Development of a non-human primate BCG infection model for the evaluation of candidate tuberculosis vaccines

Stephanie A. Harris, Andrew White, Lisa Stockdale, Rachel Tanner, Laura Sibley, Charlotte Sarfas, Joel Meyer, Jonathan Peter, Matthew K. O'Shea, Zita Rose Manjaly Thomas, Ali Hamidi, Iman Satti, Michael Dennis, Helen McShane*, Sally Sharpe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The lack of validated immunological correlates of protection makes tuberculosis vaccine development difficult and expensive. Using intradermal bacille Calmette-Guréin (BCG) as a surrogate for aerosol Mycobacterium tuberculosis (M.tb) in a controlled human infection model could facilitate vaccine development, but such a model requires preclinical validation. Non-human primates (NHPs) may provide the best model in which to do this. Cynomolgus and rhesus macaques were infected with BCG by intradermal injection. BCG was quantified from a skin biopsy of the infection site and from draining axillary lymph nodes, by culture on solid agar and quantitative polymerase chain reaction. BCG was detected up to 28 days post-infection, with higher amounts of BCG detected in lymph nodes after high dose compared to standard dose infection. Quantifying BCG from lymph nodes of cynomolgus macaques 14 days post-high dose infection showed a significant reduction in the amount of BCG detected in the BCG-vaccinated compared to BCG-naïve animals. Demonstrating a detectable vaccine effect in the lymph nodes of cynomolgus macaques, which is similar in magnitude to that seen in an aerosol M.tb infection model, provides support for proof-of-concept of an intradermal BCG infection model and evidence to support the further evaluation of a human BCG infection model.

Original languageEnglish
Pages (from-to)99-105
Number of pages7
JournalTuberculosis
Volume108
DOIs
Publication statusPublished - Jan 2018

Bibliographical note

Funding Information:
This work was supported by the Wellcome Trust 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. HMcS is a Wellcome Senior Clinical Research Fellow and a Jenner Institute Investigator.

Publisher Copyright:
© 2017 The Authors

Keywords

  • BCG infection
  • Non-human primate
  • Tuberculosis
  • Vaccine

Fingerprint

Dive into the research topics of 'Development of a non-human primate BCG infection model for the evaluation of candidate tuberculosis vaccines'. Together they form a unique fingerprint.

Cite this