Fig. 2: CoV-X2 protects mice transduced with AAV-hACE2 against SARS-CoV-2 disease.
From: Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice
a, Body weight over time in mice infected with SARS-CoV-2. We transduced 13–15-week-old C57BL/6NCrl wild-type female mice with AAV-hACE2 by forced inhalation, delivering viral particles to the upper and lower respiratory tract. After >7 days, mice were infected with SARS-CoV-2 (1 × 104 plaque-forming units (PFU)) or received vehicle by the intranasal route. Weight was monitored daily for 8 days (SARS-CoV-2, n = 5; control, n = 4). Mean with s.d. b, Kinetics of viral burden in lungs of mice infected with SARS-CoV-2 (n = 5) by plaque assays. Mean with s.d. Dashed line, limit of detection. c, Kinetics of viral RNA levels in lung samples from mice infected with SARS-CoV-2 (n = 5) by quantitative PCR with reverse transcription (RT–qPCR). Mean with s.d. d, Wild-type mice were transduced with AAV-hACE2 by forced inhalation. After >7 days, mice were inoculated intraperitoneally with antibodies one day before (black arrow) or 12 h after (red arrow) being infected intranasally with SARS-CoV-2 (1 × 104 PFU). e, f, Body weight was monitored daily in mice treated 24 h before infection (e, C121, n = 9; C135, n = 5; CoV-X2, n = 13; isotype control, n = 10) or 12 h after infection (f, CoV-X2, n = 4; control, n = 10). Mean with s.d. is shown. g, Lung viral burden by plaque assay at 2 dpi (isotype control, n = 8; CoV-X2, n = 5; C121, n = 5; C135, n = 5) and 5 dpi (isotype control, n = 6; CoV-X2, n = 10; C121, n = 5; C135, n = 5). The dashed line indicates the limit of detection; mean with s.d. P value was calculated with two-tailed Student’s t-test. h, Viral RNA levels in the spleen by RT–qPCR at 5 and 8 dpi (isotype control, n = 6 or 8 (indicated by dots); CoV-X2, n = 8 or 10 (indicated by dots)). Mean with s.d. P value, two-tailed Student’s t-test. i, Photographs of lungs from infected mice (8 dpi). j, Histopathology and F4/80 immunohistochemistry (IHC). Haematoxylin and eosin (H&E)-stained sections of paraffin-embedded lungs from infected mice (8 dpi). Arrowheads, foamy macrophages. F4/80 IHC shows abundant macrophage infiltration in lungs of mice treated with isotype control, but not those with CoV-X2. Each image representative of two separate experiments (n = 3–5 mice per group). Scale bars, 20 μm (inset in H&E), 50 μm (H&E right, F4/80 IHC), 100 μm (H&E middle), 1 mm (H&E, left).
