Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility

The mechanism of protection against cholera afforded by previous illness or vaccination is currently unknown. We have recently shown that antibodies targeting O-specific polysaccharide (OSP) of correlate highly with protection against cholera. is highly motile and possesses a flagellum sheathed in OSP, and motility of correlates with virulence. Using high-speed video microscopy and building upon previous animal-related work, we demonstrate that sera, polyclonal antibody fractions, and OSP-specific monoclonal antibodies recovered from humans surviving cholera block motility at both subagglutinating and agglutinating concentrations. This antimotility effect is reversed by preadsorbing sera and polyclonal antibody fractions with purified OSP and is associated with OSP-specific but not flagellin-specific monoclonal antibodies. Fab fragments of OSP-specific polyclonal antibodies do not inhibit motility, suggesting a requirement for antibody-mediated cross-linking in motility inhibition. We show that OSP-specific antibodies do not directly affect viability, but that OSP-specific monoclonal antibody highly protects against death in the murine cholera model. We used competitive index studies to demonstrate that OSP-specific antibodies impede colonization and survival of in intestinal tissues and that this impact is motility dependent. Our findings suggest that the impedance of motility by antibodies targeting OSP contributes to protection against cholera. Cholera is a severe dehydrating illness of humans caused by is a highly motile bacterium that has a single flagellum covered in lipopolysaccharide (LPS) displaying O-specific polysaccharide (OSP), and motility correlates with its ability to cause disease. The mechanisms of protection against cholera are not well understood; however, since is a noninvasive intestinal pathogen, it is likely that antibodies that bind the pathogen or its products in the intestinal lumen contribute to protection from infection. Here, we demonstrate that OSP-specific antibodies isolated from humans surviving cholera in Bangladesh inhibit motility and are associated with protection against challenge in a motility-dependent manner.