Cholera caused by Vibrio cholerae O139 could reemerge, and proactive development of an effective O139
vaccine would be prudent. To define immunoreactive and potentially immunogenic
carbohydrate targets of Vibrio cholerae O139, we assessed immunoreactivities of various
O-specific polysaccharide (OSP)-related saccharides with plasma from humans hospitalized with
cholera caused by O139, comparing responses to those induced in recipients of a commercial oral whole-cell killed bivalent (O1 and O139)
cholera vaccine (WC-O1/O139). We also assessed
conjugate vaccines containing selected subsets of these saccharides for their ability to induce protective immunity using a mouse model of
cholera. We found that patients with wild-type O139
cholera develop
IgM,
IgA, and
IgG immune responses against O139 OSP and many of its fragments, but we were able to detect only a moderate
IgM response to purified O139 OSP-core, and none to its fragments, in immunologically naive recipients of WC-O1/O139. We found that immunoreactivity of O139-specific
polysaccharides with
antibodies elicited by wild-type
infection markedly increase when saccharides contain
colitose and
phosphate residues, that a synthetic terminal tetrasaccharide fragment of OSP is more immunoreactive and protectively immunogenic than complete OSP, that native OSP-core is a better protective immunogen than the synthetic OSP lacking core, and that functional vibriocidal activity of
antibodies predicts in vivo protection in our model but depends on
capsule thickness. Our results suggest that O139 OSP-specific responses are not prominent following vaccination with a currently available oral
cholera vaccine in immunologically naive humans and that
vaccines targeting V. cholerae O139 should be based on native OSP-core or terminal tetrasaccharide. IMPORTANCE
Cholera is a severe dehydrating illness of humans caused by Vibrio cholerae serogroup O1 or O139. Protection against
cholera is serogroup specific, and serogroup specificity is defined by
O-specific polysaccharide (OSP). Little is known about immunity to O139 OSP. In this study, we used synthetic fragments of the O139 OSP to define immune responses to OSP in humans recovering from
cholera caused by V. cholerae O139, compared these responses to those induced by the available O139
vaccine, and evaluated O139 fragments in next-generation
conjugate vaccines. We found that the terminal tetrasaccharide of O139 is a primary immune target but that the currently available bivalent
cholera vaccine poorly induces an anti-O139 OSP response in immunologically naive individuals.