Since the development of the first successful smallpox vaccine introduced by physician Edward Jenner in 1796, humans have benefited from vaccines for more than two centuries. As the COVID-19 pandemic sweeps through every corner of the world, one of the most pressing questions has been the possibility of a vaccine as a solution to prevent the spread of this fatal virus.
Prevention is the most foolproof method of medical intervention and is the signature move of public health departments everywhere. Other traditional methods involve prevention or mitigation and involve things like clean water, sanitation or the wearing of masks. Vaccines are the first line of defense against diseases. In most cases, just one administration of a vaccine is enough to provide lifetime protection against a certain disease. In recent years vaccinology has evolved from using attenuated live viruses to harnessing the power of genetic engineering. DNA vaccination, a combination of technology and biology, is emerging as a new chapter in immunology.
While DNA vaccines are certainly advantageous in many ways, having improved stability, the ability to be administered without risking infection and cheaper manufacturing on a larger scale, there are also certain concerns that they pose.
As Dr. Paul Church, Upper School Science Department Chair, noted, “There have not yet been any DNA based vaccines approved for use in humans. Therefore, unlike ‘conventional vaccines’, there is no large-scale or long-term evaluation of their effectiveness or possible complications. It is possible that the foreign DNA introduced via the vaccine would integrate into the individual’s genome and the ramifications of this are unknown. In addition, it is important to remember that viruses evolve at a rapid pace. Since a DNA vaccine would only reproduce a small part of the virus, this increases the possibility that multiple boosters or multiple types of vaccines may be required to deliver long term immunity.”
DNA vaccination has proven effective in Phase 2 clinical trials for both SARS and MERS. SARS-CoV-2, the virus that causes COVID-19, shares an almost identical homology with SARS. This poses the question: will a DNA vaccine also be effective in battling SARS-CoV-2? INOVIO, a pioneer in the development of synthetic DNA products, believes that their DNA vaccine, INO-4800, provides the answer according to a study on the Immunogenicity of a DNA vaccine candidate for COVID-19.
According to WHO, DNA vaccines induce immune responses against recombinant antigens encoded by genetically engineered DNA plasmids. A circle of engineered DNA is delivered into cells that read the viral gene and use the mRNA to assemble viral proteins. These proteins are displayed on the cell’s surface and are detected and fought against by the immune system. INOVIO used this approach and successfully induced immunity in mice and guinea pigs. Two types of cells, COS-7 and HEK-293T were transfected by INOVIO scientists to express the spike protein of SARS-CoV-2. These cells were chosen for their high transfection efficiency and their ability to rapidly produce protein copies. Mice and guinea pigs were immunized with these transfected cells. IgG levels in sera and lung fluid were monitored for up to 6 weeks.
The trials were successful. High levels of IgG were found in both sera and lung washes. In addition, T cell responses against SARS-CoV-2 were observed as early as day 7 post-vaccine delivery. This could potentially lower viral load, thus reducing viral spread. INOVIO scientists concluded that the INO-4800 vaccine induces successful cellular and immune responses against SARS-CoV-2.
These promising results support further studies to advance the development of INO-4800 in response to the COVID-19 global health crisis. On October 29, WHO published a DRAFT landscape of 45 candidate vaccines, including INOVIO’s INO-4800. If INO-4800 is successful in the prevention of the spread of COVID-19, DNA vaccines will take the center stage of the battle against infectious disease.
