Enhanced immunogenicity elicited by a novel DNA vaccine encoding the SARS-CoV-2 S1 protein fused to the optimized flagellin of Salmonella typhimurium in mice

Microbiol Spectr. 2023 Dec 12;11(6):e0254923. doi: 10.1128/spectrum.02549-23. Epub 2023 Nov 1.

Abstract

The development of safe and effective vaccines is needed to control the transmission of coronavirus disease 2019 (COVID-19). Synthetic DNA vaccines represent a promising platform in response to such outbreaks. Here, DNA vaccine candidates were developed using an optimized antibiotic-resistance gene-free asd-pVAX1 vector. An optimized flagellin (FliC) adjuvant was designed by fusion expression to increase the immunogenicity of the S1 antigen. S1 and S1-FliCΔD2D3 proteins were strongly expressed in mammalian cells. The FliCΔD2D3-adjuvanted DNA vaccine induced Th1/Th2-mixed immune responses and high titers of neutralizing antibodies. This study provides crucial information regarding the selection of a safer DNA vector and adjuvant for vaccine development. Our FliCΔD2D3-adjuvanted S1 DNA vaccine is more potent at inducing both humoral and cellular immune responses than S1 alone. This finding provides a new idea for the development of novel DNA vaccines against COVID-19 and could be further applied for the development of other vaccines.

Keywords: DNA vaccine; S1; SARS-CoV-2; antibiotic-resistance gene-free vector; immunogenicity; optimized flagellin adjuvant.

MeSH terms

  • Adjuvants, Immunologic / metabolism
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibodies, Neutralizing / metabolism
  • Antibodies, Viral / metabolism
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Flagellin / genetics
  • Flagellin / metabolism
  • Humans
  • Immunogenicity, Vaccine
  • Mammals
  • Mice
  • SARS-CoV-2
  • Salmonella typhimurium / metabolism
  • Vaccines, DNA* / genetics
  • Vaccines, DNA* / metabolism

Substances

  • Vaccines, DNA
  • Flagellin
  • COVID-19 Vaccines
  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral