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Updated: Dec 24, 2025
Quantification of Antibody-dependent Enhancement of the Zika Virus in Primary Human Cells
Published on: January 18, 2019
Potency and breadth of human primary ZIKV immune sera shows that Zika viruses cluster antigenically as a single
Chad D Nix1,2, Jonathan Salberg3, Felicity J Coulter2
1Dept. of Infection Prevention and Control, Oregon Health and Science University, Portland, Oregon, United States of America.
Abstract:
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.
Insights
Human immune sera effectively neutralize diverse Zika virus (ZIKV) strains, even months after infection. Antigenic cartography confirms Zika virus is a single serotype, indicating broad cross-protection from prior infection.
Area of Science:
- Virology
- Immunology
- Public Health
Background:
- Zika virus (ZIKV) emerged as a significant global health concern, particularly in the Americas since 2014.
- Phylogenetic analysis reveals ZIKV comprises African, Asian, and American lineages, prompting questions about immune responses to diverse strains.
- Previous studies on ZIKV cross-neutralization were limited by small sample sizes and early convalescent sera.
Purpose of the Study:
- To evaluate the breadth and potency of human immune sera against antigenically diverse ZIKV isolates.
- To assess the variability in neutralization susceptibility across different ZIKV genetic variants.
- To determine the antigenic relatedness of ZIKV strains using antigenic cartography.
Main Methods:
- Virus neutralization assays were employed using primary ZIKV immune sera from adults infected 5 to 38 months prior.
- A panel of 11 ZIKV isolates from African, Asian, and American lineages was tested against twelve human immune sera.
- Antigenic cartography was utilized to analyze the antigenic distances between ZIKV isolates.
Main Results:
- All tested sera demonstrated neutralization capabilities against all ZIKV isolates, with FRNT50 titers ranging from 1:271 to 1:4271.
- Minimal differences were observed in neutralization potency across subjects and in the susceptibility of ZIKV isolates to neutralization.
- Antigenic cartography revealed a narrow antigenic distance (~4-fold range) among ZIKV isolates, supporting a single serotype classification.
Conclusions:
- Primary ZIKV immune sera exhibit broad and potent neutralizing activity against diverse ZIKV lineages.
- The findings suggest that ZIKV is antigenically highly conserved, consistent with a single serotype.
- This implies that immunity acquired from ZIKV infection likely provides cross-protection against various circulating strains.
