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. 2023 May 30;120(23):e2303509120. doi: 10.1073/pnas.2303509120

Fig. 2.

Fig. 2.

Vectored immunoprophylaxis by decoy-expressing AAV decoy vector and therapeutic use. (A) The experimental scheme for testing decoy prophylaxis is diagrammed. hACE2 K18 Tg and Balb/c mice were treated by i.v. injection or i.n. instillation with decoy-expressing AAV vector or control GFP.nLuc-expressing AAV vector (1 × 1012 vg). Three days posttreatment, the hACE2 K18 Tg mice were challenged with SARS-CoV-2 WA1/2020 and the Balb/c mice were challenged with Omicron variants (2 × 104 PFU). Viral RNA copies were quantified 2 d (Omicron) or 3 d (SARS-CoV-2 WA1/2020) postinfection. (B) Mice (n = 3 to 4) were treated with decoy-expressing or control GFP-expressing AAV vectors and challenged with SARS-CoV-2 WA1/2020. Viral RNA copies in the lungs were quantified 3-dpi. (C) H&E-stained lung sections from control and decoy-expressing AAV vectors and SARS-CoV-2-infected mice are shown on the left (2×, scale bars 500 μm) and with the boxed area enlarged on the right (20×, scale bars 50 μm). (D) Mice (n = 3) were treated with decoy-expressing AAV vectors on day 0 and challenged with SARS-CoV-2 WA1/2020 on day 3. Body weight was measured daily. (E) Balb/c mice (n = 3 to 4) were treated with decoy-expressing or GFP-expressing control AAV vectors and then infected 3 d later with Omicron BA.1, BA.2, or BA.5. Viral RNA copies in the lungs were quantified 2-dpi. (F) Mice (n = 4) were administered decoy-expressing AAV vectors i.m. or i.v. and challenged 3-dpi with SARS-CoV-2 WA1/2020. (G) hACE2/IFNAR KO mice (n = 4) were administered decoy-expressing AAV2.retro vector i.m. or i.n. and then infected 3 d later with SARS-CoV-2 WA1/2020. Viral RNA copies in the lungs were quantified 3-dpi. (H) Therapeutic use of the decoy-expressing AAV vectors was tested as diagrammed (Left). hACE2 K18 Tg (n = 4) were infected with SARS-CoV-2 WA1/2020 (2 × 104 PFU) and then treated with decoy-expressing AAVs at time-points up to 48 h postinfection. Viral RNA in the lung was quantified 3-dpi (Right). CIs are shown as mean ± SD. ***P ≤ 0.001, ****P ≤ 0.0001.