Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity

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Science  14 Apr 2017:
Vol. 356, Issue 6334, pp. 175-180
DOI: 10.1126/science.aal4365

One antibody for all and all antibodies for one

Antibodies against related flavi-viruses such as dengue (DENV) and West Nile (WNV) can cross-react with Zika virus (ZIKV) and could thereby increase disease severity. Bardina et al. tested whether DENV and WNV antibodies from humans, or even yellow fever vaccination, could enhance ZIKV infection. In a mouse model, low titers of DENV and WNV antibodies enhanced ZIKV viremia, especially in the spinal cord and testes, whereas high titers remained protective. Generally, WNV antibodies were less disease-enhancing than DENV antibodies, and, in macaques, yellow fever vaccination had very little effect.

Science, this issue p. 175


Zika virus (ZIKV) is spreading rapidly into regions around the world where other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), are endemic. Antibody-dependent enhancement 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 immunoglobulin G engagement of Fcγ receptors. Administration of DENV- or WNV-convalescent plasma into ZIKV-susceptible mice resulted in increased morbidity—including fever, viremia, and viral loads in spinal cord and testes—and increased mortality. Antibody-dependent enhancement 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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