Characterization of serological response to dengue and Zika viruses in pregnant women during the Zika outbreak in Brazil

Abstract

Abstract The outbreak of Zika virus (ZIKV) and associated congenital Zika syndrome in dengue virus (DENV)-endemic regions raised questions about the effects of ZIKV infection on DENV immunity and disease outcome and vice versa, which highlighted the need of serological tests that can discriminate between DENV and ZIKV infections. Previously we developed combined DENV and ZIKV non-structural protein 1 (NS1) enzyme-linked immunosorbent assays (ELISAs) to overcome the cross-reactivity of traditional envelope protein-based serological tests (Tsai et al. Clin Infect Dis 2017;65:1829). In this study, we used this assay to screen 120 serum samples collected from asymptomatic parturient women during the ZIKV outbreak in Salvador, Brazil and identified four serostatus groups. We further characterized antibody responses in 8 participants including 2 primary DENV (pDENV), 2 secondary DENV (sDENV), 1 primary ZIKV (pZIKV), and 3 ZIKV with previous DENV (ZIKVwprDENV) infections. Using depletion experiments with inactivated ZIKV and urea tests, we determined the IgG avidity to DENV. Using depletion experiments with inactivated DENV and endpoint ELISA titers, we determined ZIKV type-specific and cross-reactive antibody and found pZIKV had higher proportion of ZIKV type-specific antibody (82%) than ZIKVwprDENV (10-16%). These results were supported by microneutralization tests. Our findings suggest that combined DENV and ZIKV NS1 IgG ELISAs plus depletion experiments can delineate past and present DENV and ZIKV infections and are a potential tool to further our understanding of pathogenesis and epidemiology of DENV and ZIKV in endemic regions. Research supported by R01 AI11076901, R21AI135292-01A1 from NIAID, and P30GM114737 from NIGMS, NIH.