Cross-reactive dengue virus-derived monoclonal antibodies to Zika virus envelope protein: Panacea or Pandora’s box?

BACKGROUND: Dengue Virus (DENV) and Zika Virus (ZIKV) are closely related flaviviruses, circulating in overlapping geographical regions. The recent ZIKV epidemic has been linked to an explosion in reports of microcephaly and neurological defects. It is conceivable that our knowledge of DENV might potentiate the development of a ZIKV vaccine due to the close phylogenetic relationship between these flaviviruses and cross-reactive antibodies, principally to the envelope protein (E protein). Alternatively, cross-reactive antibodies that are generated following vaccination or infection, might become damaging during subsequent infections. MAIN BODY: The aims of this review are to collate and analyse data from a recent series of DENV-derived monoclonal antibody (mAb) panels from different research groups. These panels measured DENV-mAb activity against ZIKV in terms of antibody-dependent enhancement (ADE) and neutralisation. Methodology used across groups was compared and critiqued. Furthermore, the specific antibody targets on E protein were considered and their therapeutic potential evaluated. Shortcomings of hmAb panels suggest ADE may be over-estimated and neutralisation underestimated, as compared to clinical situations. It remains unknown whether preference of enhancement or neutralisation by antibodies to ZIKV E protein is dictated by quantitative aspects of antibody titre or epitope specific variation. Additionally, little is known about how duration between flavivirus reinfections affect secondary antibody response. CONCLUSION: This review concludes that our current knowledge of cross-reactive antibodies to E protein is inadequate to anticipate the outcome of deploying an E protein based vaccine to regions co-infected by DENV and ZIKV.