A universal SARS-CoV DNA vaccine inducing highly cross-reactive neutralizing antibodies and T cells

EMBO Mol Med. 2022 Oct 10;14(10):e15821. doi: 10.15252/emmm.202215821. Epub 2022 Sep 2.


New variants in the SARS-CoV-2 pandemic are more contagious (Alpha/Delta), evade neutralizing antibodies (Beta), or both (Omicron). This poses a challenge in vaccine development according to WHO. We designed a more universal SARS-CoV-2 DNA vaccine containing receptor-binding domain loops from the huCoV-19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins. The vaccine induced spike antibodies crossreactive between huCoV-19/WH01, Beta, and Delta spike proteins that neutralized huCoV-19/WH01, Beta, Delta, and Omicron virus in vitro. The vaccine primed nucleoprotein-specific T cells, unlike spike-specific T cells, recognized Bat-CoV sequences. The vaccine protected mice carrying the human ACE2 receptor against lethal infection with the SARS-CoV-2 Beta variant. Interestingly, priming of cross-reactive nucleoprotein-specific T cells alone was 60% protective, verifying observations from humans that T cells protect against lethal disease. This SARS-CoV vaccine induces a uniquely broad and functional immunity that adds to currently used vaccines.

Keywords: DNA vaccine; SARS-CoV-2; in vivo electroporation; preclinical development; universal SARS vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Humans
  • Mice
  • Nucleoproteins
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / genetics
  • T-Lymphocytes
  • Vaccines, DNA* / genetics
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Vaccines* / genetics


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

Supplementary concepts

  • SARS-CoV-2 variants