Surveillance of Daughter Micronodule Formation Is a Key Factor for Vaccine Evaluation Using Experimental Infection Models of Tuberculosis in Macaques.
Isabel Nogueira, Mart�� Catal��, Andrew D White, Sally A Sharpe, Jordi Bechini, Clara Prats, Cristina Vilaplana, Pere-Joan Cardona
Author Information
Isabel Nogueira: Radiology Department, 'Germans Trias i Pujol' University Hospital, 08916 Badalona, Spain.
Mart�� Catal��: Comparative Medicine and Bioimage Centre of Catalonia (CMCiB), Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain. ORCID
Andrew D White: UK Health Security Agency, Porton Down, Salisbury SP4 0JG, UK. ORCID
Sally A Sharpe: UK Health Security Agency, Porton Down, Salisbury SP4 0JG, UK.
Jordi Bechini: Radiology Department, 'Germans Trias i Pujol' University Hospital, 08916 Badalona, Spain.
Clara Prats: Escola d'Enginyeria Agroaliment��ria i de Biosistemes de Barcelona Departament de F��sica, Universitat Polit��cnica de Catalunya (UPC)-BarcelonaTech, 08860 Castelldefels, Spain. ORCID
Cristina Vilaplana: Unitat de Tuberculosi Experimental, Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain. ORCID
Pere-Joan Cardona: Unitat de Tuberculosi Experimental, Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain. ORCID
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 (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.
