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Journal article

Cholera toxin enhances vaccine-induced protection against Mycobacterium tuberculosis challenge in mice

Abstract:
Interleukin (IL)-17 is emerging as an important cytokine in vaccine-induced protection against tuberculosis disease in animal models. Here we show that compared to parenteral delivery, BCG delivered mucosally enhances cytokine production, including interferon gamma and IL-17, in the lungs. Furthermore, we find that cholera toxin, delivered mucosally along with BCG, further enhances IL-17 production by CD4+ T cells over mucosal BCG alone both in the lungs and systemically. This boosting effect of CT is also observed using a vaccine regimen of BCG followed by the candidate vaccine MVA85A. Using a murine Mycobacterium tuberculosis (M.tb) aerosol challenge model, we demonstrate the ability of cholera toxin delivered at the time of a priming BCG vaccination to improve protection against tuberculosis disease in a manner at least partially dependent on the observed increase in IL-17. This observed increase in IL-17 in the lungs has no adverse effect on lung pathology following M.tb challenge, indicating that IL-17 can safely be boosted in murine lungs in a vaccine/M.tb challenge setting.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1371/journal.pone.0078312

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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Jenner Institute
Role:
Author


Publisher:
Public Library of Science
Journal:
PLoS ONE More from this journal
Volume:
8
Issue:
10
Pages:
ARTN e78312
Publication date:
2013-10-23
Acceptance date:
2013-09-13
DOI:
EISSN:
1932-6203
ISSN:
1932-6203


Language:
English
Keywords:
UUID:
uuid:242c46b2-a08d-4e76-95d6-aae8377e2d76
Local pid:
pubs:436416
Source identifiers:
436416
Deposit date:
2013-12-12

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