To determine whether the in-vitro neutralizing activity displayed by PN-SIA49 would be predictive of its protective efficacy in-vivo, BALB/c mice were inoculated intranasally with 3 fifty percent lethal dose (LD50) of A/Wilson Smith/33(H1N1) (WS33) or A/Vietnam/1203/2004 (H5N1) (VN04) virus, and were treated 24 hours later with 10, 1 or 0.1 mg/kg of PN-SIA49. An anti-HCV/E2 mAb (e137) [28] was used as control at 10 mg/ kg. PN-SIA49 protected mice from lethal challenge with WS33 in a dose-dependent manner providing 100% protection (6/6) against death in animals that received 10 mg/kg of the antibody and 83.3% protection (5/6) in animals that received 1 mg/kg ( Figure 1C ). Consistent with the in-vitro neutralizing activity, PN-SIA49 at 10 mg/kg afforded 66.6% protection against lethal H5N1 virus challenge ( Figure 1D ) whereas control mice rapidly succumbed to infection by day 8 post-challenge (p.c.). Surviving mice remained healthy and showed minimal body weight loss (maximum weight loss: 7.2% in WS33 group, 14.4% in VN04 group) over the 2-week observation period. At the conclusion of the experiment, The mean body weight loss was 2.2% in the treated mice challenged with VN04 virus ( Figure 1B ) while mice infected with WS33 regained their full body weight ( Figure 1A ).