Our studies show that the serotype-specific mAbs targeting the A-strand of E-DIII could serve as a dramatic neutralization determinant. Through testing in different mouse models, we have successfully generated a mAb hDB32-6 variant with high therapeutic potential against diverse DENV-2 strains without inducing ADE. Such an antibody-based therapy may help control severe dengue in the future. Figure S4 Identification of mAb 3H5 neutralizing epitopes by VLP mutants. BHK-21 cells expressed various DENV-2 VLP mutants. After fixation and permeabilization, mAbs were incubated with the cells. Binding activity was assessed Figure 6 . mAbs, mDB32-6 and hDB32-6-48, protected against DENV-2-induced mice mortality. Two-day-old suckling mice (ICR strain) were injected intracranially (i.c.) with 1610 4 pfu of DENV-2 (16681). After 1 day of infection, 5 mg of mAb were passively injected into mice through an i.c. route. Log rank test was used to determine significant differences in survival rate, and the mAbs with neutralizing activity were compared to the control group treated with NHIgG, P,0.001. doi:10.1371/journal.pntd.0001636.g006 Figure 7 . Antibody-mediated enhancement of DENV-2 infection by mAbs. Serial dilutions of NMIgG, 4G2, mDB32-6 and hDB32-6 variant were incubated with DENV-2 (16681) at MOI of 1 at 4uC for 1 h before they were added to K562 cells. After 2 days infection, cells were fixed, permeabilized, and stained with mAb DB42-3, and the percentage of cells infected with DENV-2 was detected by flow cytometry. doi:10.1371/journal.pntd.0001636.g007