Immune responses to O-specific polysaccharide

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 [greater than or equal to] 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.