Fig. 6: VAED kinetic study: evaluation of lung histopathology.

a Relative lung weight of the left lung lobe, expressed as percentage of the body weight determined at 0 DPI. b Extent of histopathological lesions, expressed as percentage of the total lung area of a slice of the left lung lobe. Two scorings were performed of each slice and the average values were calculated per hamster. c Severity of histopathological lesions, expressed as cumulative (sum) score of 6 different parameters per hamster per time point. Each of the parameters was scored separately. To account for the different scale of the scores, all scores were normalized before calculating the sum. d Severity score for perivascular cuffing of the blood vessels. a–d Symbols show individual values and lines represent the group means; n = 3 per group per timepoint except for a 6 DPI for the mock-vaccinated group (weight of one lung is missing). e–j Representative lung histopathology images (H&E stain). e Lower extent of lung pathology in mock-vaccinated group (4 DPI) compared to f Vaccinated group. g Mild perivascular infiltrates with edema (arrowhead) in mock-vaccinated group (6 DPI) compared to h extensive perivascular infiltrates (arrowheads) in the vaccinated group. i Vaccinated group (8 DPI)—extensive infiltrate around large blood vessel composed of lymphocytes, plasma cells (arrowhead) admixed with granulocytes (arrow) and macrophages. j Mild histopathologic changes in re-challenge group at 8 DPI, composed of thickening alveolar walls (arrowhead) and infiltrates in alveolar lumina (arrow). Level of significance between group means in time in a–d is illustrated with asterisks for the following p values: 0.01 to 0.05 - *; 0.001 to 0.01 - **; 0.0001 to 0.001 - ***; <0.0001 - ****. DPI days post challenge infection.