A novel DNA and protein combination COVID-19 vaccine formulation provides full protection against SARS-CoV-2 in rhesus macaques

Emerg Microbes Infect. 2021 Dec;10(1):342-355. doi: 10.1080/22221751.2021.1887767.

Abstract

The current study aims to develop a safe and highly immunogenic COVID-19 vaccine. The novel combination of a DNA vaccine encoding the full-length Spike (S) protein of SARS-CoV-2 and a recombinant S1 protein vaccine induced high level neutralizing antibody and T cell immune responses in both small and large animal models. More significantly, the co-delivery of DNA and protein components at the same time elicited full protection against intratracheal challenge of SARS-CoV-2 viruses in immunized rhesus macaques. As both DNA and protein vaccines have been proven safe in previous human studies, and DNA vaccines are capable of eliciting germinal center B cell development, which is critical for high-affinity memory B cell responses, the DNA and protein co-delivery vaccine approach has great potential to serve as a safe and effective approach to develop COVID-19 vaccines that provide long-term protection.

Keywords: DNA vaccine; SARS-CoV-2; non-human primate; protein vaccine; spike glycoprotein.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / immunology*
  • Cell Line
  • DNA / immunology
  • HEK293 Cells
  • Humans
  • Lymphocyte Count
  • Macaca mulatta
  • Mice
  • Mice, Inbred C57BL
  • Plasmids / genetics
  • Rabbits
  • Recombinant Proteins / immunology
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology
  • Spike Glycoprotein, Coronavirus / immunology*
  • T-Lymphocytes / immunology
  • Vaccines, DNA / immunology*
  • Vaccines, Subunit / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • Vaccines, DNA
  • Vaccines, Subunit
  • spike protein, SARS-CoV-2
  • DNA

Grants and funding

This work was supported by the Major Science and Technology Projects of Yunnan Province [grant numbers 2019ZF001, 202003AC100003, 202003AF140002]; CAMS Initiative for Innovative Medicine [grant number 2016-I2M-1-019]; Fundamental Research Funds for the Central Universities [grant number 2020HY320001].