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].