Three- to 4-week-old male and female hSTAT2 KI mice were administered 200 μg of the indicated murine (a, b) or human (c, d) mAbs and inoculated subcutaneously with 105 FFU of ZIKV. Viral burden was assessed at 9 dpi in the spleen (a, c) and brain (b, d). a, b Isotype control, n = 33; Z12, n = 8; Z13, n = 10; Z11, n = 10; Z15, n = 10; Z17, n = 9; Z18, n = 15; Z14, n = 10; Z16, n = 10; Z20, n = 9. c, d Isotype control, n = 27; 749-A4, n = 11; 749-A4 LALA, n = 11; ZIKV-231, n = 11; ZIKV-231 LALA, n = 11; ZIKV-292, n = 15; ZIKV-292 LALA, n = 11. Data are pooled from at least two experiments (Kruskal–Wallis one-way ANOVA with Dunn’s post-test comparison between the indicated groups; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001; a Z11, p = 0.002; b Z11, p = 0.015; Z15, p = 0.006; Z17, p = 0.003; c isotype vs. 749-A4, p = 0.0001; ZIKV-231 vs. ZIKV-231 LALA, p = 0.004; d isotype vs. ZIKV-231, p = 0.039; isotype vs. ZIKV-292, p = 0.012; isotype vs. 749-A4, p = 0.013; ZIKV-231 vs. ZIKV-231 LALA, p = 0.004; ZIKV-292 vs. ZIKV-292 LALA, p = 0.003; 749-A4 vs. 749-A4 LALA, p = 0.013). Dotted lines denote the limit of detection (LOD) of the assay. e–h Four- to 5-week-old male C57BL/6J mice administered 1 mg of an anti-Ifnar1-blocking mAb and 500 μg of the indicated murine (e, f) or human (g, h) mAbs. The following day, mice were inoculated subcutaneously with ZIKV and mortality (e, g) and weights (f, h) were tracked. Data are representative of two experiments and survival analysis was performed using the Mantel–Cox log-rank test with Bonferroni correction compared to the isotype group (e isotype, n = 13; Z15, n = 14, p = 0.052; Z17, n = 14, p = 0.018; Z18, n = 14, p = 0.089; g: isotype, n = 16; ZIKV-292, n = 16, p = 0.026; 749-A4, n = 16, p < 0.002). In the figure: *p < 0.05, **p < 0.01. Weights were analyzed by two-way ANOVA with Dunnett’s post-test comparison to isotype-treated animals (*p < 0.05; f Z15: day 10, p = 0.037; Z17: day 8, p = 0.037; day 9, p = 0.009; day 10, p = 0.002; day 11, p = 0.006; h 749-A4: day 9, p = 0.014; day 10, p = 0.005; ZIKV-292: day 16, p = 0.045; day 18, p = 0.037; day 20, p = 0.027); error bars represent the mean values ± SD. Source data are provided as a Source Data file for Figs. 1f, h.