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.