mAbs of DENV have served as powerful research tools for antiviral development and pathological investigations. Here, we newly generated and characterized 17 mAbs with high reactivity against E protein of DENV-2. Several mAbs had potent neutralizing activity. The neutralizing epitopes were identified using a combination of strategies, including phage display, computational structure analysis [49] , and high-throughput epitope mapping of VLPs. From these results, the A-strand of E-DIII was found to be important in neutralizing DENV-2 than the Humanized mAb against Dengue Virus www.plosntds.org lateral ridge of E-DIII. mAb DB32-6 which had the strongest neutralizing activity against various strains of DENV-2 was humanized and modified to abrogate the ADE phenomenon. The mAb DB32-6 was demonstrated to increase the survival rate in two mouse models even after DENV-2 infection.