We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
A live vaccine rapidly protects against cholera in an infant rabbit model.
- Authors
Hubbard, Troy P.; Billings, Gabriel; Dörr, Tobias; Sit, Brandon; Warr, Alyson R.; Kuehl, Carole J.; Kim, Minsik; Delgado, Fernanda; Mekalanos, John J.; Lewnard, Joseph A.; Waldor, Matthew K.
- Abstract
An engineered cholera vaccine candidate mediates colonization resistance and disease protection within 1 day in an infant rabbit model. Designer bugs as drugs: The endemic persistence and outbreaks of Vibrio cholerae indicate a need for new methods of control; in this issue, two groups investigated the potential of engineered bacteria to mediate cholera resistance in animal models. Mao et al. discovered that lactic acid production by the probiotic Lactococcus lactis rendered the infant mouse gut hostile to V. cholerae and engineered L. lactis to detect breakthrough infection. Hubbard et al. extensively modified a contemporary V. cholerae strain for a live oral vaccine, which resulted in an attenuated strain that could protect infant rabbits from V. cholerae challenge within 24 hours of vaccine administration, indicating that the protective effects were not dependent on adaptive immunity. These papers showcase innovative approaches to tackling cholera. 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.
- Subjects
CHOLERA vaccines; VACCINE effectiveness; VIBRIO cholerae; DISEASE progression; ANIMAL models in research
- Publication
Science Translational Medicine, 2018, Vol 10, Issue 445, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.aap8423