Most current dengue vaccines consist of both prM and E proteins [12, 13, 35] ; studies performed with tick-borne encephalitis virus indicate that proper folding of E requires the chaperone function of prM [36] . However, as demonstrated in this study and recent reports, prM-specific antibodies are able to restore and enhance the infectivity of imDENV and partially mature DENV [9, 11, 12] ; it may be worthwhile to consider alternative vaccine approaches that minimize anti-prM responses during vaccine design [9] . The findings from our study also suggest that any partial denaturation or unfolding of an E protein vaccine preparation may result in the exposure of a cryptic P9-like epitope, which has the potential to induce D29-like antibodies with threatening ADE capability.