a–c, FcγR-humanized mice (n = 6 mice per group for antibody-treated groups; n = 3 for PBS-treated in two independent experiments) were infected with influenza (H1N1 PR8), and FY1 Fc variants were administered intraperitoneally 3 days after infection at the indicated dose. b, c, Weight loss (mean ± s.e.m.) (b) and survival curves (c) of GAALIE-treated mice were compared with the PBS-treated group at the corresponding antibody dose by two-way ANOVA (Bonferroni post hoc analysis adjusted for multiple comparisons) (*P = 0.0456, ^P = 0.041, **P = 0.0014, ^^P = 0.0003, #P = 0.0005, ***P < 0.0001) and log-rank (Mantel–Cox) test, respectively (**P = 0.000911). d–h, The protective activity of LS and GAALIE–LS variants of FY1 was evaluated in a model of antibody-mediated prophylaxis. FcγR/FcRn-humanized mice (n = 8 mice per group for GAALIE–LS at 1.6 and 0.4 mg kg−1; n = 10 for LS at 0.1 mg kg−1, n = 3 for PBS, n = 9 for the remaining treatment groups in two independent experiments) were administered intravenously with the indicated dose of FY1 2 days before influenza challenge (H1N1 PR8). e, f, Weight loss (mean ± s.e.m.) (e) and survival curves (f) of GAALIE–LS-treated mice were compared against the LS group at the corresponding antibody dose by two-way ANOVA (Bonferroni post hoc analysis adjusted for multiple comparisons) (*P < 0.001, ^P = 0.01, #P = 0.02, §P = 0.006, ¶P = 0.002) and log-rank (Mantel–Cox) test, respectively (*P = 0.0283, **P = 0.0266, ***P = 0.00377, ****P = 0.000143). h, The enhanced potency conferred by the GAALIE–LS variant was quantified by plotting the maximum weight change after infection against the serum antibody concentration at the time of challenge. Data were fitted by nonlinear regression analysis (four-parameter, variable slope).