Outbreaks of cholera, a rapidly fatal diarrheal disease, often spread explosively. The efficacy of reactive vaccination campaigns - deploying Vibrio cholerae vaccines during epidemics - is partially limited by the time required for vaccine recipients to develop adaptive immunity. We created HaitiV, a live attenuated cholera vaccine candidate, by deleting diarrheagenic factors from a recent clinical isolate of V. cholerae and incorporating safeguards against vaccine reversion.We demonstrate that administration of HaitiV 24 hours before lethal challenge with wild-type V. cholerae reduced intestinal colonization by the wild-type strain, slowed disease progression, and reduced mortality in an infant rabbit model of cholera. HaitiV-mediated protection required viable vaccine, and rapid protection kinetics are not consistent with development of adaptive immunity. These features suggest that HaitiV mediates probioticlike protection from cholera, a mechanism that is not known to be elicited by traditional vaccines. Mathematical modeling indicates that an intervention that works at the speed of HaitiV-mediated protection could improve the public health impact of reactive vaccination.
Bibliographical noteFunding Information:
We thank B. Davis, L. Comstock, S. Rakoff-Nahoum, A. Olive, M. Lipsitch, and members of the Waldor group for commenting on the manuscript. This work was supported by NIH AI-042347 and Howard Hughes Medical Institute (M.K.W.), F31 AI-120665 to (T.P.H.), and NSERC PGS-D 487259 to (B.S.).
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