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P80

Surveillance of daughter micronodules is a key factor to evaluate vaccines at the tuberculosis experimental infection in macaques.

I Nogueria(6) M Català(2,3) A D White(4) S S Sharpe(4) J Bechini(6) C Prats(3) C Vilaplana(5,8) P J Cardona(1,2,5,7,8)

1:Microbiology Department. Hospital Universitari Germans Trias i Pujol - IGTP; 2:Comparative Medicine and Bioimage Center of Catalonia (CMCiB). IGTP; 3:Escola d'Enginyeria Agroalimentària i de Biosistemes de Barcelona Departament de Física, Universitat Politècnica de Catalunya (UPC)-BarcelonaTech; 4:Public Health England, National Infection Service, Porton Down, Salisbury; 5:Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES); 6:Radiology Department. Hospital Universitari Germans Trias i Pujol - IGTP; 7:Genetics and Microbiology Department, Universitat Autònoma de Barcelona; 8:Experimental Tuberculosis Unit. Institut Germans Trias i Pujol (IGTP)

Tuberculosis (TB) is still a worldwide major health problem that has been aggravated with the COVID19 outbreak. There is an urgent need for developing experimental models able to have a good predictive value for vaccine testing. The use of non-human primates (NHP) to develop experimental tuberculosis is considered the better approach. The use of computed tomography (CT) allows a careful monitoring of the lesions in the progress of the pulmonary infection. In this study we have analysed CT images for cynomolgus and rhesus macaques infected with a low dose aerosol of Mycobacterium tuberculosis (Mtb) monitored for 16 weeks, to evaluate the impact of intradermal and aerosol BCG vaccination in the progression of the disease. All lesions (2553 from 35 macaques) have been classified according to the measure of its major axis. We have differentiated micronodules ([removed]4.5 mm). Our data links the higher capacity to contain Mtb infection in Cynomolgus with its capacity to reduce the presence of daughter micronodules, thus avoiding the development of consolidated lesions and its enlargement and reducing the cavitation process. In the case of rhesus, intradermal vaccination has a higher capacity to reduce daughter micronodules compared with aerosol vaccination. This study supports the “bubble model” characterized with the C3HBe/FeJ mice and proposes a new method to evaluate experimental models of TB in NHP based on CT images, which would fit a future machine learning approach to evaluate new vaccines.

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