Fig. 5: NTD/RBD monoclonal antibody combinations offer low-dose in vivo protection and a higher genetic barrier for viral escape.
a, Binding competition to the stabilized trimer as described in Fig. 2a. b, Negative-stain three-dimensional reconstruction of SARS-CoV-2 spike in complex with WRAIR-2025 (NTD) and WRAIR-2173 (RBD) Fabs. c,d, Prophylactic treatment in the K18-hACE2 SARS-CoV-2 mouse model. Antibodies were infused intravenously at a dose of 20 µg (1 mg per kg body weight) or titrated as single mAbs or combinations (1:1 ratio) into groups of mice (n = 15 per group). Mice were challenged intranasally 24 h later with 1.25 × 104 viral particles (1.25 × 104 PFUs) of SARS-CoV-2 (WA1/2020). SARS-CoV-2 viral loads in lung tissue were measured 2 d after challenge in a subset of animals (n = 5 per group) by plaque assay. Bars indicate the mean group value with standard deviation. The remaining mice (n = 10 per group) were assessed daily for weight and clinical symptoms. e, Therapeutic treatment in the K18-hACE2 SARS-CoV-2 mouse model. Antibodies were infused intravenously at the indicated dose 24 h after challenge, performed as indicated above. Mice (n = 15 per group) were assessed daily for weight and clinical symptoms. d,e, For weight loss and viral load in lungs, asterisks indicate significance compared to the ZIKV_MZ4 isotype control group by one-way ANOVA with Dunnett’s multiple-comparisons test. Survival curves were compared individually to the isotype control using a Mantel–Cox log-rank test. For all analysis, ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.5; NS, P > 0.5. f, Viral titers of a replicative rVSV/SARS-CoV-2/GFP virus obtained after two passages in the presence of single mAbs or combinations. Plotted are the means from two independent experiments.
