Surveillance of Daughter Micronodule Formation Is a Key Factor for Vaccine Evaluation Using Experimental Infection Models of Tuberculosis in Macaques
Nogueira, Isabel (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Català, Martí (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
White, Andrew D. (National Infection Service (Salisbury, Regne Unit))
Sharpe, Sally A. (National Infection Service (Salisbury, Regne Unit))
Bechini Bernad, Jordi (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Prats, Clara (Universitat Politècnica de Catalunya. Departament de Física)
Vilaplana, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Cardona, Pere-Joan (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Date: |
2023 |
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. |
Rights: |
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Language: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Subject: |
Tuberculosis ;
BCG vaccine ;
Aerosol vaccination ;
Non-human primate ;
Macaque ;
Bubble model ;
Computed tomography scanner |
Published in: |
Pathogens, Vol. 12 (february 2023) , ISSN 2076-0817 |
DOI: 10.3390/pathogens12020236
PMID: 36839508
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Record created 2023-03-02, last modified 2024-05-02