DNA vaccines for SARS-CoV-2: toward third-generation vaccination era

Abstract

Introduction: Coronavirus outbreak 2019 (COVID-19) has affected all the corners of the globe and created chaos to human life. In order to put some control on the pandemic, vaccines are urgently required that are safe, cost effective, easy to produce, and most importantly induce appropriate immune responses and protection against viral infection. DNA vaccines possess all these features and are promising candidates for providing protection against SARS-CoV-2.Area covered: Current understanding and advances in DNA vaccines toward COVID-19, especially those under various stages of clinical trials.Expert opinion: Through DNA vaccines, host cells are momentarily transformed into factories that produce proteins of the SARS-CoV-2. The host immune system detects these proteins to develop antibodies that neutralize and prevent the infection. This vaccine platform has additional benefits compared to traditional vaccination strategies like strong cellular immune response, higher safety margin, a simple production process as per cGMP norms, lack of any infectious agent, and a robust platform for large-scale production.

Keywords: COVID-19; DNA vaccine; SARS-CoV-2; genetic vaccine; immunization; nucleotide vaccines; pandemic; vaccine.

Figure 1.

The genomic organization of SARS-CoV-2 and spike protein structure. (1) The structure of SARS-CoV-2 containing an RNA as genetic material with four distinguished structural proteins like spike glycoprotein (S), membrane protein (M), envelop protein (E), and nucleocapsid (N), (2) the genomic organization of the SARS-CoV-2 with 16 Nsps along with the structural and the accessory proteins gene (from 5ʹ end to 3ʹ end), and (3) spike glycoprotein structure with two subunits S1 and S2 that are targeted by the human enzyme Furin, and it may also cause the development of a syncytium (cell fusion) where S1 contains a receptor binding domain (RBD); S1 has a C-terminal domain (CTD) and an N-terminal domain (NTD)

Figure 2.

Mechanism of action of DNA based vaccines for SARS-CoV-2. To make the DNA vaccine, single-stranded RNA (ssRNA) of SARS-CoV-2 spike protein (as an example) is extracted, synthesized into double-stranded (dsDNA), and cloned into a plasmid. This plasmid is then injected intramuscularly in conjunction with an electroporation device to facilitate uptake. Within the muscles, myocytes take up the plasmid and express the protein of interest. This will lead to either CD8 + T cell activation through MHC class I or B cell activation. Antigen presenting cells like macrophages will endocytose spike proteins from necrotizing myocytes and activate CD4 + T cells through MHC class II presentation. Overall, leading to the recruitment of multiple immune subsets