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

J Immunol Methods. 2021 Jan:488:112900. doi: 10.1016/j.jim.2020.112900. Epub 2020 Oct 16.

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.

Keywords: Antibody-dependent cell-mediated cytotoxicity (ADCC); Chimeric ZIKV prM-E protein; Zika virus (ZIKV).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Antibodies, Viral / immunology*
  • Antibody-Dependent Cell Cytotoxicity*
  • Case-Control Studies
  • Cell Line
  • 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 / genetics
  • Zika Virus / immunology*
  • Zika Virus / pathogenicity
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / virology

Substances

  • Antibodies, Viral
  • Viral Envelope Proteins
  • prM protein, Flavivirus