Surveillance of Daughter Micronodule Formation Is a Key Factor for Vaccine Evaluation Using Experimental Infection Models of Tuberculosis in Macaques

Isabel Nogueira, Martí Català, Andrew D. White, Sally A. Sharpe, Jordi Bechini, Clara Prats, Cristina Vilaplana, Pere Joan Cardona*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Tuberculosis (TB) is still a major worldwide health problem and models using non-human primates (NHP) provide the most relevant approach for vaccine testing. In this study, we analysed CT images collected from cynomolgus and rhesus macaques following exposure to ultra-low dose Mycobacterium tuberculosis (Mtb) aerosols, and monitored them for 16 weeks to evaluate the impact of prior intradermal or inhaled BCG vaccination on the progression of lung disease. All lesions found (2553) were classified according to their size and we subclassified small micronodules (<4.4 mm) as ‘isolated’, or as ‘daughter’, when they were in contact with consolidation (described as lesions ≥ 4.5 mm). Our data link the higher capacity to contain Mtb infection in cynomolgus with the reduced incidence of daughter micronodules, thus avoiding the development of consolidated lesions and their consequent enlargement and evolution to cavitation. In the case of rhesus, intradermal vaccination has a higher capacity to reduce the formation of daughter micronodules. This study supports the ‘Bubble Model’ defined with the C3HBe/FeJ mice and proposes a new method to evaluate outcomes in experimental models of TB in NHP based on CT images, which would fit a future machine learning approach to evaluate new vaccines.

Original languageEnglish
Article number236
JournalPathogens
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2023

Bibliographical note

Funding Information:
This research was funded by ‘La Caixa’ Foundation (ID 100010434), under agreement LCF/PR/GN16/10290002 and AGAUR 2017 SGR 00500, 2021 SGR 00920 and 2021 SGR 00934.

Publisher Copyright:
© 2023 by the authors.

Keywords

  • BCG vaccine
  • aerosol vaccination
  • bubble model
  • computed tomography scanner
  • macaque
  • non-human primate
  • tuberculosis

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