Fig. 4: mRNA vaccine induced reduction in replication and pathogenesis of SARS-CoV-2 clones in K18-hACE2 transgenic mice.
From: The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype
a Female K18-hACE2 transgenic mice (7–15 weeks old, n = 8 mice/group) were immunized intramuscularly with a single dose of 1 μg of mRNA-Vaccine Spikevax (Moderna). After 2 weeks the neutralizing antibody titers against SARS-CoV-2 were determined (Supplementary Fig. 10a). Later, mice were intranasally inoculated with 104 TCID50 of SARS-CoV-2D614G, SARS-CoV-2S-Delta, or SARS-CoV-2S-Omicron. Body weight change and clinical scores of the mice were monitored daily. b The mean body weight change is presented (Data from individual animals are shown in Supplementary Fig. 10b). Only the unvaccinated mice infected with SARS-CoV-2D614G and SARS-CoV-2S-Delta showed noticeable weight loss. c Oropharyngeal swabs, lung and nose samples of the infected mice were collected at 2 or 6 days post-infection (dpi) to determine the viral load (n = 4 for each virus). Viral RNA-dependent RNA polymerase (RdRp) gene copies were quantified using probe-specific RT–qPCR. d Infectious virus titers from the lung and nose samples (n = 8 mice/group) were determined using TCID50 assays in VeroE6/TMPRSS2 cells. e Hematoxylin and eosin stain (left panel) and immunohistochemical analysis specific for SARS-CoV-2 nucleocapsid protein (right panel) of lung sections in vaccinated (A) and unvaccinated mice (B) at 2 and 6 dpi following infection with SARS-CoV-2D614G (n = 3), SARS-CoV-2S-Delta (n = 3), and SARS-CoV-2S-Omicron (n = 4). Consolidated lung areas are highlighted with a star, and perivascular and peribronchiolar lymphohistiocytic inflammation highlighted with an arrow. Scale bars, 500 µm. Data are mean ± s.d. from the indicated number of biological replicates. The color key in b also applies to c and d. Statistical significance was determined using two-way ANOVA (a–d) and P-values were adjusted using Tukey’s multiple-comparison test; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Data were obtained from one experiment. Each data point represents one biological replicate. Source data are provided as a Source Data file 4.
