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

BackgroundThe 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.MethodologyIn 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 findingsThe 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.ConclusionThese 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.

Immunogenicity of a bivalent killed thimerosal-free oral cholera vaccine, Euvichol, in an animal model

“…This is supported from previous studies where LPS-specific serum IgG and IgA were highly increased in cholera patients and vaccinated individuals [ 20 21 22 ]. In addition, serum IgM and secretory IgA against V. cholerae LPS generated in patients play a role in conferring protective immunity against cholera [ 23 24 ].…”

Cell mediated immune responses elicited in volunteers following immunization with candidate live oral Salmonella enterica serovar Paratyphi A attenuated vaccine strain CVD 1902

“…IgG and IgA B M responses against LPS or O-specific polysaccharides were shown to correlate with protection from natural V. cholerae clinical infection and with decreased disease severity in a human challenge model of shigellosis [38,43,46]. Data reported herein suggest that a single dose of CVD 1902 with either 10 9 or 10 10 CFU primed the hostimmune system to generate PA-specific B M that could play a role in host-immunity against PA infection.…”

“…Herein we describe in detail the induction of immune memory by evaluating PA-specific B-and T-cell-mediated effector/memory responses in PBMC from the two groups of volunteers who ingested, with buffer, a single dose of CVD 1902 containing either 10 9 or 10 10 CFU, or placebo. Previous studies reported the induction of B memory cells (B M ) against LPS, O-polysaccharides and protein antigens in humans following natural infection or after immunization with oral vaccines against S. Typhi or other enteric bacteria (e.g., Shigella, Vibrio cholerae O1, Escherichia coli) [34,[38][39][40][41][42][43][44][45]. In agreement with those earlier findings, in this study we also observed increases in the magnitudes of PA-LPS-specific IgG and IgA B M following oral immunization with S.…”

Bacteria That Cause Enteric Diseases Stimulate Distinct Humoral Immune Responses

“…This long-lasting immune response is mediated specifically by LPS and OSP-specific IgG memory B cells. Anti-toxin IgG or anti-toxin and anti-LPS IgA memory B cells do not correlate with the long-term immunity against V. cholerae ( 75 , 76 ).…”