A live vaccine rapidly protects against cholera in an infant rabbit model

Troy P. Hubbard, Gabriel Billings, Tobias Dörr, Brandon Sit, Alyson R. Warr, Carole J. Kuehl, Minsik Kim, Fernanda Delgado, John J. Mekalanos, Joseph A. Lewnard, Matthew K. Waldor

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16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbereaap8423
JournalScience Translational Medicine
Volume10
Issue number445
DOIs
Publication statusPublished - 2018 Jun 13

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Hubbard, T. P., Billings, G., Dörr, T., Sit, B., Warr, A. R., Kuehl, C. J., Kim, M., Delgado, F., Mekalanos, J. J., Lewnard, J. A., & Waldor, M. K. (2018). A live vaccine rapidly protects against cholera in an infant rabbit model. Science Translational Medicine, 10(445), [eaap8423]. https://doi.org/10.1126/scitranslmed.aap8423