Antibodies to E-DI-II tend to be more cross-reactive and less potent in neutralization of dengue infection [39] . However, there are fewer antibody concentrations capable of recognizing E-DIII than there are that recognize E-DI-II in dengue patients [20, 39] . Wahala et al. studied the human immune sera of DENV infection and found the E-DIII binding antibodies to play a minor role in DENV neutralization, similar to West Nile virus-infected human [52, 53] . The mAbs that bind to E-DIII expresses potent neutralizing activity, but only a few of them exist in serum of the patients infected with DENV or WNV. Combining the information from both mice and human mAbs studies of DENV infection is critical to understanding the complex mechanism behind the humoral immunity following natural DENV infection. According to one previous study, the immunoglobulin populations recognizing residues K310, E311 and P364 in dengue fever patients were much larger in IgM than in IgG [20] . The strong neutralizing IgG made up a small proportion of the antibody in dengue patients. de Alwis et al. has conducted an in-depth analysis of the human mAbs derived from memory B-cells of patients infected with primary DENV infections [54] . After the epitope mapping of anti-DENV-2 human mAbs, the strong neutralizing mAb 10.16 was mapped to K305, K310 and E311 in the A-strand. Together, the finding above suggest that the highly protective epitopes K310 and E311 in mouse play a role in humans as well.