FIG 7.

N1-3-VHHb and N1-3-VHH-Fc, but not N1-5-VHHb and N1-5-VHH-Fc, protect against a challenge with oseltamivir-resistant H5N1 H274Y virus. Twenty-four hours before a challenge with 4 LD₅₀s of NIBRG-14 (N-14)ma or 6 LD₅₀s of H274Y H5N1 virus (H274Y), groups of six BALB/c mice were given 60 μg of N1-3-VHHb, 60 μg of N1-5-VHHb, 60 μg of BL-VHHb, 84 μg of N1-3-VHH-Fc, 84 μg of N1-5-VHH-Fc, 84 μg of N1-7-VHH-Fc, or 84 μg of GP4-Fc. An additional group of six mice was treated with oseltamivir (1 mg/day/kg) starting 24 h before the challenge. (A) Relative body weights. (C) Survival over time after infection. NIBRG-14ma-infected mice treated with N1-3-VHHb, N1-5-VHHb, or oseltamivir survived the challenge. Treatment with N1-3-VHHb rescued all of the H5N1 H274Y mutant-infected mice (***, P < 0.001). (B) Relative body weights. (D) Survival over time after infection. In panels A and B, each datum point represents the average body weight of all of the mice alive and error bars represent standard deviations. Differences between groups were evaluated by two-way ANOVA for the body weight graphs. Kaplan-Meier curves were used for survival analysis (*, P < 0.05; **, P < 0.01; ***, P < 0.001).