title: Route of delivery to the airway influences the distribution of pulmonary disease but not the outcome of Mycobacterium tuberculosis infection in rhesus macaques.
abstract: Non-human primates (NHP) provide a key component in the preclinical assessment pathway for new TB vaccines. In the established models, Mycobacterium tuberculosis challenge is typically delivered to airways of macaques either by aerosol or bronchoscopic instillation and therefore, an understanding of these delivery routes would facilitate the comparison of data generated from models using different challenge methods. This study compared the clinical effects, antigen-specific IFNγ response profiles and disease burden following delivery of comparable doses of M. tuberculosis to the lungs of rhesus macaques by either aerosol or bronchoscopic instillation. The outcome of infection in terms of clinical effects and overall disease burden was comparable between both routes of challenge. However, the pathology in the lungs differed as disease was localised to the site of inoculation following bronchoscopic instillation while aerosol exposure resulted in lesions being evenly distributed through the lung. Whilst the IFNγ response to PPD was similar, responses to CFP10 and ESAT6 peptide pools measured with an ex vivo ELISPOT differed with regards to responses to the N-terminal regions depending on the route of infection. Both challenge routes therefore provide valid and comparable models for evaluation of new TB vaccines, although subtle differences in host responses may occur.
authors.affiliation: National Infection Service, Public Health England, Porton Down, Wiltshire, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Sibley
authors.affiliation: National Infection Service, Public Health England, Porton Down, Wiltshire, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Dennis
authors.affiliation: National Infection Service, Public Health England, Porton Down, Wiltshire, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Sarfas
authors.affiliation: National Infection Service, Public Health England, Porton Down, Wiltshire, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: White
authors.affiliation: National Infection Service, Public Health England, Porton Down, Wiltshire, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Clark
authors.affiliation: The Churchill Hospital, Headington, Oxford, UK.
authors.forename: Fergus
authors.initials: F
authors.lastname: Gleeson
authors.affiliation: The Churchill Hospital, Headington, Oxford, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: McIntyre
authors.affiliation: National Infection Service, Public Health England, Porton Down, Wiltshire, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Rayner
authors.affiliation: National Infection Service, Public Health England, Porton Down, Wiltshire, UK.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Pearson
authors.affiliation: National Infection Service, Public Health England, Porton Down, Wiltshire, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Williams
authors.affiliation: National Infection Service, Public Health England, Porton Down, Wiltshire, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Marsh
authors.affiliation: National Infection Service, Public Health England, Porton Down, Wiltshire, UK. Electronic address: Sally.Sharpe@phe.gov.uk.
authors.forename: Sally
authors.initials: S
authors.lastname: Sharpe
mesh_terms: D000336:Aerosols; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001999:Bronchoscopy; D004195:Disease Models, Animal; D058501:Enzyme-Linked Immunospot Assay; D054884:Host-Pathogen Interactions; D019570:Inhalation Exposure; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D059425:Interferon-gamma Release Tests; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology
chemical_list: D000336:Aerosols; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma
keywords: Challenge route; Immune response; Non-human primate; Tuberculosis