| Literature DB >> 29899024 |
Troy P Hubbard1,2, Gabriel Billings1,2, Tobias Dörr1,2, Brandon Sit1,2, Alyson R Warr1,2, Carole J Kuehl1,2, Minsik Kim1,2, Fernanda Delgado2,3, John J Mekalanos1, Joseph A Lewnard4, Matthew K Waldor5,2,3,6.
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.Entities:
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Year: 2018 PMID： 29899024 PMCID： PMC6500431 DOI： 10.1126/scitranslmed.aap8423
Source DB: PubMed Journal: Sci Transl Med ISSN： 1946-6234 Impact factor: 17.956