Figure 4.
Prophylactic treatment with CV3-1 protects mice from lethal SARS-CoV-2 infection
(A) Experimental design to test in vivo efficacy of NAbs CV3-1 and CV3-25 administered alone (12.5 mg/kg body weight) or as a 1:1 cocktail (6.25 mg/kg body weight each) 1 day prior to challenging K18-hACE2 mice (i.n.) with SARS-CoV-2-nLuc followed by non-invasive BLI every 2 days. Human IgG1-treated (12.5 mg/kg body weight) mice were the control cohort (Iso).
(B) Representative BLI images of SARS-CoV-2-nLuc-infected mice in ventral (v) and dorsal (d) positions.
(C and D) Temporal quantification of nLuc signal as flux (photons/s) computed non-invasively in whole body (C) or brain (D).
(E) Temporal changes in mouse body weight with initial body weight set to 100%.
(F) Kaplan-Meier survival curves of mice statistically compared by log-rank (Mantel-Cox) test.
(G and H) Ex vivo images of organs and nLuc signal quantified as flux (photons/s) after necropsy.
(I) Viral loads (nLuc activity/mg tissue) measured in Vero E6 cells as targets. Non-detectable virus amounts were set to 1.
(J and K) Fold changes in cytokine mRNA expression in lung and brain tissues. Data were normalized to Gapdh mRNA.
Viral loads (I) and inflammatory cytokine profile (J and K) were determined after necropsy for mice that succumbed to infection at 6 dpi and in mice surviving at 22 dpi.
Scale bars in (B) and (G) denote radiance (photons/s/cm2/steradian). Each curve in (C–E) and each data point in (H–K) represents an individual mouse. Data in (B–K) are from two independent experiments, and n = 4–6 per group Grouped data in (C–K) were analyzed by 2-way ANOVA followed by Dunnett’s or Tukey’s multiple comparison tests. Statistical significance for group comparisons to isotype control are shown in black and for those to CV3-25 are shown in red. ∗, p < 0.05; ∗∗, p < 0.01; ∗∗∗, p < 0.001; ∗∗∗∗, p < 0.0001. Mean values ± SD are depicted.