13.1. DNA-based vaccine
DNA vaccine is a relatively novel approach that utilize genetically manipulated DNA to produce microbial antigens. DNA plasmids are common engineered platforms for vaccine production that induced both humoral and cell-mediated immune responses. So, considering the ability of DNA vaccines to induce well-balanced antibody and cellular immune responses, opened a new window towards the use of this platform for therapeutic and preventive purposes (Table 3) [120].
Currently, a patented proposal (WO2005081716) has developed a way to better induce immune responses particularly specific CD8+ T cells against DNA-based vaccines for SARS infection. Accordingly, the gene encoding an endoplasmic reticulum chaperone such as calreticulin, is embedded with the genes encoding at least a SARS-CoV peptide in the feature of chimeric DNA. In this regard, gene gun transferring the gold-entrapped chimeric DNA encoding the calreticulin-nucleocapsid fusion gene into mice induced specific B and T cell responses against considered N protein. Moreover, the vaccinated mice were able to significantly reduce the load of challenging vaccinia vector carrying the SARS N gene. The idea of using immunogens derived from conserved sequences of the MERS-CoV spike protein in DNA-based vaccines against MERS infection was also successful and received a patent point (WO2015081155). As expected, the use of conserved sequences as immunogens stimulated notable neutralizing especially the IgG antibodies as well as CD4+ and CD8+cellular immunities. IL-2, TNF-α and IFNγ were also among the cytokines that showed a corresponding increase in vaccinated animals [121]. INO-4800 is a DNA plasmid (pGX9501)-based vaccine candidate against COVID-19 expressing the full-length SARS-CoV2 S protein and developed by the US Inovio Pharmaceutical company (80). Preclinical studies in multiple animal models revealed the promising immunogenicity and neutralizing antibody induction against SARS-CoV2 S protein by INO-4800 vaccine candidate. Besides, the quality of this vaccine has been confirmed and it is currently undergoing phase ΙΙ/ΙΙΙ clinical trials. Other DNA-based vaccine candidates, including AG0301-COVID19, nCov vaccine, GX-19, Covigenix VAX-001, CORVax and bacTRL-Spike are being evaluated for safety and effectiveness in healthy adults [52].