Figure 2.

Nasally delivered IFN-λ2 treatment protects K18-hACE2 mice against SARS-CoV-2 infection

(A–D) Eight-week-old female K18-hACE2 mice were inoculated by intranasal route with 10³ FFU of WA1/2020 D614G. At D-2 (A and B) or D+1 and D+2 (C and D), mice were given a single 2-μg dose of murine IFN-λ2 or PBS by the intranasal route.

(A and C) Viral RNA levels were measured at 3 dpi.

(B and D) Infectious virus was measured at 3 dpi (A and B: n = 9 per group, 2 experiments; C and D: n = 8 per group, 2 experiments).

(E) Hematoxylin and eosin staining of lung sections from animals treated with 2-μg doses of murine IFN-λ2 or PBS by intranasal route at -16 h and +8 h relative to inoculation with WA1/2020 D614G and harvesting at 7 dpi. Low (top, scale bars, 500 μm) and high (bottom, scale bars, 100 μm) power images are shown. Representative images are from n = 5 per group except naive (n = 2).

(F) Quantitation of hematoxylin⁺ area as an index of cellularity in lung sections in (E).

(G) Eight-week-old female K18-hACE2 mice were treated with 2 μg of murine IFN-λ2 or PBS at -16 h and challenged with 10³ FFU of WA1/2020 D614G. Heatmaps of cytokine levels in lung homogenates at 3 dpi. Fold change was calculated relative to mock-infected mice, and log₂ values are plotted (2 experiments, n = 7 per group except naive [n = 4]).

(H–K) Five-month-old female K18-hACE2 mice were inoculated with 10³ FFU of B.1.1529 Omicron variant. At D-1 (H and I) or D+1 and D+2 (J and K), mice were given 2 μg of murine IFN-λ2 or PBS by the intranasal route. Viral RNA (H–J) and infectious (I–K) virus levels were measured at 3 dpi (H and I: n = 7–8 per group, 2 experiments; J and K: n = 6–7 per group, 2 experiments).

Bars (A–D and G–J) indicate median values. Data were analyzed by Mann-Whitney tests (A–D and H–K) (^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, and ^∗∗∗∗p < 0.0001).

See also Figures S1, S2, and S3.