Immunization of Mice With Vibrio cholerae Outer-Membrane Vesicles Protects Against Hyperinfectious Challenge and Blocks Transmission

Background. Vibrio cholerae excreted by cholera patients is “hyperinfectious” (HI), which can be modeled by passage through infant mice. Immunization of adult female mice with V. cholerae outer-membrane vesicles (OMVs) passively protects suckling mice from challenge. Although V. cholerae is unable to colonize protected pups, the bacteria survive passage and have the potential to be transmitted to susceptible individuals. Here, we investigated the impact of OMV immunization and the HI state on V. cholerae transmission. Methods. Neonatal mice suckled by OMV- or sham-immunized dams were challenged with HI V. cholerae. The infectivity of spatially and temporally separate V. cholerae populations obtained from infected naive or protected pups was tested. Recombination-based in vivo expression technology was used to assess virulence gene expression within these populations. Results. OMV immunization significantly reduced colonization of neonates challenged with HI V. cholerae. Vibrio cholerae that had colonized the naive host was HI, whereas V. cholerae excreted by neonates born to OMV-immunized dams, although viable, was hypoinfectious and failed to fully induce virulence gene expression. Conclusions. OMV immunization can significantly reduce the V. cholerae burden upon challenge with HI V. cholerae and can also block transmission from immune mice by reducing the infectivity of shed bacteria.