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Sci Transl Med. 2018 Jun 13;10(445). pii: eaap8423. doi: 10.1126/scitranslmed.aap8423.

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

Author information

1
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
2
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
3
Howard Hughes Medical Institute, Boston, MA 02115, USA.
4
Center for Communicable Disease Dynamics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
5
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. mwaldor@research.bwh.harvard.edu.
6
Department of Immunology and Infectious Disease, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.

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 probiotic-like 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.

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