Our current understanding of how antibodies interact with DENV and other flaviviruses is primarily based on studies utilizing mouse monoclonal antibodies (MAbs) (Reviewed in [10] ). The DENV envelope (E) protein is the principle target of neutralizing antibodies. Antibody neutralization occurs by blocking critical functions of the E protein, including attachment to host cells and low pH-dependent fusion of the viral and host cell membranes [11] . The crystal structures of the E protein of several flaviviruses have been solved [12] [13] [14] [15] . Individual subunits of E protein consist of three beta-barrel domains designated domains I (EDI), II (EDII) and III (EDIII), with the native protein forming a head-totail homodimer. Mouse MAbs that bind to all three domains of DENV E have been generated and characterized [16] [17] [18] [19] [20] [21] [22] [23] . Although neutralizing mouse MAbs have been mapped to all three domains of E, the most strongly neutralizing MAbs recognize epitopes on the lateral ridge and A strand of EDIII [24] .