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

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-depen...

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Bibliographic Details
Published in:Journal of immunological methods 2021-01, Vol.488, p.112900-112900, Article 112900
Main Authors: Chen, Xuemin, Anderson, Larry J., Rostad, Christina A., Ding, Lingmei, Lai, Lilin, Mulligan, Mark, Rouphael, Nadine, Natrajan, Muktha S., McCracken, Courtney, Anderson, Evan J.
Format: Article
Language:English
Subjects:
Antibodies, Viral - immunology
Antibody-Dependent Cell Cytotoxicity
Antibody-dependent cell-mediated cytotoxicity (ADCC)
Case-Control Studies
Cell Line
Chimeric ZIKV prM-E protein
Cytotoxicity Tests, Immunologic
Host-Pathogen Interactions
Humans
Predictive Value of Tests
Reproducibility of Results
Transfection
Viral Envelope Proteins - genetics
Viral Envelope Proteins - immunology
Zika virus (ZIKV)
Zika Virus - genetics
Zika Virus - immunology
Zika Virus - pathogenicity
Zika Virus Infection - immunology
Zika Virus Infection - virology
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Summary: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.
ISSN:0022-1759
1872-7905
DOI:10.1016/j.jim.2020.112900