SARS-CoV-2 tetrameric RBD protein blocks viral infection and induces potent neutralizing antibody response

Front Immunol. 2022 Oct 31:13:960094. doi: 10.3389/fimmu.2022.960094. eCollection 2022.

Abstract

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy and calls for the development of safe treatments and effective vaccines. The receptor-binding domain in the spike protein (SRBD) of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that dimeric SRBD-Fc and tetrameric 2xSRBD-Fc fusion proteins bind ACE2 with different affinity and block SARS-CoV-2 pseudoviral infection. Immunization of mice with SRBD-Fc fusion proteins elicited high titer of RBD-specific antibodies with robust neutralizing activity against pseudoviral infections. As such, our study indicates that the polymeric SRBD-Fc fusion protein can serve as a treatment agent as well as a vaccine for fighting COVID-19.

Keywords: 2xS-RBD-mFc; SARS-CoV-2; Vaccine; hACE2; viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antibodies, Neutralizing*
  • COVID-19 Vaccines
  • COVID-19*
  • Humans
  • Membrane Glycoproteins / metabolism
  • Mice
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins

Substances

  • Antibodies, Neutralizing
  • Angiotensin-Converting Enzyme 2
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • COVID-19 Vaccines
  • Membrane Glycoproteins
  • spike protein, SARS-CoV-2