(A) Viral loads after SARS-CoV-2 (MA10) challenge in SARS-CoV-1–vaccinated mice. LOD = 0.007 genomes/g. (B) Viral loads after OC43 challenge in SARS-CoV-2–vaccinated mice. LOD = 27 genomes/g. (C) Viral loads after MHV-1 challenge in OC43-immune mice. (D) Viral loads after MHV-A59 challenge in MHV-1–immune mice. In A–D, mice were intramuscularly primed and boosted after 3 weeks (see Methods). Mice were challenged intranasally 2 weeks after the boost. (E) Viral loads after OC43 challenge in mice that received 50 μL human plasma (before or after vaccination). Plasma was adoptively transferred into naive mice, and on day 1 after transfer, mice were challenged intranasally with OC43. OC43 IgG titers before vaccination (V0) ranged from 12,150 to 109,350, and after vaccination (V1), they ranged from 328,050 to 984,150. (F) OC43 PRNT in plasma before and after vaccination. (G) Viral loads after OC43 challenge in mice that received 50 μL human plasma (pre-2019 vs. COVID-19). Plasma was adoptively transferred into naive mice, and on day 1 after transfer, mice were challenged intranasally with OC43. OC43 IgG titers were 4050 for all pre-2019 samples and 63,450 for all COVID-19 samples. (H) OC43 PRNT in plasma from pre-2019 donors and patients with COVID-19. Lung viral loads were quantified by RT-PCR (A, B, E, and G) or plaque assays (C, D, F, and H). Data are from day 5 after challenge unless otherwise indicated. Dashed lines represent the LOD. A–D data are from 2 independent experiments with 3–5 mice/group. Data in E–H are from 1 experiment with 5 mice/group. Data from all experiments are shown. In A–D, F, and H, error bars indicate the SEM. Panels E and G show paired values. Values below the LOD in log scales represent zero values. *P < 0.05, **P < 0.01, and ***P < 0.001, by nonparametric Mann-Whitney U test (A–D, F, and H) and paired t test (E and G).