Expression and Immunogenicity of SARS-CoV-2 Virus-Like Particles based on Recombinant Truncated HEV-3 ORF2 Capsid Protein

J Microbiol Biotechnol. 2022 Oct 28;32(10):1335-1343. doi: 10.4014/jmb.2205.05023. Epub 2022 Sep 19.

Abstract

COVID-19 is an emerging disease that poses a severe threat to global public health. As such, there is an urgent demand for vaccines against SARS-CoV-2, the virus that causes COVID-19. Here, we describe a virus-like nanoparticle candidate vaccine against SARS-CoV-2 produced by an E. coli expression system. The fusion protein of a truncated ORF2-encoded protein of aa 439~608 (p170) from hepatitis E virus CCJD-517 and the receptor-binding domain of the spike protein from SARS-CoV-2 were expressed, purified and characterized. The antigenicity and immunogenicity of p170-RBD were evaluated in vitro and in Kunming mice. Our investigation revealed that p170-RBD self-assembled into approximately 24 nm virus-like particles, which could bind to serum from vaccinated people (p < 0.001) and receptors on cells. Immunization with p170-RBD induced the titer of IgG antibody vaccine increased from 14 days post-immunization and was significantly enhanced after a booster immunization at 28 dpi, ultimately reaching a peak level on 42 dpi with a titer of 4.97 log10. Pseudovirus neutralization tests showed that the candidate vaccine induced a strong neutralizing antibody response in mice. In this research, we demonstrated that p170-RBD possesses strong antigenicity and immunogenicity and could be a potential candidate for use in future SARS-CoV-2 vaccine development.

Keywords: SARS-CoV-2; hepatitis E virus; recombinant vaccine; virus-like nanoparticles.

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines / genetics
  • COVID-19* / prevention & control
  • Capsid Proteins / genetics
  • Escherichia coli
  • Hepatitis E virus*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins / genetics
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus / chemistry
  • Viral Vaccines* / genetics

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Capsid Proteins
  • COVID-19 Vaccines
  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Viral Vaccines
  • ORF2 protein, Hepatitis E virus