Based on previous epitope mapping results, several epitopes have been shown to elicit strong neutralizing antibodies against individual flaviviruses that situated in E-DIII [14, 50] . Investigation of neutralizing epitopes on the E proteins may provide the framework for a detailed understanding of both specific mechanisms of the viral infection as well as the identification of the specific DENV domain that attaches to a cellular receptor. Phage display is useful in the identification of B-cell epitopes, including linear [32, 51] and conformational epitopes [29, 45] . However, these epitopes need to further elucidation using other methods. Combining different strategies provided a fast and reliable evidence for identifying epitopes (Figures 3 and 4) . To date, few mAbs possess better neutralizing activity than 3H5, which has been shown to bind to residues K305, E383 and P384 at the lateral ridge of E-DIII [17, 20] . DB32-6 had higher neutralizing activity than 3H5. Neutralizing epitope of DB32-6 was mapped on K310 residue in A-strand of E-DIII (Figure 4 ). Neutralizing epitope of another mAb DB25-2 was mapped on E311 residue in A-strand of E-DIII, too ( Figure 4) . These serotype-specific neutralizing epitopes located in the A-strand of E-DIII induced stronger neutralizing activity than those located on the lateral ridge of E-DIII. We aligned different DENV-2 genotypes and found that the K310 and E311 were frequently observed in DENV-2 ( Figure S5 ). The K310 may be important to DENV-2. Thus by binding DB32-6 to K310, it lead to dramatic neutralized DENV-2. To determine whether DB32-6 can neutralize diverse genotypes of DENV-2 is a critical step in evaluating the potential of therapeutic development in the future.