title: Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis.
abstract: The TB Vaccine Cluster project funded by the EU Fifth Framework programme aims to provide novel vaccines against tuberculosis that are suitable for evaluation in humans. This paper describes the studies of the protective efficacy of vaccines in a guinea pig aerosol-infection model of primary tuberculosis. The objective was to conduct comparative evaluations of vaccines that had previously demonstrated efficacy in other animal models. Groups of 6 guinea pigs were immunized with vaccines provided by the relevant EU Vaccine Cluster partners. Survival over 17 or 26 weeks was used as the principal measure of vaccine efficacy following aerosol challenge with H37Rv. Counts of mycobacteria in lungs and spleens, and histopathological changes in the lungs, were also used to provide evidence of protection. A total of 24 vaccines were evaluated in 4 experiments each of a different design. A heterologous prime-boost strategy of DNA and MVA, each expressing Ag85A and a fusion protein of ESAT-6 and Ag85B in adjuvant, protected the guinea pigs to the same extent as BCG. Genetically modified BCG vaccines and boosted BCG strategies also protected guinea pigs to the same extent as BCG but not statistically significantly better. A relatively high aerosol-challenge dose and evaluation over a protracted time post-challenge allowed superior protection over BCG to be demonstrated by BCG boosted with MVA and fowl pox vectors expressing Ag85A.
authors.affiliation: Health Protection Agency, Porton Down, Salisbury SP4 OJG, UK. ann.williams@camr.org.uk
authors.forename: Ann
authors.initials: A
authors.lastname: Williams
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Hatch
authors.forename: Simon O
authors.initials: SO
authors.lastname: Clark
authors.forename: Karen E
authors.initials: KE
authors.lastname: Gooch
authors.forename: Kim A
authors.initials: KA
authors.lastname: Hatch
authors.forename: Graham A
authors.initials: GA
authors.lastname: Hall
authors.forename: Kris
authors.initials: K
authors.lastname: Huygen
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Leander
authors.initials: L
authors.lastname: Grode
authors.forename: Peter
authors.initials: P
authors.lastname: Seiler
authors.forename: Carlos
authors.initials: C
authors.lastname: Martin
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
authors.forename: Priscille
authors.initials: P
authors.lastname: Brodin
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Pym
authors.forename: Wilfried
authors.initials: W
authors.lastname: Dalemans
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Yves
authors.initials: Y
authors.lastname: Lobet
authors.forename: Nilu
authors.initials: N
authors.lastname: Goonetilleke
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.forename: Adrian
authors.initials: A
authors.lastname: Hill
authors.forename: Tanya
authors.initials: T
authors.lastname: Parish
authors.forename: Debbie
authors.initials: D
authors.lastname: Smith
authors.forename: Neil G
authors.initials: NG
authors.lastname: Stoker
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Lowrie
authors.forename: Gunilla
authors.initials: G
authors.lastname: Källenius
authors.forename: Stefan
authors.initials: S
authors.lastname: Svenson
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pawlowski
authors.forename: Karen
authors.initials: K
authors.lastname: Blake
authors.forename: Philip D
authors.initials: PD
authors.lastname: Marsh
mesh_terms: D000336:Aerosols; D000818:Animals; D001500:BCG Vaccine / Q000627:therapeutic use; D015169:Colony Count, Microbial / Q000379:methods; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005062:European Union; D006168:Guinea Pigs; D006801:Humans; D008168:Lung / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000302:isolation & purification; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control; D014611:Vaccination / Q000379:methods
chemical_list: D000336:Aerosols; D001500:BCG Vaccine; D032581:Tuberculosis Vaccines