Potency and breadth of human primary ZIKV immune sera shows that Zika viruses cluster antigenically as a single serotype.

Zika virus (ZIKV) emerged as a global public health threat throughout the Americas since 2014. Phylogenetically, the virus is composed of three main lineages, an African, Asian, and American lineage. The recent emergence and spread of ZIKV has raised questions regarding the breadth and potency of human primary ZIKV immune sera against antigenically diverse ZIKV. Although ZIKV is thought to compose a single antigenic serotype, in-depth evaluation of the antigenic relatedness of ZIKV across genetic variants has been limited to a relatively small series of early convalescent human immune sera (4-12 weeks) against a limited number (3) of genetic variants. Using virus neutralization assays, we characterize the potency and breadth of twelve primary ZIKV immune sera from adults infected 5 to 38 months previously against a panel of 11 ZIKV isolates from the African, Asian and American lineages. We assess the variability of neutralization potency of immune sera from these subjects and the variability of susceptibility to neutralization for each virus isolate. Overall, we found all sera neutralized all viruses at FRNT50 ranging from 1:271 to 1:4271, a 15.8-fold range, with only small differences between subject geometric mean titers (GMT) against all viruses and small differences between each ZIKV isolate and sensitivity to neutralization by all sera: when pooled, African strains were 1.3-fold more sensitive to neutralization by subject immune sera compared to pooled American strains. Finally, we subjected our data to analysis using antigenic cartography, finding that ZIKV are highly antigenically similar, with only a ~4-fold range across all antigenic distances between viruses, consistent with a single serotype.