Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods

Cell Mol Immunol. 2021 Apr;18(4):936-944. doi: 10.1038/s41423-020-00573-9. Epub 2020 Nov 2.

Abstract

Neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells via surface-expressed angiotensin-converting enzyme 2 (ACE2). We used a surrogate virus neutralization test (sVNT) and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus (VSV) vector-based neutralization assay (pVNT) to assess the degree to which serum antibodies from coronavirus disease 2019 (COVID-19) convalescent patients interfere with the binding of SARS-CoV-2 S to ACE2. Both tests revealed neutralizing anti-SARS-CoV-2 S antibodies in the sera of ~90% of mildly and 100% of severely affected COVID-19 convalescent patients. Importantly, sVNT and pVNT results correlated strongly with each other and to the levels of anti-SARS-CoV-2 S1 IgG and IgA antibodies. Moreover, levels of neutralizing antibodies correlated with the duration and severity of clinical symptoms but not with patient age. Compared to pVNT, sVNT is less sophisticated and does not require any biosafety labs. Since this assay is also much faster and cheaper, sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy.

Keywords: COVID-19; ELISA; Neutralizing antibody; SARS-CoV-2; Serum.

MeSH terms

  • Adult
  • Aged
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood*
  • COVID-19 / blood
  • COVID-19 / immunology*
  • Cell Line
  • Convalescence
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Neutralization Tests / methods
  • Spike Glycoprotein, Coronavirus / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin A
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2