Seven-week-old female K18-hACE2 transgenic mice were immunized with 5 or 0.1 μg of mRNA vaccines as described in Fig 1A. Five weeks after completing a primary vaccination series, mice were challenged with 104 focus-forming units (FFU) of WA1/2020 D614G or B.1.1.529. A-B. Body weight change in animals immunized with 5 μg (A) or 0.1 μg (B) of control or mRNA-1273 vaccines between days 0 and 6 after challenge with WA1/2020 D614G or B.1.1.529. Data show mean values (n = 7–8, two experiments). C-H. Viral burden at 6 dpi in the nasal washes (C, F), nasal turbinates (D, G), and lungs (E, H) as assessed by qRT-PCR of the N gene after WA1/2020 D614G or B.1.1.529 challenge of mice immunized with 5 μg (C-E) or 0.1 μg (F-H) of control or mRNA-1273 vaccines (n = 7–8, two experiments, boxes illustrate median values, dotted lines show LOD). Statistical analyses: A-B, unpaired t test; C-H: Mann-Whitney test (ns, not significant; * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001). I. Correlation analyses comparing serum neutralizing antibody concentrations three weeks after the second vaccine dose and lung viral titers (6 dpi) in K18-hACE2 mice after challenge with WA1/2020 D614G (left panel) or B.1.1.529 (right panel); Pearson’s correlation R2 and P values are indicated as insets; closed symbols 5 μg vaccine dose; open symbols, 0.1 μg vaccine dose.