Fig. 4: Protection of K18-hACE2 mice from BA.5 challenge after boosting with clinically representative versions of mRNA-1273, mRNA-1273.214 and mRNA-1273.222.
Seven-week-old female K18-hACE2 mice were immunized with 0.25 μg of control mRNA or mRNA-1273; boosted 31 weeks later with PBS, 0.25 μg of control mRNA or 0.25 μg of clinically representative versions of mRNA-1273, mRNA-1273.214 or mRNA-1273.222 vaccines; and then, 1 month later, challenged via intranasal route with 104 FFU of BA.5. a, Viral RNA levels at 4 dpi in the nasal washes, nasal turbinates and lungs. b, Infectious viral load at 4 dpi in the lungs after BA.5 challenge of vaccinated and boosted mice as determined by plaque assay (a,b: n = 8 for mRNA-1273.214, n = 9 for control mRNA and mRNA-1273 and n = 10 for PBS and mRNA-1273.222, two experiments; tops of boxes illustrate mean values, and dotted lines show LOD based on tissue weight or volume). c, Cytokine and chemokine levels in lung homogenates at 4 dpi. Data are expressed as fold change relative to naive mice, and log2 values are plotted (n = 8 for mRNA-1273.214, n = 9 for control mRNA and mRNA-1273, n = 10 for PBS and mRNA-1273.222 and n = 4 for naive, two experiments; lines illustrate median values, and dotted lines indicate LOD for each respective analyte based on a standard curve). Measurements are also shown in Supplementary Table 1. d, Hematoxylin and eosin staining of lung sections harvested at 4 dpi from mice immunized with control mRNA (CTRL-mRNA) or mRNA-1273 (primary two dose series) and then boosted with PBS, mRNA-1273, mRNA-1273.214 or mRNA-1273.222 vaccines. An uninfected (naive) animal is shown for comparison. Low (top: scale bars, 1 mm), moderate (middle: scale bars, 200 µm) and high (bottom: scale bars, 50 µm) power images are shown. Representative images of multiple lung sections from n = 2 for each group, two experiments. Statistical analysis. a–c, One-way Kruskal–Wallis ANOVA with Dunn’s multiple comparisons post test; comparisons are between all groups. Exact P values are indicated, and only significant comparisons are shown. Primary data are provided as a Source Data file.
