DIFFERENTIAL CROSS-NEUTRALIZATION OF DENGUE IMMUNE SERA AGAINST ZIKA VIRUS

Abstract

Intro: Zika virus (ZIKV) is transmitted to humans primarily via the bites of infected female Aedes aegypti and Aedes albopictus. The mosquitoes are also the vector for the transmission of dengue viruses. Malaysia is a dengue hyperendemic country. To date, there has been no ZIKV-associated outbreak reported, could immunity from dengue virus (DENV) infection cross-neutralizes ZIKV, remains unknown. Here, we investigate the neutralization capacity of dengue immune serum against the different ZIKV strains. Methods: Healthy blood donor serum samples were retrieved and screened for the presence of dengue and Zika antibodies using Dengue virus-specific IgM and IgG ELISA and anti-ZIKV IgM and IgG ELISA kits. Selected sera samples were then evaluated for their neutralizing capacity against the ZIKV strains, ZIKV P6-740 and ZIKV PRVABC59, using the Foci Reduction Neutralization Test (FRNT). Results were analyzed according to the neutralizing antibody titers with 50% reduction of foci numbers (FRNT50) and 90% reduction of foci numbers (FRNT90) as the cut-off points. Findings: Based on the ELISA results, 118 of 215 samples were positive for dengue IgG but negative for dengue IgM and Zika antibodies. A subset of 43 (DENV IgM-/IgG+ with ZIKV IgM-/IgG-) sera samples was selected for subsequent neutralization assay. Neutralization results showed that 40 samples (93.0%) and 19 samples (44.2%) were positive (FRNT50 ≥20 and FRNT90 ≥20) for ZIKV neutralizing antibodies, respectively. In addition, 22 samples (55.0%) showed differential neutralization (FRNT50) with ≥ 4-fold differences against two ZIKV strains. Conclusion: Results from the study showed that dengue immune sera could cross-neutralize ZIKV efficiently. Neutralization efficient across both ZIKV strains. In addition, we also demonstrated that dengue immune sera could induce differential neutralization capacities against different ZIKV strains. These findings have implications in our understanding of the importance of serum cross reactivity in flavivirus infection.