We established a suckling mice model to determine the protective activity of mDB32-6 and hDB32-6. To evaluate Humanized mAb against Dengue Virus www.plosntds.org therapeutic effect of mAbs, we administered 5 mg of mAb at day one after 1610 4 pfu (25-fold LD 50 ) of DENV-2 (16681) infection. Through 21 days of observation, groups treated with mDB32-6, hDB32-6-48 and 3H5 mAbs were found to have survival rates of 96%, 94% and 56%, respectively ( Figure 6 ). However, none of the mice in control antibody normal human IgG (NHIgG)-treated group survived (Figures 6) . These results demonstrate that both mDB32-6 and hDB32-6 have excellent neutralizing activity against DENV-2. mAb hDB32-6 variant eliminate ADE phenomenon When developing the antibody-based therapy, ADE phenomenon is a major cause for concern in dengue pathogenesis because it might enhance DENV infection. Modification of Fc structure in an antibody can prevent Fcc receptors binding and lead to eliminate ADE [38, 39, 48] . We generated a variant of humanized DB32-6 (hDB32-6 variant) to prevent Fcc receptors binding while maintaining DENV neutralizing capability without enhancing infection (Figure 7) . The hDB32-6 variant retained the same neutralizing activity as unmodified mAb mDB32-6 at high concentrations (100 mg/ml and 10 mg/ml) but was completely devoid of enhancing activity at low concentrations (1 mg/ml and 0.1 mg/ml) (Figure 7) . The hDB32-6 variant eliminated the ADE phenomenon and holds great potential for being developed into therapeutic antibodies for the prevention and treatment of DENV-2 infection.