title: 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.
authors.affiliation: Jenner Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Griffiths
authors.forename: Elena
authors.initials: E
authors.lastname: Stylianou
authors.forename: Hazel C
authors.initials: HC
authors.lastname: Poyntz
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Betts
authors.forename: Helen A
authors.initials: HA
authors.lastname: Fletcher
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology / Q000494:pharmacology*; D002772:Cholera Toxin / Q000494:pharmacology*; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018709:Statistics, Nonparametric; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*
chemical_list: D001500:BCG Vaccine; D020381:Interleukin-17; D002772:Cholera Toxin