Antigen-specific memory B-cell responses in Bangladeshi adults after one- or two-dose oral killed cholera vaccination and comparison with responses in patients with naturally acquired cholera

Abstract

The mediators of protective immunity against cholera are currently unknown, but memory B-cell responses may play a central role in facilitating long-term and anamnestic responses against Vibrio cholerae, the cause of cholera. We compared memory B-cell responses in adults with natural cholera in Bangladesh (n = 70) to responses in Bangladeshi adults after one-dose (n = 30) or two-dose (n = 30) administration of an oral killed cholera vaccine, WC-rBS (Dukoral; Crucell), assessing the responses at the acute stage of disease or prevaccination and then on days 3, 30, 90, 180, 270, and 360. Individuals with natural cholera developed prominent vibriocidal and plasma anti-cholera toxin B subunit (CtxB) and lipopolysaccharide (LPS) IgG and IgA responses, but these responses returned to baseline by 1 year of follow-up. Vaccinees developed plasma anti-CtxB and anti-LPS IgG and IgA responses that were generally comparable to those in individuals recovering from natural disease, but vibriocidal responses were lower in vaccinees than in infected patients. Individuals recovering from natural disease developed memory B-cell IgG and IgA anti-CtxB and anti-LPS responses by day 30, and these responses were detectable through at least days 180 to 360. In contrast, we detected no IgA or IgG memory B-cell responses to LPS in vaccinees; anti-CtxB IgA responses were only detectable on day 30, and anti-CtxB IgG responses were detectable until days 90 to 180, compared to days 270 to 360 in patients. These findings may explain in part the relatively short-term protection afforded by oral cholera vaccination compared to natural disease.

Figures

Fig. 1.

Vibriocidal responses in vaccinees and cholera patients. The vibriocidal antibody responses in plasma in Bangladeshi adults who received one or two doses of WC-rBS cholera vaccine separated by 2 weeks (days 0 and 14) and in adult cholera patients were graphed. The columns indicate mean reciprocal end titers, and error bars represent the standard errors of the mean. The Wilcoxon signed-rank test was used for analyses of the data. An asterisk denotes a statistically significant difference (P < 0.05) from the baseline (day 0 or 2) titer. Mean fold changes and responder frequencies are also listed. #, Statistically significant difference among the study groups (P < 0.05).

Fig. 2.

Plasma anti-CtxB and LPS responses in adult vaccinees and cholera patients. The CtxB and LPS antibody responses in plasma in Bangladeshi adults who received one or two doses of WC-rBS cholera vaccine separated by 2 weeks (days 0 and 14) and in adult cholera patients were assessed. The columns indicate mean responses, and the error bars represent standard errors of the mean. The Wilcoxon signed-rank test was used for analyses of the data. An asterisk denotes a statistically significant difference (P < 0.05) from the baseline (day 0 or 2) titer. Mean fold changes and responder frequencies are also listed. #, statistically significant difference between the two vaccine cohorts (P < 0.05).

Fig. 3.

Anti-CtxB and LPS memory B-cell responses in adult vaccinees and cholera patients. The CtxB and LPS-specific memory B-cell responses in Bangladeshi adults who received one or two doses of WC-rBS cholera vaccine separated by 2 weeks (days 0 and 14) and in adult cholera patients, expressed as the percent antigen-specific responses of total isotype-specific memory B cells, were assessed. Bars represent mean responses and standard errors of the mean. The Wilcoxon signed-rank test was used for analyses of the data. An asterisk denotes a statistically significant difference (P < 0.05) from the baseline (day 0 or 2) titer. #, statistically significant difference between vaccinees and cholera patients (P < 0.05).