Human antibody responses after dengue virus infection are highly cross reactive to Zika virus
Significance In this study, we address the issue of cross reactivity between dengue virus (DENV) and Zika virus (ZIKV) by testing sera and plasmablast derived monoclonal antibodies from dengue patients against ZIKV. We show that both acute and convalescent dengue sera potently bind and neutralize ZIKV and that this cross reactivity is also evident at the monoclonal level. We also demonstrate in vitro antibody dependent enhancement of ZIKV infection in the presence of dengue induced antibodies. Our findings strongly suggest that preexisting dengue antibodies may modulate immune responses to ZIKV infection. These data are timely and highly relevant from a public health standpoint given that a majority of regions currently experiencing Zika virus epidemics are endemic for dengue. Zika virus (ZIKV) is an emerging mosquito borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV) resulting in immunological cross reactivity. Improving our current understanding of the extent and characteristics of this immunological cross reactivity is important, as ZIKV is presently circulating in areas that are highly endemic for dengue. To assess the magnitude and functional quality of cross reactive immune responses between these closely related viruses, we tested acute and convalescent sera from nine Thai patients with PCR confirmed DENV infection against ZIKV. All of the sera tested were cross reactive with ZIKV, both in binding and in neutralization. To deconstruct the observed serum cross reactivity in depth, we also characterized a panel of DENV specific plasmablast derived monoclonal antibodies (mAbs) for activity against ZIKV. Nearly half of the 47 DENV reactive mAbs studied bound to both whole ZIKV virion and ZIKV lysate, of which a subset also neutralized ZIKV. In addition, both sera and mAbs from the dengue infected patients enhanced ZIKV infection of Fc gamma receptor (FcgR) bearing cells in vitro. Taken together, these findings suggest that preexisting immunity to DENV may impact protective immune responses against ZIKV. In addition, the extensive cross reactivity may have implications for ZIKV virulence and disease severity in DENV experienced populations.
Proceedings of the National Academy of Sciences