Fig. 5: Human monoclonal recombinant antibodies as prophylactic and therapeutic interventions affect disease outcome.

a, Viral titers measured by PFU in homogenized lung tissue at 4 dpi in MISTRG6-hACE2 mice that received prophylactic treatment of convalescent patient plasma or were left untreated. Paired, two-tailed t-test. Untreated controls: n = 6 convalescent treated group and n = 4 biologically independent mice examined over two independent experiments. Individual values for each mouse and means are presented. b, Human immune cells at 4 dpi in lungs of MISTRG6-hACE2 mice that received prophylactic treatment of convalescent patient serum or were left untreated. Paired, two-tailed t-test. Untreated controls: n = 6 convalescent treated group and n = 4 biologically independent mice examined over two independent experiments. Individual values for each mouse and means are presented. c, Human macrophages (hCD45⁺hCD68⁺) at 4 dpi in lungs of MISTRG6-hACE2 mice that received prophylactic treatment of convalescent patient serum or were left untreated. Paired, two-tailed t-test. Untreated controls: n = 6 convalescent treated group and n = 4 biologically independent mice examined over two independent experiments. Individual values for each mouse and means are presented. d, Viral RNA and viral titers measured by PFU in homogenized lung tissue at 4 dpi in MISTRG6-hACE2 mice that received prophylactic treatment of monoclonal antibody clone 135 (m135) or clone 144 (m144) 8 h before infection or were left untreated (untd). n = 6. Mann–Whitney, two-tailed test was used for comparison of viral RNA. One-sample Wilcoxon signed-rank test was used to determine significance in the viral titer quantification (effect size = 0.9, W = 21). e, Human immune cells in lungs of MISTRG6-hACE2 mice received a prophylactic treatment of monoclonal antibody clone 135 (m135) or clone 144 (m144) 8 h before infection or were left untreated (untd). n = 6 biologically independent mice examined over two independent experiments. Individual values for each mouse and means are presented. Unpaired t-test, two-tailed. f, Human immune cells in BAL of MISTRG6-hACE2 mice that received a prophylactic treatment of monoclonal antibody clone 135 (m135) or clone 144 (m144) 8 h before infection or were left untreated (untd). Untreated control n = 4 and treated group n = 5 biologically independent mice examined over two independent experiments. Individual values for each mouse and means are presented. Unpaired t-test, two-tailed. g, Human immune lineages in lungs and BAL of mAb-treated or untreated mice at 4 dpi within the human CD45⁺ population. Classical monocytes (CD14⁺), intermediate monocytes (CD14⁺CD16), non-classical monocytes (CD16⁺CD14⁻), macrophages (CD68⁺), NK cells (NKP46⁺), T cells (CD3⁺) and B cells (CD19⁺ and/or CD20⁺). MISTRG6-hACE2 mice received a prophylactic treatment of monoclonal antibody clone 135 (m135) or clone 144 (m144) 8 h before infection or were left untreated (untd). In lungs, n = 6 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are presented. In BAL, untreated control n = 4 and treated group n = 5 biologically independent mice examined over two independent experiments. Individual values for each mouse and means are presented. Unpaired t-test, two-tailed. Statistical significance was deemed by comparison to uninfected group. P values are represented by: NS P > 0.05; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001. Only changes in frequencies of lung macrophages (m135 P = 0.029, m144 P = 0.037) and BAL macrophages (m144 P = 0.0042) and monocytes (CD16⁺ (m135 P = 0.0051, m144 P = 0.0058)) were statistically significant. h, Human macrophages (hCD45⁺hCD68⁺) at 4 dpi in lungs and BAL of MISTRG6-hACE2 mice that received prophylactic treatment of mAbs (clone 135 or 144) or were left untreated. Lungs: untreated control n = 6 and treated group n = 5 biologically independent mice examined over three independent experiments. BAL: untreated control n = 5 and treated group n = 4 biologically independent mice examined over two independent experiments. Individual values for each mouse and means are presented. Unpaired t-test, two-tailed. i, Weight change in mAb-treated mice (prophylaxis) at 2 dpi and 4 dpi plotted as percent change compared to original weight measured just before inoculation with SARS-CoV-2. n = 6 biologically independent mice examined over two independent experiments. Repeated-measures one-way ANOVA with Dunnett’s multiple comparison test comparing weight change at 4 dpi to untreated group was used. P value for m144 = 0.01 and P value for m135 = 0.98. Individual values for each mouse and means are presented. j, Viral RNA and viral titers measured by PFU in homogenized lung tissue at 4 dpi in MISTRG6-hACE2 mice that received post-infection treatment of a mixed cocktail of monoclonal antibodies clone 135 (m135) and clone 144 (m144) or were left untreated (untd). Early treatment groups were treated at 11 hpi, and late treatment groups were treated at 35 hpi. Mann–Whitney, two-tailed test was used for comparison of viral RNA. One-sample Wilcoxon signed-rank test was used to determine significance in the viral titer quantification (effect size = 0.9, W = 21). Untreated control n = 6 and early and late treated groups n = 5 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are presented. k, Human immune cells in lungs of MISTRG6-hACE2 mice that received early, late or no treatment of monoclonal antibody mix. Untreated control n = 6 and early and late treated groups n = 5 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are presented. Unpaired, two-tailed t-test. P values <0.05 are plotted. l, Human immune cells in BAL of MISTRG6-hACE2 mice that received early, late or no treatment of monoclonal antibody mix. Untreated control n = 4 and early and late treated groups n = 5 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are presented. Unpaired, two-tailed t-test. P values <0.05 are plotted. Untreated control n = 6 and early and late treated groups n = 5 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are presented. m, Weight change upon mAb therapeutic treatment at 2 and 4 dpi plotted as percent change compared to original weight measured just before inoculation with SARS-Cov-2. n = 6 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are presented. One-way ANOVA (Sidak’s multiple comparisons test) comparing weight change at 4 dpi to untreated group was used. Early treatment versus untreated P = 0.8 and late treatment versus untreated P = 0.49. n, Human immune lineages in lungs and BAL of mAb-treated (early or late) or untreated mice at 4 dpi within the human CD45⁺ population. Classical monocytes (CD14⁺), intermediate monocytes (CD14⁺CD16), non-classical monocytes (CD16⁺CD14⁻), macrophages (CD68⁺), NK cells (NKP46⁺), T cells (CD3⁺) and B cells (CD19⁺ and/or CD20⁺). MISTRG6-hACE2 mice were therapeutically treated with mAb mix early at 11 hpi or late at 35 hpi. Lung: untreated control n = 6 and early and late treated groups n = 5 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are presented. BAL: untreated control n = 4 and early and late treated groups n = 5 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are presented. Statistical significance was deemed by unpaired t-test compared to uninfected group. P values are represented by: NS P > 0.05; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001. Only changes in frequencies of monocytes (CD14⁺CD16⁺) were statistically significant (P = 0.01). Means with s.d. are plotted. In Fig. 5, MISTRG6 mice were engrafted with CD34⁺ cells neonatally isolated from at least two donors. Pooled or infection matched representative results of at least two independent experiments are presented. Only P values <0.05 are shown. Mean with s.d. or individual values are plotted. N.D., not detected; NS, not significant.