Development and optimization of a Zika virus antibody-dependent cell-mediated cytotoxicity (ADCC) assay

寨卡病毒抗体依赖性细胞介导细胞毒性 (ADCC) 检测的开发和优化

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作者:Xuemin Chen, Larry J Anderson, Christina A Rostad, Lingmei Ding, Lilin Lai, Mark Mulligan, Nadine Rouphael, Muktha S Natrajan, Courtney McCracken, Evan J Anderson

Abstract

Zika virus (ZIKV) has become a global public health issue due to its teratogenicity and ability to cause Guillain-Barré syndrome in adults. Although anti-ZIKV envelope protein neutralizing antibodies correlate with protection, the non-neutralizing function of ZIKV antibodies including antibody-dependent cell-mediated cytotoxicity (ADCC) is incompletely understood. To study the role of ADCC antibodies during ZIKV infections, we generated a stably transfected, dual-reporter target cell line with inducible expression of a chimeric ZIKV prM-E protein on the cell surface as the target cell for the assay. By using this assay, nine of ten serum samples from ZIKV-infected patients had >20% ADCC killing of target cells, whereas none of the 12 healthy control sera had >10% ADCC killing. We also observed a time-dependent ADCC response in 2 patients with Zika. This demonstrates that this assay can detect ZIKV ADCC with high sensitivity and specificity, which could be useful for measurement of ADCC responses to ZIKV infection or vaccination.

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