Immune responses to O-specific polysaccharide (OSP) in North American adults infected with Vibrio cholerae O1 Inaba

Background Antibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae may protect against cholera; however, little is known about this immune response in infected immunologically naïve humans. Methodology We measured serum anti-OSP antibodies in adult North American volunteers experimentally infected with V. cholerae O1 Inaba El Tor N16961. We also measured vibriocidal and anti-cholera toxin B subunit (CtxB) antibodies and compared responses to those in matched cholera patients in Dhaka, Bangladesh, an area endemic for cholera. Principal findings We found prominent anti-OSP antibody responses following initial cholera infection: these responses were largely IgM and IgA, and highest to infecting serotype with significant cross-serotype reactivity. The anti-OSP responses peaked 10 days after infection and remained elevated over baseline for ≥ 6 months, correlated with vibriocidal responses, and may have been blunted in blood group O individuals (IgA anti-OSP). We found significant differences in immune responses between naïve and endemic zone cohorts, presumably reflecting previous exposure in the latter. Conclusions Our results define immune responses to O-specific polysaccharide in immunologically naive humans with cholera, find that they are largely IgM and IgA, may be blunted in blood group O individuals, and differ in a number of significant ways from responses in previously humans. These differences may explain in part varying degrees of protective efficacy afforded by cholera vaccination between these two populations. Trial registration number ClinicalTrials.gov NCT01895855.
Author summary Cholera is an acute, secretory diarrheal disease caused by Vibrio cholerae O1. There is a growing body of evidence that immune responses targetting the O-specific polysaccharide (OSP) of V. cholerae are associated with protecton against cholera. Despite this, little is known about immune responses targeting OSP in immunologically naive individals. Cholera affects populations in severely resource-limited areas. To address this, we assessed anti-OSP immune responses in North American volunteers experimentally infected with wild type V. cholerae O1 El Tor Inaba strain N16961. We found that antibody responses were largely IgM and IgA, cross-reacted to both Inaba and Ogawa serotypes, and correlated with vibriocidal responses. We found no association of responses to severity of disease, but did find that blood group O individuals mounted lower IgA fold-changes to OSP than did non-blood group O individuals. Individuals with blood group O are at particular risk for severe cholera, and are less well protected against cholera following oral vaccination. We also compared anti-OSP responses in previously unexposed individuals to responses in matched endemic zone patients, and found a number of significant differences. Such differences may explain in part the varying degrees of protective efficacy afforded by cholera vaccination between these two populations.