Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 24 November 2022 / Approved: 29 November 2022 / Online: 29 November 2022 (03:29:53 CET)

A peer-reviewed article of this Preprint also exists.

Nogueira, I.; Català, M.; White, A.D.; Sharpe, S.A.; Bechini, J.; Prats, C.; Vilaplana, C.; Cardona, P.-J. Surveillance of Daughter Micronodule Formation Is a Key Factor for Vaccine Evaluation Using Experimental Infection Models of Tuberculosis in Macaques. Pathogens 2023, 12, 236. Nogueira, I.; Català, M.; White, A.D.; Sharpe, S.A.; Bechini, J.; Prats, C.; Vilaplana, C.; Cardona, P.-J. Surveillance of Daughter Micronodule Formation Is a Key Factor for Vaccine Evaluation Using Experimental Infection Models of Tuberculosis in Macaques. Pathogens 2023, 12, 236.

Abstract

Tuberculosis (TB) is still a worldwide major health problem and models using non-human primates (NHP) provide the most relevant approach for vaccine testing. In this study we have 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) have been classified according to their size and we have subclassified small micronodules (<4.4 mm) as ‘isolated’, or as ‘daughter’ when they are in contact with consolidation (described as lesions ≥ 4.5 mm). Our data links 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. This study supports the ‘Bubble Model’ defined with the C3HBe/FeJ mice and proposes a new method to evaluate outcome in experimental models of TB in NHP based on CT images, which would fit a future machine learning approach to evaluate new vaccines.

Keywords

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

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.