The coronavirus infection (COVID-19), caused by the acute respiratory coronavirus 2 (SARS-CoV-2) syndrome, is spreading worldwide. The total number of diseases has reached 109.88 million worldwide with 61.88 million reported as recovered.
The rapid spread of the pathogen and the growing number of cases highlight the need for effective and safe vaccination. As vaccine efforts spread in many countries, new types of vaccines, such as deoxyribonucleic acid (DNA) vaccines, are under investigation.
Researchers at the Department of Pharmacy, Pelotas, Rio Grande do Sul, in Brazil, explained the potential and effectiveness of DNA vaccines in pandemic situations. They also provided a summary of the DNA vaccines tested in clinical trials.
The study is published in the journal Life sciences.
What is a DNA vaccine?
Technologies available for vaccine development include DNA vaccination as an alternative to traditional vaccines. Discovered in the 1990s, these vaccines have piqued the interest of scientists worldwide because of their ability to suppress humoral and cellular immune responses.
In this type of vaccine, a gene from a virus or bacterial is used to stimulate the immune system. When a patient is given the DNA vaccine, their cellular machinery produces viral or bacterial proteins, which the immune system recognizes as a foreign body. From there, the immune system remembers the foreign body and finds it the next time it enters the body, preventing illness.
The basic working principle behind DNA vaccines involves the use of a DNA plasmid encoding for proteins derived from the pathogen, in this case, SARS-CoV-2. Plasmid DNA (pDNA) is cheap, stable and secure, allowing the non-viral platform to be considered a good choice for gene delivery.
DNA vaccines in clinical evaluation
When SARS-CoV-2 appeared in late December 2019, many scientists began studying the genome of the virus. By January 2020, the full strain of the virus was revealed. To develop effective vaccines, it is essential to understand the genome structure of the virus.
During infection, antibodies are stimulated and excreted against both N and S proteins of the virus. The N protein encodes the viral genome and is involved in the release of viral granules into cells. At the same time, the S protein plays a crucial role in pathogenesis by binding to the host cell through its receptor binding domain (RBD). It initiates the disease process by allowing the virus to enter the host cell for invasion and reproduction.
All DNA vaccines tested in clinical trials for COVID-19 use S protein as the antigen.
In total, 250 vaccines are being developed to combat coronavirus pandemic. Of these, 181 are in preclinical development, and 69 are undergoing clinical evaluation.
Vaccines in clinical evaluation include ten DNA – based vaccines. These include one vaccine in a phase 3 trial, the nCoV vaccine by Zydus Cadila. Vaccines at stage 2/3 test include electroporation INO-4800 + by Inovio Pharmaceuticals and vaccine AG0301-COVID19 by AnGes University / Takara Bio / Osaka. The DNA-based vaccine under phase 1/2 test includes the GX-19 vaccine with the Genexine Consortium.
At the same time, the Covigenix VAX-001 vaccine was acquired by Entos Pharmaceuticals Inc., CORVax – Plasmid Spike Protein (S) DNA Vaccine by Providence Health & Services, the bacTRL-Spike oral DNA vaccine by Symvivo Corporation, GLS-5310 vaccine by GeneOne Life Science, Inc., Covigen vaccine is owned by the University of Sydney, Bionet Co. and Technovalia, and the COVID-eVax by Takis / Rottapharm Biotech in phase 1 human trials.
One of the vaccines, called AG0301-COVID-19, uses a two-vaccine scheme, first with a low dose and then a high dose. Both images are administered intramuscularly within two weeks.
Another vaccine, the electroporation INO-4800 +, was developed by Inovio Pharmaceuticals, which has previously developed experimental vaccines against Middle Eastern respiratory coronavirus syndrome (MERS-CoV). The current vaccine against COVID-19 induced both cellular and humoral immune responses seen within days after a single vaccination in mice and guinea pigs during the his preclinical test.
During a phase 1 human trial of the vaccine, it was administered intradermally by electroporation. In this experiment, the vaccine showed that it stimulated the uptake of antibodies, inhibiting the binding of SARS-CoV-2 S protein to the angiotensin-converting enzyme 2 (ACE2) cell receptor.
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