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Antibody responses to Zika virus infections in flavivirus-endemic environments.

Research paper by Sarah L SL Keasey, Christine L CL Pugh, Stig M R SM Jensen, Jessica L JL Smith, Robert D RD Hontz, Anna P AP Durbin, Dawn M DM Dudley, David H DH O'Connor, Robert G RG Ulrich

Indexed on: 24 Feb '17Published on: 24 Feb '17Published in: Clinical and vaccine immunology : CVI



Abstract

Zika virus (ZIKV) infections occur in areas where dengue (DENV), West Nile (WNV), yellow fever (YFV), and other viruses of the genus Flavivirus co-circulate. The envelope protein (E) of these closely related flaviviruses induces specific long-term immunity, yet subsequent infections are associated with cross-reactive antibody responses that may enhance disease susceptibility and severity. To gain a better understanding of ZIKV infections against a background of similar viral diseases, we examined serological immune responses to ZIKV, WNV, DENV and YFV infections of humans and non-human primates (NHP). Using printed microarrays, we detected very specific antibody responses to primary infections with probes of recombinant E proteins from fifteen species and lineages of flaviviruses pathogenic to humans, while high cross-reactivity between ZIKV and DENV was observed with eleven printed native viruses. Notably, antibodies from human primary ZIKV or secondary DENV infections that occurred in flavivirus-endemic areas broadly recognized E proteins from many flaviviruses, especially DENV, indicating a strong influence of infection history on immune responses. A predictive algorithm was used to tentatively identify previous encounters with specific flaviviruses based on serum antibody interactions with the multi-species panel of E proteins. These results illustrate the potential impact of exposures to related viruses on the outcome of ZIKV infection, and offer considerations for development of vaccines and diagnostics.

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