Memory B cell and other immune responses in children receiving two doses of an oral killed cholera vaccine compared to responses following natural cholera infection in Bangladesh

Abstract

Current oral cholera vaccines induce lower protective efficacy and shorter duration of protection against cholera than wild-type infection provides, and this difference is most pronounced in young children. Despite this, there are limited data comparing immune responses in children following wild-type disease versus vaccination, especially with regard to memory responses associated with long-term immunity. Here, we report a comparison of immune responses in young children (2 to 5 years of age; n = 20) and older children (6 to 17 years of age; n = 20) given two doses of an oral killed cholera vaccine containing recombinant cholera toxin B subunit (CtxB) 14 days apart and compare these responses to those induced in similarly aged children recovering from infection with Vibrio cholerae O1 Ogawa in Bangladesh. We found that the two vaccine groups had comparable vibriocidal and lipopolysaccharide (LPS)-specific plasma antibody responses. Vaccinees developed lower levels of IgG memory B cell (MBC) responses against CtxB but no significant MBC responses against LPS. In contrast, children recovering from natural cholera infection developed prominent LPS IgG and IgA MBC responses, as well as CtxB IgG MBC responses. Plasma LPS IgG, IgA, and IgM responses, as well as vibriocidal responses, were also significantly higher in children following disease than after vaccination. Our findings suggest that acute and memory immune responses following oral cholera vaccination in children are significantly lower than those observed following wild-type disease, especially responses targeting LPS. These findings may explain, in part, the lower efficacy of oral cholera vaccination in children.

Fig 1

Vaccination and blood draw time line. Ab, plasma for vibriocidal and antigen-specific antibody assays; MBC, PBMC isolation for memory B cell assay; D, day.

Fig 2

Geometric mean reciprocal vibriocidal antibody titers by age group and vaccination status, with error bars representing 95% confidence intervals. An asterisk denotes a significant difference (P < 0.05) from the baseline (day 0 or day 2) titer.

Fig 3

Mean plasma antibody IgG (A) and IgA (B) responses to CtxB by age group as measured by ELISA, with error bars representing standard errors of the means. An asterisk denotes a significant difference (P ≤ 0.05) from the baseline (day 2).

Fig 4

Mean plasma antibody IgG (A), IgA (B), and IgM (C) responses to LPS by age group as measured by ELISA, with error bars representing standard errors of the means. An asterisk denotes a significant difference (P ≤ 0.05) from the baseline (day 2).

Fig 5

Mean antigen-specific IgG (A and C) and IgA (B and D) memory B cell responses, as percentages of total memory B cells, with error bars representing standard errors of the means, by vaccinee age group.

Fig 6

Mean antigen-specific IgG (A and C) and IgA (B and D) memory B cell responses, as percentages of total memory B cells, with error bars representing standard errors of the means. Data represent combined age group analysis.