In vivo therapeutic activity of potent SARS-CoV-2 neutralizer Cv2.1169. (A) Schematic diagram showing the experimental design of Cv2.1169 antibody therapy in SARS-CoV-2–infected K18-hACE2 mice (top). Animals were infected i.n. with 10⁴ PFU of SARS-CoV-2 and 6 h later received an i.p. injection of Cv2.1169 or isotypic control IgG antibody at ∼10 mg/kg (0.25 mg) and ∼20 mg/kg (0.5 mg). Graphs showing the evolution of initial body weight (% Δ weight, bottom left) and survival rate (bottom right) in animal groups. Groups of mice were compared in the Kaplan-Meier analysis using log-rank Mantel-Cox test. (B) Same as in A but with K18-hACE2 mice infected with 10⁵ PFU and treated 22 h later with 1 mg i.p. of Cv2.1169 IgG antibody (∼40 mg/kg). (C) Same as in A but with infected mice treated with Cv2.1169 IgG and IgA antibodies at ∼5 mg/kg (0.125 mg). (D) Schematic diagram shows the experimental design of Cv2.1169 antibody therapy in SARS-CoV-2–infected golden Syrian hamsters (top). Animals (seven or eight per group) were infected i.n. with 6 × 10⁴ PFU of SARS-CoV-2 and 24 h later received an i.p. injection of PBS, Cv2.1169 or isotypic control IgG antibody at ∼10 mg/kg (1 mg). Dot plots showing LW/BW ratio × 100 (left), infectivity (center), and RNA load (right) measured in animal groups at 5 dpi. Groups of hamsters were compared using two-tailed Mann-Whitney test. (E) Same as in D but with infected animals treated 4 h later with Cv2.1169 IgG and IgA antibodies at ∼5 mg/kg (0.5 mg). (F) Same as in A but with K18-hACE2 mice infected with 10⁴ PFU of the SARS-CoV-2 variant β (B.1.351), and either pre-treated 6 h before infection with ∼10 mg/kg (0.25 mg) of Cv2.1169 IgA or treated 6 h after infection with ∼10 mg/kg (0.25 mg) of Cv2.1169 IgG or isotype control (ctr).