Comparison of Wild Type DNA Sequence of Spike Protein from SARS-CoV-2 with Optimized Sequence on The Induction of Protective Responses Against SARS-Cov-2 Challenge in Mouse Model

Hum Vaccin Immunother. 2022 Dec 31;18(1):2016201. doi: 10.1080/21645515.2021.2016201. Epub 2022 Jan 21.

Abstract

Genetic optimization of Nucleic Acid immunogens is important for potentially improving their immune potency. A COVID-19 DNA vaccine is in phase III clinical trial which is based on a promising highly developable technology platform. Here, we show optimization in mice generating a pGX-9501 DNA vaccine encoding full-length spike protein, which results in induction of potent humoral and cellular immune responses, including neutralizing antibodies, that block hACE2-RBD binding of live CoV2 virus in vitro. Optimization resulted in improved induction of cellular immunity by pGX-9501 as demonstrated by increased IFN-γ expression in both CD8+ and CD4 + T cells and this was associated with more robust antiviral CTL responses compared to unoptimized constructs. Vaccination with pGX-9501 induced subsequent protection against virus challenge in a rigorous hACE2 transgenic mouse model. Overall, pGX-9501 is a promising optimized COVID-19 DNA vaccine candidate inducing humoral and cellular immunity contributing to the vaccine's protective effects.

Keywords: COVID-19; DNA vaccine; SARS-CoV-2; optimizations; protective response; spike protein; wild-type sequence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Base Sequence
  • COVID-19* / prevention & control
  • Mice
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus* / genetics

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Grants and funding

This work was supported by the National Natural Science Foundation of China [81991492]; National Natural Science Foundation of China [82041039]; National Key R&D Program of Chinese Ministry of Science & Technology [2018YFC0840402].