Fig. 3: VAED model development study: lung (histo)pathology.

a Relative lung weight of the left lung lobe, expressed as percentage of the body weight determined on −1 DPI. Within-group changes between −1 and 5 DPI were significant (not annotated). b Extent of histopathological lesions, expressed as percentage of the total lung area of a section of the whole left lung lobe. Three scorings were performed of each slice and the average values were calculated per hamster. c Severity of histopathological lesions, expressed as the cumulative (sum) of scores for six separate parameters per hamster per time point. To account for the different scale of the scores, all scores were normalized before calculating the sum. a–c Symbols show individual values and bars illustrate group means, n = 4 per group except for group 1x high dose on 13 DPI, where n = 3. Error bars: 95% CI. Significant differences between groups are 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 - ****; ns not significant (≥0.05). DPI days post challenge infection. d Mock-vaccinated group with mild extent of lung pathology (grade 1–2), often centered around bronchioles; e 1x high dose vaccinated group with extensive and coalescing lung histopathology (grade 3); f Mock-vaccinated group: alveolar lumina containing macrophages and granulocytes (arrow); g 1x high dose group: coalescing lung changes with prominent perivascular infiltrates (arrowhead); h 1x high dose group: extensive type II pneumocyte proliferation (arrow) with alveolar hemorrhage (arrowhead); i 1x high dose group: perivascular infiltrates with more than 5 layers of cells (arrowhead), grade 3 blood vessel change; d–i Representative images from 5 DPI.