DNA vaccines against COVID-19: Perspectives and challenges

Abstract

The coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is associated with several fatal cases worldwide. The rapid spread of this pathogen and the increasing number of cases highlight the urgent development of vaccines. Among the technologies available for vaccine development, DNA vaccination is a promising alternative to conventional vaccines. Since its discovery in the 1990s, it has been of great interest because of its ability to elicit both humoral and cellular immune responses while showing relevant advantages regarding producibility, stability, and storage. This review aimed to summarize the current knowledge and advancements on DNA vaccines against COVID-19, particularly those in clinical trials.

Developmental Status of the Potential Vaccines for the Mitigation of the COVID-19 Pandemic and a Focus on the Effectiveness of the Pfizer-BioNTech and Moderna mRNA Vaccines

“…Indeed, the different categories of COVID-19 vaccines have been elaborately discussed in several reports [ 3 , 6 , 7 , 10 – 12 ]. In this review, the promising candidates which may be commercially applied for the quick mitigation of the disease are deliberated.…”

“…Another promising vaccine developed in Russia (phase III clinical trial), the Gam-COVID-Vac-Lyo vaccine, has been authorized for emergency use [ 6 ]. However, the DNA- and RNA-based approaches possess the greatest potential for escalating the development of effective vaccines in the current dreadful situation caused by the SARS-CoV-2 [ 11 , 12 ]. A glimpse of these most prospective vaccines is given in the succeeding text.…”

“…Descriptively, the mRNA-1273 vaccine (whereby the mRNA encoding the S-2P antigen, containing the SARS-CoV-2 glycoprotein attached to a transmembrane anchor, and an intact S1–S2 cleavage site, and is enclosed by a 4 subunit lipid nanoparticle) which has undergone the first-in-human dose-dependent (25 or 30, 100, and 250 μg), open-label phase II clinical trial NCT04283461 (with the fast-track approval from the USFDA as stated above) successfully detected the elevated neutralizing antibody titers and the required T cell responses [ 3 , 6 , 11 , 13 ]. A unique characteristic of this vaccine is that this one is free from any preservative [ 12 ]. This is also notable that in the current phase III trial, around 44,000 participants are being subjected for the evaluation of the safety and efficacy of the mRNA-1273 (Moderna TX, Inc.) vaccine, and the outcome is 95% satisfactory so far [ 13 ].…”

“…The DNA vaccine, which induces both humoral and cell-mediated immunity, is made on the principle that the genetic material of the SARS-CoV-2 is translocated (the antigen-presenting cells or APCs receive the genetic material) to the host’s cell nucleus so that the mammalian promoter present in the plasmid vector is activated, triggering the transcription and translation of the transfected gene(s) within the host [ 12 ]. The resulting vaccine antigenic protein can then be presented to the APCs (mainly the DCs) through the MHC signaling: (1) the CD8 + T cell immunity is induced by the myocytes (MHC I signaling) which in turn stimulates the excretion of interferon (IFN)-γ and the tumor necrosis factor (TNF)-α, and thus, the viral replication inside the host is hindered (Fig.…”

“…3 ) and ( 2 ) the CD4 + helper T cells are activated by macrophages (MHC II signaling), and the DCs (MHC II signaling) activate the CD8+ T cells by triggering the production of interleukin (IL)-10, IL-12, and the tumor necrosis factor (TNF)-α, and the CD4 + helper T cells are activated by these DCs (Fig. 3 ) when they produce IL-4 [ 12 , 16 , 19 ]. This is to be mentioned that myocytes have been evidently the predominant transfected cell type triggering the potential cell-mediated immunity [ 20 ].…”