Fig. 5: Histopathological analysis of SARS-CoV-2 infection in NVX-CoV2373-immunized mice transduced with Ad/hACE2 and challenged with SARS-CoV-2.

Groups of mice (N = 10/group) were immunized with NVX-CoV2373 with or without Matrix-M (5 μg) with two doses spaced 14 days apart. Placebo group received formulation buffer. Following immunization, mice were intranasally transduced with Ad/CMV/hACE2, 52 days after the first priming dose. At 4 days post transduction, mice were challenged with 1 × 10⁵ pfu/mouse of SARS-CoV-2 (WA1 strain). Lungs were collected 4 and 7 days post infection. Representative placebo control animal at 4 days post infection showing denuding of bronchial epithelium with marked thickening of the alveolar septa surrounded by mixed inflammatory cells. Diffuse perivascular cuffing was observed throughout the lung, consisting of neutrophils and macrophages. At 7 days post infection, peribronchiolar inflammation and perivascular cuffing was markedly increased. Lungs from NVX-CoV2373-vaccinated animals had little or no epithelial cell sloughing or infection within large and small bronchi at days 4 and 7 post infection. There was no evidence of exacerbated lung inflammation in NVX-CoV2373-immunized animals. Images from age- and sex-matched BALB/c mice from a separate experiment that were transduced with Ad/hACE2 alone as a control are shown in the right panel at 7 days post transduction. Scale bar 100 μm.