Antibody landscape against SARS-CoV-2 reveals significant differences between non-structural/accessory and structural proteins

Cell Rep. 2021 Jul 13;36(2):109391. doi: 10.1016/j.celrep.2021.109391. Epub 2021 Jun 26.

Abstract

The immunogenicity of the SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. In this study, we collect 2,360 COVID-19 sera and 601 control sera. We analyze these sera on a protein microarray with 20 proteins of SARS-CoV-2, building an antibody response landscape for immunoglobulin (Ig)G and IgM. Non-structural proteins and accessory proteins NSP1, NSP7, NSP8, RdRp, ORF3b, and ORF9b elicit prevalent IgG responses. The IgG patterns and dynamics of non-structural/accessory proteins are different from those of the S and N proteins. The IgG responses against these six proteins are associated with disease severity and clinical outcome, and they decline sharply about 20 days after symptom onset. In non-survivors, a sharp decrease of IgG antibodies against S1 and N proteins before death is observed. The global antibody responses to non-structural/accessory proteins revealed here may facilitate a deeper understanding of SARS-CoV-2 immunology.

Keywords: COVID-19; SARS-CoV-2; humoral immunity; immune response; non-structural/accessory proteins; proteome microarray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / immunology
  • Antibody Formation
  • COVID-19 / immunology*
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Male
  • Middle Aged
  • Protein Array Analysis
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology*
  • Viral Nonstructural Proteins / immunology*
  • Viral Regulatory and Accessory Proteins / immunology*

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Immunoglobulin M
  • Spike Glycoprotein, Coronavirus
  • Viral Nonstructural Proteins
  • Viral Regulatory and Accessory Proteins
  • spike protein, SARS-CoV-2