The development of DNA vaccines against SARS-CoV-2

Abstract

Background: The COVID-19 pandemic exerted significant impacts on public health and global economy. Research efforts to develop vaccines at warp speed against SARS-CoV-2 led to novel mRNA, viral vectored, and inactivated vaccines being administered. The current COVID-19 vaccines incorporate the full S protein of the SARS-CoV-2 Wuhan strain but rapidly emerging variants of concern (VOCs) have led to significant reductions in protective efficacies. There is an urgent need to develop next-generation vaccines which could effectively prevent COVID-19.

Methods: PubMed and Google Scholar were systematically reviewed for peer-reviewed papers up to January 2023.

Results: A promising solution to the problem of emerging variants is a DNA vaccine platform since it can be easily modified. Besides expressing whole protein antigens, DNA vaccines can also be constructed to include specific nucleotide genes encoding highly conserved and immunogenic epitopes from the S protein as well as from other structural/non-structural proteins to develop effective vaccines against VOCs. DNA vaccines are associated with low transfection efficiencies which could be enhanced by chemical, genetic, and molecular adjuvants as well as delivery systems.

Conclusions: The DNA vaccine platform offers a promising solution to the design of effective vaccines. The challenge of limited immunogenicity in humans might be solved through the use of genetic modifications such as the addition of nuclear localization signal (NLS) peptide gene, strong promoters, MARs, introns, TLR agonists, CD40L, and the development of appropriate delivery systems utilizing nanoparticles to increase uptake by APCs in enhancing the induction of potent immune responses.

Keywords: DNA vaccine; Plasmid design; SARS-CoV-2; Vaccine efficacy; Variants.

Fig. 1

The elicitation of humoral and cellular responses to DNA vaccines. CD4⁺ T cells, such as T follicular helper (Tfh) and Foxp3⁺ T follicular regulatory (Tfr) cells, provide specialized assistance and serve as important mediators towards the formation of germinal centre B cells through T and B cell interactions. Tfh cells also provide help to B cells through CD40L– CD40 interactions, and lead to the release of cytokines (IL-2, IL-4, and IL-21, IFN-γ). Stimulation by cytokines further promotes germination centre formation, and maturation into plasma cells which produce memory B cells and long-lived antibody secreting plasma cells. CD8⁺ T cells directly target and kill infected cells through the production of perforin and granyzymes, limiting the spread of the pathogen within the body [7,8]. Fig. 1 was produced using the graphical software Biorender (https://www.biorender.com/).