Plasma and memory B cell responses targeting O-specific polysaccharide (OSP) are associated with protection against Vibrio cholerae O1 infection among household contacts of cholera patients in Bangladesh

Abstract

Background: The mediators of protection against cholera, a severe dehydrating illness of humans caused by Vibrio cholerae, are unknown. We have previously shown that plasma IgA as well as memory B IgG cells targeting lipopolysaccharide (LPS) of Vibrio cholerae O1 correlate with protection against V. cholerae O1 infection among household contacts of cholera patients. Protection against cholera is serogroup specific, and serogroup specificity is defined by the O-specific polysaccharide (OSP) component of LPS. Therefore, we prospectively followed household contacts of cholera patients to determine whether OSP-specific immune responses present at the time of enrollment are associated with protection against V. cholerae infection.

Methodology: In this study, we enrolled two hundred forty two household contacts of one hundred fifty index patients who were infected with Vibrio cholerae. We determined OSP-specific memory B cells and plasma IgA, IgG and IgM antibody responses on study entry (day 2).

Principle findings: The presence of OSP-specific plasma IgA, IgM, and IgG antibody responses on study entry were associated with a decrease in the risk of infection in household contacts (IgA, p = 0.015; IgM, p = 0.01, and IgG, p = 0.024). In addition, the presence of OSP-specific IgG memory B cell responses in peripheral blood on study entry was also associated with a decreased risk of infection (44% reduction; 95% CI: 31.1 to 99.8) in contacts. No protection was associated with cholera toxin B subunit (CtxB)-specific memory B cell responses.

Conclusion: These results suggest that immune responses that target OSP, both in plasma and memory responses, may be important in mediating protection against infection with V. cholerae O1.

Fig 1. Enrollment and classification of study participants (A-cholera index patients, and B-household contacts of index patients).

Infected and un-infected contacts who had no diarrhea in the week before presentation were included in the immunologic analysis. Index patients, who had symptoms of diarrhea equal or less than 24 hours before enrollment, were also included in the analysis.

Fig 2. Plasma vibriocidal antibody titers upon enrollment.

Bars represent geometric mean responses. P values for statistical significant differences between groups determined by Mann-Whitney U test.

Fig 3

Plasma OSP-specific IgA, IgG and IgM antibody values (A, B and C, respectively) upon enrollment (day 2). Bars represent median responses. P values for statistical significant differences between groups determined by Mann-Whitney U test.

Fig 4

OSP-specific IgA (A), IgG (B) and IgM (C) memory B cell responses upon enrollment (day 2). P values for statistical significant differences between groups determined by Mann-Whitney U test.

Fig 5

CTB-specific IgA, IgG and IgM memory B cell responses upon enrollment (day 2) (A, B and C, respectively).