Rapid development of a synthetic DNA vaccine for COVID-19

Authors: Smith et al.              

Link to paper:  https://www.researchsquare.com/article/rs-16261/v1

Journal/ Pre-Print: Researchsquare    

Summary

This study tests the efficacy of existing synthetic plasmid DNA (pDNA) backbone-based vaccine technology against the SARS-Cov-2 spike protein that contains the receptor binding domain (RBD) of the virus. Vaccines against the analogue spike in SARS-Cov are already being clinically tested. In this study, the authors use the same plasmid backbone to develop a SARS-Cov-2 vaccine. The vaccine is administered intramuscularly into mice and guinea pigs by electroporation. In both species there is a measurable humoral response against recombinant spike protein after 14 days. T cell response was also detected in mice with ELISpot against SARS-Cov-2 peptides.

Research highlights 

  1. pDNA vaccines can elicit humoral responses against recombinant SARS-Cov-2 spike in small rodents.
  2. pDNA vaccines can elicit cellular response against recombinant SARS-Cov-2 spike in mice.
  3. pDNA vaccines with the same plasmid backbones have already been tested in humans.

Research Impact:

For development of a SARS-Cov-2 vaccine that can be rapidly produced at scale

Methodology:

DNA vaccine development (plasmid cloning)

In vitro RNA expression

In vitro protein expression (Western blot, immunofluorescence)

In vivo (mice and guinea pigs) electroporation

Antigen binding assay (ELISA)

Cell activation assay (ELISpot)

Strengths and weaknesses of the paper:

Strengths:

Quality of the assays

Easily reproducible

Feasible as there are similar vaccines already in the clinic

Weaknesses:

Intramuscular delivery system requires special device

Low number of animals used

Conflict of interest: Coalition for Epidemic Preparedness Innovations (CEPI)

Using recombinant protein instead of the virus

No infection outcome readout