Prior dengue immunity enhances Zika virus infection of the maternal-fetal interface in rhesus macaques

Crooks, C. M.; Weiler, A. M.; Rybarczyk, S. L.; Bliss, M. I.; Jaeger, A. S.; Murphy, M. E.; Simmons, H. A.; Mejia, A.; Fritsch, M. K.; Hayes, J. M.; Eickhoff, J. C.; Mitzey, A. M.; Razo, E.; Braun, K. M.; Brown, E. A.; Yamamoto, K.; Shepherd, P. M.; Possell, A.; Weaver, K.; Antony, K. M.; Morgan, T. K.; Newman, C. M.; Dudley, D. M.; Schultz-Darken, N.; Peterson, E.; Katzelnick, L. C.; Balmaseda, A.; Harris, E.; O’Connor, D. H.; Mohr, E. L.; Golos, T. G.; Friedrich, T. C.; Aliota, M. T.

Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that prior DENV-2 exposure enhanced ZIKV infection of maternal-fetal interface tissues in macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.