Potential for developing a SARS-CoV receptor-binding domain (RBD) recombinant protein as a heterologous human vaccine against coronavirus infectious disease (COVID)-19

Hum Vaccin Immunother. 2020 Jun 2;16(6):1239-1242. doi: 10.1080/21645515.2020.1740560. Epub 2020 Apr 16.


A SARS-CoV receptor-binding domain (RBD) recombinant protein was developed and manufactured under current good manufacturing practices in 2016. The protein, known as RBD219-N1 when formulated on Alhydrogel®, induced high-level neutralizing antibodies and protective immunity with minimal immunopathology in mice after a homologous virus challenge with SARS-CoV (MA15 strain). We examined published evidence in support of whether the SARS-CoV RBD219-N1 could be repurposed as a heterologous vaccine against Coronavirus Infectious Disease (COVID)-19. Our findings include evidence that convalescent serum from SARS-CoV patients can neutralize SARS-CoV-2. Additionally, a review of published studies using monoclonal antibodies (mAbs) raised against SARS-CoV RBD and that neutralizes the SARS-CoV virus in vitro finds that some of these mAbs bind to the receptor-binding motif (RBM) within the RBD, while others bind to domains outside this region within RBD. This information is relevant and supports the possibility of developing a heterologous SARS-CoV RBD vaccine against COVID-19, especially due to the finding that the overall high amino acid similarity (82%) between SARS-CoV and SARS-CoV-2 spike and RBD domains is not reflected in RBM amino acid similarity (59%). However, the high sequence similarity (94%) in the region outside of RBM offers the potential of conserved neutralizing epitopes between both viruses.

Keywords: COVID-19; Heterologous vaccine; SARS; SARS-CoV-2; coronavirus; receptor-binding domain; subunit vaccine.

Publication types

  • Review

MeSH terms

  • Betacoronavirus*
  • COVID-19
  • COVID-19 Vaccines
  • Coronavirus Infections / immunology
  • Coronavirus Infections / prevention & control*
  • Humans
  • Pandemics / prevention & control*
  • Pneumonia, Viral / prevention & control*
  • Protein Domains
  • Protein Subunits
  • Recombinant Proteins / immunology*
  • SARS-CoV-2
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / immunology
  • Viral Vaccines / immunology*


  • COVID-19 Vaccines
  • Protein Subunits
  • Recombinant Proteins
  • Viral Envelope Proteins
  • Viral Vaccines