Fig. 5. mACE2-CAR_sIL15 NK cells protect against live SARS-CoV-2 infection in the K18-hACE2 humanized mouse model.

a Scheme for in vivo studies using K18-hACE2 humanized transgenic mice. b K18-hACE2 humanized transgenic mice were infected with 1 × 10³ plaque-forming units (PFU) of SARS-CoV-2 prior to being treated with the vehicle (PBS), control tEGFR NK cells, or mACE2-CAR_sIL15 NK cells. Survival of mice is summarized. N = 5 mice/group. P values were determined by Kaplan–Meier survival analysis and calculated by the Gehan-Breslow-Wilcoxon test (two-sided). c Viral RNA levels are shown for brain and lung tissues of mice infected i.n. with 1 × 10³ plaque-forming units (PFU) of SARS-CoV-2. N = 5 mice/group. P values were determined by one-way ANOVA with multiple comparisons and adjusted by the Holm-Sidak method. Data are presented as mean ± SEM. d Representative images of the three groups in b show immunohistochemistry (IHC) staining of coronavirus nucleocapsid protein (NP). Scale bars, 400 μm. e Release assay of various cytokines into plasma of K18-hACE2 transgenic mice. Mice were infected with 1 × 10³ PFU of live SARS-CoV-2 prior to being treated with the vehicle (PBS), control tEGFR NK cells, control sIL15 NK cells, or mACE2-CAR_sIL15 NK cells. Four days later, all mice were sacrificed to collect blood plasma to measure levels of the indicated cytokines by a cytokine release Luminex assay. N = 4 mice/group. Data are presented as an average of two replicates for each mouse. Source data are provided as a Source Data file.