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Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity

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Science  30 Mar 2017:
eaal4365
DOI: 10.1126/science.aal4365

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Abstract

Zika virus (ZIKV) is spreading rapidly into regions around the world where other flaviviruses, such as dengue (DENV) and West Nile virus (WNV) are endemic. Antibody-dependent enhancement (ADE) has been implicated in more severe forms of flavivirus disease, but whether this also applies to ZIKV infection is unclear. Using convalescent plasma from DENV and WNV infected individuals, we found substantial enhancement of ZIKV infection in vitro that was mediated through IgG engagement of Fcγ receptors. Administration of DENV or WNV convalescent plasma into ZIKV-susceptible mice resulted in increased morbidity and mortality, including fever, viremia, and viral loads in spinal cord and testes. ADE may explain the severe disease manifestations associated with recent ZIKV outbreaks and highlights the need to exert great caution when designing flavivirus vaccines.

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