Zika Virus Antibody Titers Three Years after Confirmed Infection

Abstract

Background: In 2015-2016, a large Zika virus (ZIKV) outbreak occurred in the Americas. Although the exact ZIKV antibody kinetics after infection are unknown, recent evidence indicates the rapid waning of ZIKV antibodies in humans. Therefore, we aimed to determine the levels of ZIKV antibodies more than three years after a ZIKV infection.

Methods: We performed ZIKV virus neutralization tests (VNT) and a commercial ZIKV non-structural protein 1 (NS1) IgG ELISA in a cohort of 49 participants from Suriname who had a polymerase-chain-reaction-confirmed ZIKV infection more than three years ago. Furthermore, we determined the presence of antibodies against multiple dengue virus (DENV) antigens.

Results: The ZIKV seroprevalence in this cohort, assessed with ZIKV VNT and ZIKV NS1 IgG ELISA, was 59.2% and 63.3%, respectively. There was, however, no correlation between these two tests. Furthermore, we did not find evidence of a potential negative influence of DENV immunity on ZIKV antibody titers.

Conclusions: ZIKV seroprevalence, assessed with two commonly used serological tests, was lower than expected in this cohort of participants who had a confirmed previous ZIKV infection. This can have implications for future ZIKV seroprevalence studies and possibly for the duration of immunological protection after a ZIKV infection.

Keywords: Zika virus; cross-reactivity; dengue virus; serology; waning immunity.

Figure A1

Correlations between ZIKV NS1 IgG titers determined with a protein microarray (PMA) compared to titers from other serological assays. A: Correlation between ZIKV NS1 PMA IgG titers and titers from the ZIKV VNT. The dotted line indicates the cut-off value for a positive ZIKV VNT test result. B: Correlation between ZIKV NS1 PMA IgG titers and titers from the DENV-2 VNT. The dotted line indicates the cut-off value for a positive DENV-2 VNT test result. C: Correlation between ZIKV NS1 PMA IgG titers and ratios from the ZIKV NS1 IgG ELISA. The dotted line indicates the cut-off value for a positive ZIKV NS1 IgG ELISA test result.

Figure 1

Results from serological assays for ZIKV and DENV antibodies. A: Percentage of positive and negative tested sera with ZIKV VNT and ZIKV NS1 IgG ELISA. B: Correlation between ZIKV NS1 IgG ELISA ratios and titers from the ZIKV VNT. The dotted lines indicate cut-off values for a positive test result. C: ZIKV- and DENV-2 VNT titers from all participants. Lines represent median ± IQR. The dotted line indicates the cut-off value for a positive test result. Statistical differences were tested with the Mann–Whitney test. D: Correlation between DENV-2 VNT titers and ZIKV VNT titers. The dotted lines indicate cut-off values for a positive test result. E: Correlation between ZIKV NS1 IgG ELISA ratios and DENV-2 VNT titers. The dotted lines indicate cut-off values for a positive test result. * P < 0.05.

Figure 2

Heatmap of results from the different serological assays used in this study. A: IgG antibody titers for DENV1–4 Equad and DENV1–4 and ZIKV NS1 antigens determined with a protein microarray. Corresponding ZIKV and DENV-2 VNT titers and ZIKV NS1 IgG ELISA ratios from all participants are shown on the right. Antibody patterns are ranked from highest to lowest ZIKV VNT titer. B: Protein microarray IgG antibody titer patterns for DENV1–4 Equad and DENV1–4 and ZIKV NS1, ZIKV and DENV-2 VNT titers and ZIKV NS1 IgG ELISA ratios from all participants, ranked from highest to lowest ZIKV NS1 ELISA ratio. Numbers on the left Y-axis are the study numbers of the participants in this study. PA; protein microarray, Equad; envelope proteins containing four amino acid mutations in the highly conserved fusion loop domain to reduce flavivirus cross-reactivity, VNT; virus neutralization test.