Egg yolk immunoglobulin (IgY) targeting SARS-CoV-2 S1 as potential virus entry blocker

J Appl Microbiol. 2022 Mar;132(3):2421-2430. doi: 10.1111/jam.15340. Epub 2021 Nov 3.

Abstract

Aims: COVID-19 pandemic caused by SARS-CoV-2 has become a public health crisis worldwide. In this study, we aimed at demonstrating the neutralizing potential of the IgY produced after immunizing chicken with a recombinant SARS-CoV-2 spike protein S1 subunit.

Methods and results: E. coli BL21 carrying plasmid pET28a-S1 was induced with IPTG for the expression of SARS-CoV-2 S1 protein. The recombinant His-tagged S1 was purified and verified by SDS-PAGE, Western blot and biolayer interferometry (BLI) assay. Then S1 protein emulsified with Freund's adjuvant was used to immunize layer chickens. Specific IgY against S1 (S1-IgY) produced from egg yolks of these chickens exhibited a high titer (1:25,600) and a strong binding affinity to S1 (KD = 318 nmol L-1 ). The neutralizing ability of S1-IgY was quantified by a SARS-CoV-2 pseudotyped virus-based neutralization assay with an IC50 value of 0.99 mg ml-1 . In addition, S1-IgY exhibited a strong ability in blocking the binding of SARS-CoV-2 S1 to hACE2, and it could partially compete with hACE2 for the binding sites on S1 by BLI assays.

Conclusions: We demonstrated here that after immunization of chickens with our recombinant S1 protein, IgY neutralizing antibodies were generated against the SARS-CoV-2 spike protein S1 subunit; therefore, showing the potential use of IgY to block the entry of this virus.

Significance and impact of the study: IgY targeting S1 subunit of SARS-CoV-2 could be a promising candidate for pre- and post-exposure prophylaxis or treatment of COVID-19. Administration of IgY-based oral preparation, oral or nasal spray may have profound implications for blocking SARS-CoV-2.

Keywords: COVID-19; S1; SARS-CoV-2; antibody; egg yolk immunoglobulin Y (IgY); hACE2.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / pharmacology*
  • COVID-19
  • Chickens
  • Egg Yolk / immunology
  • Humans
  • Immunoglobulins / pharmacology*
  • Pandemics
  • SARS-CoV-2 / drug effects*
  • Spike Glycoprotein, Coronavirus / antagonists & inhibitors*
  • Virus Internalization / drug effects*

Substances

  • Antibodies, Neutralizing
  • IgY
  • Immunoglobulins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2