DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice

Sci Rep. 2021 Feb 4;11(1):3125. doi: 10.1038/s41598-021-82498-5.

Abstract

The outbreak of the SARS-CoV-2 virus and its rapid spread into a global pandemic made the urgent development of scalable vaccines to prevent coronavirus disease (COVID-19) a global health and economic imperative. Here, we characterized and compared the immunogenicity of two alphavirus-based DNA-launched self-replicating (DREP) vaccine candidates encoding either SARS-CoV-2 spike glycoprotein (DREP-S) or a spike ectodomain trimer stabilized in prefusion conformation (DREP-Secto). We observed that the two DREP constructs were immunogenic in mice inducing both binding and neutralizing antibodies as well as T cell responses. Interestingly, the DREP coding for the unmodified spike turned out to be more potent vaccine candidate, eliciting high titers of SARS-CoV-2 specific IgG antibodies that were able to efficiently neutralize pseudotyped virus after a single immunization. In addition, both DREP constructs were able to efficiently prime responses that could be boosted with a heterologous spike protein immunization. These data provide important novel insights into SARS-CoV-2 vaccine design using a rapid response DNA vaccine platform. Moreover, they encourage the use of mixed vaccine modalities as a strategy to combat SARS-CoV-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / immunology*
  • Female
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology*
  • Vaccines, DNA / immunology*

Substances

  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • Vaccines, DNA
  • spike glycoprotein, SARS-CoV