SARS-CoV-2 specific antibody and neutralization assays reveal the wide range of the humoral immune response to virus

Commun Biol. 2021 Jan 29;4(1):129. doi: 10.1038/s42003-021-01649-6.

Abstract

Development of antibody protection during SARS-CoV-2 infection is a pressing question for public health and for vaccine development. We developed highly sensitive SARS-CoV-2-specific antibody and neutralization assays. SARS-CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects (n = 115) and were absent in the negative controls. Other isotype antibodies (IgA, IgG1-4) were also detected. SARS-CoV-2 neutralization was determined in COVID-19 and convalescent plasma at up to 10,000-fold dilution, using Spike protein pseudotyped lentiviruses, which were also blocked by neutralizing antibodies (NAbs). Hospitalized patients had up to 3000-fold higher antibody and neutralization titers compared to outpatients or convalescent plasma donors. Interestingly, some COVID-19 patients also possessed NAbs against SARS-CoV Spike protein pseudovirus. Together these results demonstrate the high specificity and sensitivity of our assays, which may impact understanding the quality or duration of the antibody response during COVID-19 and in determining the effectiveness of potential vaccines.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme 2 / chemistry
  • Angiotensin-Converting Enzyme 2 / immunology
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / chemistry*
  • COVID-19 / diagnosis*
  • COVID-19 / immunology
  • COVID-19 / virology
  • Convalescence
  • Coronavirus Nucleocapsid Proteins / chemistry*
  • Coronavirus Nucleocapsid Proteins / immunology
  • Coronavirus Nucleocapsid Proteins / metabolism
  • Enzyme-Linked Immunosorbent Assay / methods
  • Epitopes / chemistry
  • Epitopes / immunology
  • Epitopes / metabolism
  • Female
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Humans
  • Immune Sera / chemistry
  • Immunity, Humoral
  • Lentivirus / genetics
  • Lentivirus / immunology
  • Male
  • Middle Aged
  • Neutralization Tests
  • Phosphoproteins / chemistry
  • Phosphoproteins / immunology
  • Phosphoproteins / metabolism
  • Protein Binding
  • Receptors, Virus / chemistry
  • Receptors, Virus / immunology
  • Receptors, Virus / metabolism
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / pathogenicity
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Survival Analysis

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Coronavirus Nucleocapsid Proteins
  • Epitopes
  • Immune Sera
  • Phosphoproteins
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2