Fig. 4: Prophylactic efficacy of neutralizing human monoclonal antibodies against SARS-CoV-2 infection in mouse and NHP models in vivo.
From: Potently neutralizing and protective human antibodies against SARS-CoV-2
a, SARS-CoV-2 challenge model. Mice were treated with anti-IFNAR1 and transduced with AdV-hACE2 followed by the passive transfer of 200 μg of COV2-2196, COV-2130, their combination (1:1 ratio) or an isotype control monoclonal antibody (i.n., intranasal; i.p., intraperitoneal). One day later, mice were inoculated intranasally with SARS-CoV-2. Tissues were collected at 7 dpi for analysis (c, d). b, Body weight change of mice in a with comparison to isotype control using a repeated measurements two-way analysis of variance (ANOVA) with Tukey’s post hoc test. Data are mean ± s.e.m. of each experimental group. The number of mice (n) for each experimental group is shown. c, d, Viral burden (measured as log10(number of genome equivalents (GEQ) per mg)) at 7 dpi in the lungs, spleen and heart (c) and the expression of cytokine and chemokine genes (d) were measured by RT–qPCR assay. Comparisons were performed using a Kruskal–Wallis ANOVA with Dunn’s post hoc test. e, f, MA-SARS-CoV-2 challenge model. Mice were treated with the indicated monoclonal antibody and then inoculated intranasally with MA-SARS-CoV-2. e, Body weight change of mice (mean ± s.e.m. of each experimental group; n = 10 mice per group). f, Viral burden at 2 dpi in the lungs, measured by RT–qPCR (left) or plaque assay (right) from e; comparisons were made using a Kruskal–Wallis ANOVA with Dunn’s post hoc test (n = 10 mice per group). g, Haematoxylin and eosin staining of lung sections from mice that were treated and challenged as in a, shown at day 7. Images are shown at low (left), medium (middle) and high (right) magnification. Each image is representative of two separate experiments (n = 3 to 5 mice per group). Scale bars, 250 μm (left); 50 μm (middle); 25 μm (right). h, i, SARS-CoV-2 NHP challenge model. Rhesus macaques received one 50 mg kg−1 dose of COV2-2196 (n = 4 macaques per group), COV2-2381 (n = 4 macaques per group) or isotype control monoclonal antibody (n = 4 macaques per group) intravenously on day −3 and were then challenged intranasally and intratracheally with SARS-CoV-2 after three days. Subgenomic viral RNA levels were assessed in nasal swabs (h) and bronchioalveolar lavage (i) at multiple time points after challenge. Each black curve shows an individual macaque, with red lines indicating the median values within each treatment group. Data represent a single experiment. Dashed lines indicate the limit of detection (LOD) of the assay.
