Advances in DNA vaccines against COVID-19

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

The rapid spread of the pathogen and the growing number of cases underscore the need for an effective and safe vaccine. As vaccination efforts expand in many countries, new types of vaccines, such as deoxyribonucleic acid (DNA) vaccines, are being researched.

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

The study is published in the journal Life sciences.

What is a DNA vaccine?

Among the technologies available for vaccine development, DNA vaccination is an alternative to traditional vaccines. Discovered in the 1990s, these vaccines have aroused the interest of scientists around the world because of their ability to trigger humoral and cellular immune responses.

In this type of vaccine, a gene from a virus or bacteria is used to stimulate the immune system. When the DNA vaccine is administered to a patient, the machinery of their cells 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 disease.

The basic working principle of DNA vaccines is to use a DNA plasmid that encodes a protein from the pathogen, in this case, SARS-CoV-2. Plasmid DNA (pDNA) is inexpensive, stable, and secure, which makes the non-viral platform considered a good option for gene delivery.

DNA vaccines in clinical evaluation

When SARS-CoV-2 appeared in late December 2019, many scientists began to study the genome of the virus. In January 2020, the complete genome of the virus was published. To develop effective vaccines, it is essential to understand the structure of the virus genome.

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

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

A total of 250 vaccines are under development to fight the coronavirus pandemic. Of these, 181 are in preclinical development, while 69 are under clinical evaluation.

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

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

One of the vaccines, called AG0301-COVID-19, uses a schedule of two immunizations, the first with a low dose and then a high dose. The two injections are given intramuscularly over a two week interval.

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

In the phase 1 human trial of the vaccine, it was administered intradermally by electroporation. In this trial, the vaccine was shown to induce neutralizing antibodies, blocking the binding of the SARS-CoV-2 S protein to the angiotensin-converting enzyme 2 (ACE2) receptor of the host cell.