To gain a deeper understanding of the early immune response against DENV, we have isolated and characterised a highly crossreactive antibody fragment -D29, from a non-immune human Fab-phage library that shows near germline sequence. Upon conversion into full-length IgG, D29 showed cross-reactivity against all four serotypes of DENV and could be competed with the prM-specific mouse antibody 2H2. Intriguingly, D29 Fab-IgG was found to recognize both E and prM during Western blot analysis in a conformational dependant manner. Cross-reactivity between E and prM has been observed in antibodies isolated from mice as well as human patients [10, 11, 21] . However, the binding epitopes of these antibodies remain unknown and the observation is usually explained by general cross-reactivity of anti-prM antibodies.