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 language | English |
|---|---|
| Article number | eaap8423 |
| Journal | Science Translational Medicine |
| Volume | 10 |
| Issue number | 445 |
| DOIs | |
| Publication status | Published - 2018 Jun 13 |
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All Science Journal Classification (ASJC) codes
- Medicine(all)
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A live vaccine rapidly protects against cholera in an infant rabbit model. / 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.
In: Science Translational Medicine, Vol. 10, No. 445, eaap8423, 13.06.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - A live vaccine rapidly protects against cholera in an infant rabbit model
AU - Hubbard, Troy P.
AU - Billings, Gabriel
AU - Dörr, Tobias
AU - Sit, Brandon
AU - Warr, Alyson R.
AU - Kuehl, Carole J.
AU - Kim, Minsik
AU - Delgado, Fernanda
AU - Mekalanos, John J.
AU - Lewnard, Joseph A.
AU - Waldor, Matthew K.
PY - 2018/6/13
Y1 - 2018/6/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85048400390&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048400390&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.aap8423
DO - 10.1126/scitranslmed.aap8423
M3 - Article
C2 - 29899024
AN - SCOPUS:85048400390
VL - 10
JO - Science Translational Medicine
JF - Science Translational Medicine
SN - 1946-6234
IS - 445
M1 - eaap8423
ER -