Route of delivery to the airway influences the distribution of pulmonary disease but not the outcome of Mycobacterium tuberculosis infection in rhesus macaques

Laura Sibley, Michael Dennis, Charlotte Sarfas, Andrew White, Simon Clark, Fergus Gleeson, Anthony McIntyre, Emma Rayner, Geoffrey Pearson, Ann Williams, Philip Marsh, Sally Sharpe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)141-149
Number of pages9
JournalTuberculosis
Volume96
DOIs
Publication statusPublished - 1 Jan 2016

Bibliographical note

Funding Information:
This work was supported by The Gates Foundation and the Department of Health, UK . The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. We thank the staff of the Biological Investigations Group at PHE Porton and the PHE macaque colonies for assistance in conducting studies; Tracy Benford and Faye Lanni for bacteriology and aerobiology support, and Donna Smyth for assistance with imaging.

Funding Information:
This work was supported by The Gates Foundation and the Department of Health, UK .

Keywords

  • Challenge route
  • Immune response
  • Non-human primate
  • Tuberculosis

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