Advancements in DNA vaccines against COVID-19

Clinical Trials & Research

The coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread globally. The total number of infections has reached 109.88 million globally with 61.88 million reported as recovered.  

The rapid spread of the pathogen and the increasing number of cases highlight the need for an effective and safe vaccine. As vaccination efforts roll out in many countries, new types of vaccines, like deoxyribonucleic acid (DNA) vaccines, are under research..

Researchers at the Department of Pharmacy, Pelotas, Rio Grande do Sul, in Brazil, explained the functionality and efficacy of DNA vaccines in pandemic scenarios. They also provided a summary of the DNA vaccines being tested in clinical trials.

The study is published in the journal Life Sciences.

What is a DNA vaccine?

Among technologies available for vaccine development, DNA vaccination is an alternative to traditional vaccines. Discovered in the 1990s, these vaccines have gained scientists’ interest across the globe due to their ability to elicit 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 the DNA vaccine is administered to a patient, their cells’ machinery produces a viral or bacterial protein, which the immune system recognizes as a foreign body. From there, the immune system will remember the foreign body and can detect it the next time it enters the body, preventing illness.

The basic working principle behind DNA vaccines involves using a DNA plasmid that encodes for a protein that came from the pathogen, in this case, SARS-CoV-2. Plasmid DNA (pDNA) is inexpensive, stable, and safe, allowing the non-viral platform to be considered a good option for gene delivery.

DNA vaccines in clinical evaluation

When the SARS-CoV-2 emerged in late December 2019, many scientists started to study the virus’s genome. By January 2020, the complete genome of the virus was published. To develop effective vaccines, understanding the virus’s genome structure is essential.

During infection, antibodies are stimulated and produced against both the N and S proteins of the virus. The N protein covers the viral genome and is involved in releasing virus particles in cells. Meanwhile, the S protein plays a pivotal role in pathogenesis by binding to the host cell through its receptor-binding domain (RBD). It kickstarts the infection process by allowing the virus to enter the host cell for invasion and replication.

All DNA vaccines being tested in clinical trials for COVID-19 use the S protein as the antigen.

Overall, there are 250 vaccines in development to combat the coronavirus pandemic. Of these, 181 are in preclinical development, while 69 are undergoing clinical evaluation.

Among the vaccines in clinical evaluation, ten vaccines are DNA-based. Among these, one vaccine is in the phase 3 trial, the nCoV vaccine by Zydus Cadila. Vaccines at the phase 2/3 trial stage include the INO-4800+electroporation by Inovio Pharmaceuticals and the AG0301-COVID19 vaccine by AnGes/Takara Bio/Osaka University. The DNA-based vaccine under the phase 1/2 trial includes the GX-19 vaccine by Genexine Consortium.

Meanwhile, the Covigenix VAX-001 vaccine by Entos Pharmaceuticals Inc., CORVax – Spike (S) Protein Plasmid DNA Vaccine by Providence Health & Services, bacTRL-Spike oral DNA vaccine by Symvivo Corporation, GLS-5310 vaccine by GeneOne Life Science, Inc., Covigen vaccine by the University of Sydney, Bionet Co. and Technovalia, and the COVID-eVax by Takis/Rottapharm Biotech is in phase 1 human trials.

One of the vaccines, called AG0301-COVID-19, uses a two-immunization scheme, the first with a low dose and then a high dose. Both shots are administered through the intramuscular route within a two-week interval.

Another vaccine, the INO-4800+electroporation, was developed by Inovio Pharmaceuticals, which has previously developed experimental vaccines against the Middle East respiratory syndrome coronavirus (MERS-CoV). The current vaccine against COVID-19 induced both cellular and humoral immune responses observed within days after a single immunization in mice and guinea pigs during its preclinical testing.

During the vaccine’s phase 1 human trial, it was administered intradermally through electroporation. In this trial, the vaccine showed that it induced neutralizing antibodies, blocking SARS-CoV-2 S protein binding to the host cell angiotensin-converting enzyme 2 (ACE2) receptor.

Journal reference:

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