Inovio Pharmaceuticals Inc (INO)

[Opus X]

DNA-Based Vaccines
DNA vaccine, yet another type of nucleic acid vaccine, is made from DNA encoding antigen protein. Unlike traditional vaccines, DNA vaccines are designed to inject a specific naked DNA code of the pathogen directly into the human body (219, 238). Once inside, it can be transcribed into mRNA in the nucleus and translated into antigen in the cytoplasm, thereby inducing the body to produce an immune response (239). Thus, vaccinated individuals obtain corresponding immune protection and disease prevention capabilities (240). Interestingly, its rapid technological development may create a whole new generation of immunologic tools. Multiple DNA vaccines are currently under development, including malaria, influenza, rotavirus, HIV, and so on. Furthermore, many of them have already entered CTs (241–243). DNA vaccination offers more potential advantages, compared to traditional vaccines, including stimulation of the B and T cell immune responses, stabilization of the vaccine, avoidance of any infectious agents, and ease of large scale production (244). More importantly, a large-scale COVID-19 vaccination is under rapid execution around the world, and the “stability” that determines whether a vaccine is convenient for transportation, and storage is a major indicator of vaccine feasibility (245). Compared to RNA vaccines, DNA vaccines can be stored for a longer period of time at the same refrigeration temperature, or even for a longer time at room temperature (246). Once successfully developed and put into use, this will likely bring great convenience to the mass production of vaccines. However, DNA vaccines usually exhibit low immunogenicity, and must be inoculated through delivery devices (such as, electric perforators) to be effective, which also limits their use.

Due to the COVID-19 pandemic outbreak, numerous DNA vaccine candidates entered CTs. According to the information from ICTRP, three of them entered phase III CTs, namely INO-4800, AG0302-COVID19, and, ZyCoV-D. INO-4800, developed by INOVIO Pharmaceuticals, is a DNA vaccine candidate for the prevention of the new coronavirus (243, 247). After the new coronavirus gene sequence was released, INOVIO employed a proprietary DNA drug platform to quickly design the INO-4800 vaccine (247). Pre-CT revealed that INO-4800 strongly induces SARS-CoV-2 specific antibody and T cell responses in mice and guinea pigs, hence, it was quickly approved for CTs (248). Based on the phase I CT results, INO-4800 is immunogenic in all subjects, and effectively produces humoral immune and/or cellular responses (145). Currently, the INO-4800 vaccine is simultaneously in both phase II/III CTs, and its safety and effectiveness reports are worthy of attention. AG0301-COVID19, a DNA vaccine developed by Osaka University/AnGes/Takara Bio, expresses the full-length S protein upon host cell entry. In a pre-CT, AG0301-COVID19, with an aluminium-containing adjuvant, strongly stimulated neutralizing antibody production, and enhanced T cell responses in rats, with no toxic response to body organs. Yet another COVID-19 DNA vaccine candidate is AG0301-COVID19, also developed by the Osaka University/AnGes/Takara Bio. The safety and effectiveness of the AG0301-COVID19 vaccine was examined in phase I/II CTs, but the results are not yet reported (243). It is worth noting that the phase III CTs are in progress at the present time. Recently, India urgently authorized and approved the listing of a DNA COVID-19 vaccine ZyCov-D that consists of a DNA plasmid vector harboring the S protein genetic code. A pre-CT study revealed that ZyCov-D elicits marked antibody and Th-1 responses, as demonstrated by augmented IFN-c expression (249). In a phase I CT, the ZyCov-D vaccine, which is administered by pressing a needle-free device on the skin, was reported to be safe, well tolerated, and immunogenic (142). The device creates a tiny stream of high-pressure liquid that pierces the skin surface, thus causing less pain for the recipient. ZycoV-D is currently conducting a large-scale phase III CT in India, involving tens of thousands of subjects, but the data is not public yet. However, due to its high efficiency and safety, India urgently authorized the application of ZycoV-D. Thus far, this is not only the first DNA vaccine for COVID-19, but also the first DNA vaccine in the world. Till date, no DNA vaccine completed phase III trials or received approval.

https://www.frontiersin.org/articles/10.3389/fimmu.2022.843928/full