Enhanced elicitation of potent neutralizing antibodies by the SARS-CoV-2 spike receptor binding domain Fc fusion protein in mice

Vaccine. 2020 Oct 27;38(46):7205-7212. doi: 10.1016/j.vaccine.2020.09.058. Epub 2020 Sep 22.

Abstract

The development of an effective vaccine against SARS-CoV-2 is urgently needed. We generated SARS-CoV-2 RBD-Fc fusion protein and evaluated its potency to elicit neutralizing antibody response in mice. RBD-Fc elicited a higher neutralizing antibodies titer than RBD as evaluated by a pseudovirus neutralization assay and a live virus based microneutralization assay. Furthermore, RBD-Fc immunized sera better inhibited cell-cell fusion, as evaluated by a quantitative cell-cell fusion assay. The cell-cell fusion assay results correlated well with the virus neutralization potency and could be used for high-throughput screening of large panels of anti-SARS-CoV-2 antibodies and vaccines without the requirement of live virus infection in BSL3 containment. Moreover, the anti-RBD sera did not enhance the pseudotyped SARS-CoV-2 infection of K562 cells. These results demonstrate that Fc fusion can significantly improve the humoral immune response to recombinant RBD immunogen, and suggest that RBD-Fc could serve as a useful component of effective vaccines against SARS-CoV-2.

Keywords: Cell–cell fusion assay; Receptor-binding domain (RBD); SARS-CoV-2; Subunit vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • Betacoronavirus / immunology
  • COVID-19
  • COVID-19 Vaccines
  • Cell Fusion
  • Cell Line
  • Coronavirus Infections / immunology
  • Coronavirus Infections / prevention & control*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HEK293 Cells
  • High-Throughput Screening Assays / methods
  • Humans
  • Immunity, Humoral / immunology
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Pandemics / prevention & control*
  • Peptidyl-Dipeptidase A / genetics
  • Pneumonia, Viral / prevention & control*
  • Protein Domains / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology*
  • Vaccines, Subunit / immunology
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Subunit
  • Viral Vaccines
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2