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

Zheng Liu1, Chenglu Yang1, Haokun Zhang1

  • 1Laboratory of Epigenetics and Translational Medicine, School of Life Sciences, Henan University, Kaifeng, Henan, China.

Frontiers in Immunology
|November 17, 2022
PubMed

Insights

Polymeric SARS-CoV-2 spike receptor-binding domain (SRBD)-Fc fusion proteins effectively neutralize the virus. These fusion proteins show potential as both a COVID-19 vaccine and a therapeutic treatment agent.

Area of Science:

  • Virology
  • Immunology
  • Biotechnology

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, necessitates novel vaccines and treatments.
  • The SARS-CoV-2 spike protein's receptor-binding domain (SRBD) is crucial for viral entry via ACE2 binding and contains key neutralizing epitopes.

Purpose of the Study:

  • To investigate the potential of dimeric and tetrameric SRBD-Fc fusion proteins as COVID-19 therapeutics and vaccines.
  • To evaluate the binding affinity of SRBD-Fc fusion proteins to ACE2 and their efficacy in blocking viral infection.

Main Methods:

  • Construction and characterization of dimeric SRBD-Fc and tetrameric 2xSRBD-Fc fusion proteins.
  • Assessment of fusion protein binding to ACE2 and inhibition of SARS-CoV-2 pseudoviral infection.
  • Immunization of mice with SRBD-Fc fusion proteins to evaluate antibody response and neutralizing activity.

Main Results:

  • Dimeric and tetrameric SRBD-Fc fusion proteins exhibited distinct binding affinities to ACE2.
  • Fusion proteins demonstrated significant blockade of SARS-CoV-2 pseudoviral infection.
  • Immunization induced high titers of SRBD-specific antibodies with potent neutralizing capabilities against pseudoviruses.

Conclusions:

  • Polymeric SRBD-Fc fusion proteins are effective in neutralizing SARS-CoV-2.
  • These fusion proteins represent a promising strategy for both COVID-19 vaccine development and therapeutic intervention.