinees and patients had comparable B-cell responses against this antigen in the duodenum: the median numbers of antibody-secreting cells (ASC) were 3,300 immunoglobulin A (IgA) ASC/10(7) mononuclear cells (MNC) in the patient group (n = 8) and 1,200 IgA ASC/10(7) MNC in the vaccinees (n = 13) (not a significant difference). Similarly, no statistically significant differences were seen in the levels of duodenal B cells directed against enterotoxin among vaccinees and patients. A comparison of the capacities of the various methods used to assess mucosal immune responses revealed a correlation between numbers of circulating B cells and antibody levels in saponin extracts of duodenal biopsy samples (r = 0.58; n = 13; P = 0.04) after vaccination. However, no correlation was seen between blood IgA ASC and duodenal IgA ASC after two doses of vaccine. Still, a correlation between numbers of CF-specific B cells in blood sampled from patients early during infection and numbers of duodenal B cells collected 1 week later was apparent (r = 0.70; n = 10; P = 0.03).

FIG. 1

Duodenal IgA ASC responses against CFAs and CTB in adult Bangladeshi vaccinees and patients. Open circles, individual preimmune values for volunteers; solid circles, individual values seen 7 days after two oral doses of the ETEC vaccine, i.e., on day 21; triangles, individual values for patients on day 3 after hospitalization; inverted triangles, individual values for patients on day 9; horizontal bars, median ASC values. No statistically significant differences (NS, P ≥ 0.05) were seen between vaccinees and patients monitored either on day 3 or on day 9.

FIG. 2

CS5-specific duodenal ASC responses of the IgA, IgM, and IgG isotypes monitored in vaccinees and patients. Bars, geometric mean values; error bars, 1 SEM.

FIG. 3

Blood IgA ASC responses against CFAs and CTB in adult Bangladeshi vaccinees and patients. Open circles, individual preimmune values for volunteers; solid circles, individual postimmunization values seen after two oral doses of the ETEC vaccine; triangles, individual values for patients on day 3 after hospitalization; inverted triangles, individual values for patients on day 9; horizontal bars, median ASC values. NS, P ≥ 0.05; ∗, P < 0.05 to 0.01; ∗∗, P < 0.01 to 0.001.