title: Selection of novel TB vaccine candidates and their evaluation as DNA vaccines against aerosol challenge.
abstract: Putative TB vaccine candidates were selected from lists of genes induced in response to in vivo-like stimuli, such as low oxygen and carbon starvation or growth in macrophages, and tested as plasmid DNA vaccines for their ability to protect against Mycobacterium tuberculosis challenge in a guinea pig aerosol infection model. This vaccination method was chosen as it induces the Th1 cell-mediated immune response required against intracellular pathogens such as M. tuberculosis. Protection was assessed in the guinea pig model in terms of mycobacteria present in the lungs at 30 days post-challenge. Protection achieved by the novel candidates was compared to BCG (positive control) and saline (negative control). Four vaccines encoding for proteins such as PE and PPE proteins, a zinc metalloprotease and an acyltransferase, gave a level of protection that was statistically better than saline in the lungs. These findings have enabled us to focus on a sub-set of vaccine candidates for further evaluation using additional vaccination strategies.
authors.affiliation: Health Protection Agency, Porton Down, Salisbury SP4 0JG, UK. julia.vipond@hpa.org.uk <julia.vipond@hpa.org.uk>
authors.forename: Julia
authors.initials: J
authors.lastname: Vipond
authors.forename: Richard
authors.initials: R
authors.lastname: Vipond
authors.forename: Emma
authors.initials: E
authors.lastname: Allen-Vercoe
authors.forename: Simon O
authors.initials: SO
authors.lastname: Clark
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Hatch
authors.forename: Karen E
authors.initials: KE
authors.lastname: Gooch
authors.forename: Joanna
authors.initials: J
authors.lastname: Bacon
authors.forename: Toby
authors.initials: T
authors.lastname: Hampshire
authors.forename: Helen
authors.initials: H
authors.lastname: Shuttleworth
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Minton
authors.forename: Karen
authors.initials: K
authors.lastname: Blake
authors.forename: Ann
authors.initials: A
authors.lastname: Williams
authors.forename: Philip D
authors.initials: PD
authors.lastname: Marsh
mesh_terms: D000336:Aerosols / Q000008:administration & dosage; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D005260:Female; D006168:Guinea Pigs; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000336:Aerosols; D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA