A surrogate cell-based SARS-CoV-2 spike blocking assay

Eur J Immunol. 2021 Nov;51(11):2665-2676. doi: 10.1002/eji.202149302. Epub 2021 Sep 28.

Abstract

To monitor infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and successful vaccination against coronavirus disease 2019 (COVID-19), the kinetics of neutralizing or blocking anti-SARS-CoV-2 antibody titers need to be assessed. Here, we report the development of a quick and inexpensive surrogate SARS-CoV-2 blocking assay (SUBA) using immobilized recombinant human angiotensin-converting enzyme 2 (hACE2) and human cells expressing the native form of surface SARS-CoV-2 spike protein. Spike protein-expressing cells bound to hACE2 in the absence or presence of blocking antibodies were quantified by measuring the optical density of cell-associated crystal violet in a spectrophotometer. The advantages are that SUBA is a fast and inexpensive assay, which does not require biosafety level 2- or 3-approved laboratories. Most importantly, SUBA detects blocking antibodies against the native trimeric cell-bound SARS-CoV-2 spike protein and can be rapidly adjusted to quickly pre-screen already approved therapeutic antibodies or sera from vaccinated individuals for their ACE2 blocking activities against any emerging SARS-CoV-2 variants.

Keywords: COVID-19; SARS-CoV-2; Spike protein; Surrogate blocking assay; hACE2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Blocking / blood*
  • Antibodies, Blocking / immunology
  • Antibodies, Neutralizing / blood*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / analysis*
  • COVID-19 / diagnosis*
  • COVID-19 / immunology
  • COVID-19 Serological Testing / methods*
  • Flow Cytometry / methods*
  • Humans
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / immunology

Substances

  • Antibodies, Blocking
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2