6.4 DNA vaccines
A typical DNA vaccine is a plasmid DNA molecule which encodes for one or
multiple antigens to be presented to the host immune system. They
possess the advantages of stability and efficient delivery over mRNA
vaccines but they possess the risk of vector mutations and integration
into the host genome because they are required to enter the nucleus
(Zhang et al., 2020; Liu 2019; Rauch et al., 2018). DNA vaccines
targeting the antigenic fragments such as S, N, M, and E proteins of
SARS-CoV have been evaluated in mice (He et al., 2005b; Jin et al.,
2005; Kim et al., 2004) and the DNA vaccines targeting S, M, and N
proteins induced humoral as well as cellular immune response. However,
variation in the level of immunity between the target proteins was
observed (Jin et al., 2005). An approach of combining different vaccine
strategies is considered superior in eliciting an efficient immune
response and protection against SARS-CoV (Woo et al., 2005; Zakhartchouk
et al., 2005). For example, administration of S protein coding DNA
vaccine, followed by whole virus inactivated vaccine or S peptide
vaccine, elicited more powerful humoral and cell-mediated immune
responses in mice than either type alone (Roper and Rehm, 2009; Enjuanes
et al., 2008; Zakhartchouk et al., 2005; Woo et al., 2005). The DNA
vaccines are considered safe, stable, and can be produced rapidly but
their immunogenicity and efficiency of eliciting immune response in
humans has not been proven yet. The strategy of DNA vaccination was
initiated in 1993 with promising results against influenza viruses but
the same results could not be translated in humans yet (Chen et al.,
2020). However, several biotech companies with advanced nucleic acid
vaccine platforms, such as Inovio Pharmaceuticals, Applied DNA Sciences
Subsidiary, LineaRx, and Takis Biotech have taken up DNA vaccine
development against COVID-19 (Chen et al., 2020; Zhang et al., 2020).
There are two DNA vaccines under process of development against
COVID-19. The DNA vaccine candidate, INO-4800, developed by Inovio
Pharmaceuticals is in phase I clinical trials in the US and phase II
clinical trials are expected this summer. Similarly, a linear DNA
vaccine candidate against SARS-CoV-2, developed as result of
collaboration between Applied DNA Science Subsidiary, LineaRx, and Takis
Biotech, is in preclinical stage.