Protection assay of neutralizing mAbs was performed with ICR strain 2-day-old suckling mice [41] . Mice were inoculated intracerebrally with 20 ml of DENV-2-mAb mixture containing 1610 4 pfu (25-fold LD 50 ) of DENV-2 with neutralizing mAbs at concentrations of 1, 10 or 100 mg/ml. Generally, the nonneutralizing antibody normal mouse IgG (NMIgG) treated group showed paralysis, ruffling, and slowing of activity around 6 to 9 days. This was followed by severe sickness leading to anorexia, asthenia and death within 9 to 17 days ( Figures 2B and 2C) . In contrast, mAbs DB32-6 at a concentration of 10 mg/ml protected 93% of the mice from the lethal challenge of DENV-2 ( Figure 2B ). mAbs 3H5, DB23-3, DB2-3 and DB25-2 had survival rates of Humanized mAb against Dengue Virus www.plosntds.org 75%, 76%, 72% and 71%, respectively. DB42-3 and DB13-19 had survival rates of 46% and 28%, respectively ( Figure 2B ). The neutralizing mAbs showed a significant delay of the onset of paralysis and death relative to the NMIgG. To evaluate the therapeutic potential of the highly protective mAb DB32-6, we administered 100 mg/ml or 1 mg/ml to infected suckling mice. The survival rates for DB32-6 at 100 mg/ml or 1 mg/ml were 100% and 89%, respectively ( Figure 2C ). In comparison, 3H5 showed 82% and 40% survival rates at 100 mg/ml or 1 mg/ml, respectively. Stat1 2/2 mice, which lack a transcription factor involved in interferons (IFNs) signaling were sensitive to lethality induced by DENV-2 infection [27, 31] . To test the potential therapeutic effects of the strongest neutralizing mAb DB32-6, we challenged Stat1 2/2 mice at a strict condition with 1610 5 pfu (300-fold LD 50 ) of DENV-2 (NGC-N). After 21 days observation, mice showed ruffled fur, mild paralysis and lost approximate 20% of their initial body weight at day 7 after infection (P,0.01), and then they all died within 7-18 days of infection ( Figures 2D and 2E ). In the prophylaxis experiments, antibodies (100 mg per mouse, intraperitoneally) were administered 1 day before infection and at day 0, 1, 3, 5 and 7 after infection. The DB32-6 prophylactically treated group showed 100% protection ( Figure 2D left) . Even in the postexposure therapeutic experiments, the DB32-6 treated mice had a survival rate of 50% (Figure 2E left) . The mAb DB32-6 had excellent neutralizing activity against different DENV-2 strains (16681 and NGC-N) in two mouse models.