The 17 immunopositive phage clones that were highly reactive with DB32-6 were amplified and phage DNA was isolated for DNA sequencing. All of the phage clones displayed 12 amino acid (aa) residues ( Figure 3D left) . Phage-displayed peptide sequences selected by DB32-6 had the consensus motifs of histidine (H)-lysine (K)-glutamic acid (E)-tryptophan (W)/tyrosine (Y)-histidine (H) (Figure 3D left) . Similarly, 17 immunopositive phage clones selected by DB32-6 using phage library displayed 7 amino acid residues, which contained the consensus motif H-K-E-W/Y-H ( Figure 3D left) . Interestingly, all phage-displayed peptides selected by DB32-6 and DB25-2 contained lysine (K) and glutamic acid (E), respectively ( Figure 3D ). To further confirm the neutralizing epitopes, we developed various E protein epitope-specific variants VLPs and screened lossof-binding VLP mutants for identification of critical recognition residues. Using this strategy, we found that DB32-6 lost its VLP binding activity when the residue K310 in the A-strand of E-DIII was changed to alanine (K310A) or glutamine (K310Q) (Figure 4A  left) . Similarly, DB25-2 lost its VLP binding activity when E311 was changed to arginine (E311R) in the A-strand of E-DIII ( Figure 4A right). Both the critical recognition residues K310 and E311 were located in the A-strand of E-DIII (Figures 4B and 4C) . We found that mAb 3H5 recognized residues K305, E383 and P384 ( Figure  S4 ), as previously reported [17, 20] . Notably, even the adjacent residues (K310 and E311) induced antibodies with different levels of neutralizing activity. By comparing the amino acid sequences of E proteins from representing genotypes of DENV-2 (Table S1), we found residues K310 and E311 in E-DIII of the different genotypes (Southeast Asian, West African and American) ( Figure S5 ). Our data further showed epitopes in the A-strand of E-DIII were important for inducing neutralizing antibodies.