Non-structural protein 1-specific antibodies directed against Zika virus in humans mediate antibody-dependent cellular cytotoxicity

Luis A. Sanchez Vargas, Awadalkareem Adam, Mary Masterson, Madison Smith, Zoe L. Lyski, Kimberly A. Dowd, Theodore C. Pierson, William B. Messer, Jeffrey R. Currier, Anuja Mathew

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

There is growing interest in understanding antibody (Ab) function beyond neutralization. The non-structural protein 1 (NS1) of Zika virus (ZIKV) is an attractive candidate for an effective vaccine as Abs against NS1, unlike the envelope or premembrane, do not carry the risk of mediating antibody-dependent enhancement. Our aim was to evaluate whether ZIKV NS1 Abs elicited following natural infection in humans can mediate antibody-dependent cellular cytotoxicity (ADCC). We evaluated the isotype specificity of ZIKV-specific Abs in immune sera and supernatants from stimulated immune PBMC and found that Abs against ZIKV NS1 and virus-like particles were predominantly of the IgG1 isotype. Using a recently developed FluoroSpot assay, we found robust frequencies of NS1-specific Ab-secreting cells in PBMC of individuals who were naturally infected with ZIKV. We developed assays to measure both natural killer cell activation by flow cytometry and target cell lysis of ZIKV NS1-expressing cells using an image cytometry assay in the presence of ZIKV NS1 Abs. Our data indicate efficient opsonization of ZIKV NS1-expressing CEM-NKR cell lines using ZIKV-immune but not ZIKV-naïve sera, a prerequisite of ADCC. Furthermore, sera from immune donors were able to induce both NK cell degranulation and lysis of ZIKV NS1 CEM-NKR cells in vitro. Our data suggest that ADCC is a possible mechanism for ZIKV NS1 Abs to eliminate virally infected target cells.

Original languageEnglish (US)
Pages (from-to)386-397
Number of pages12
JournalImmunology
Volume164
Issue number2
DOIs
StatePublished - Oct 2021

Keywords

  • B cell
  • FluoroSpot
  • Zika virus
  • antibody-dependent cellular cytotoxicity
  • humans
  • immunity
  • non-structural protein 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Non-structural protein 1-specific antibodies directed against Zika virus in humans mediate antibody-dependent cellular cytotoxicity'. Together they form a unique fingerprint.

Cite this