COVID-19 DNA vaccine candidates show promise in animals

  • DNA vaccines are an emerging technology with potential advantages over conventional vaccines.
  • The COVID-19 pandemic has focused research on vaccine technologies.
  • In the present paper, researchers demonstrate that COVID-19 DNA vaccines show promise in animal models.

In a new study, a team of researchers demonstrated that DNA vaccines are effective against COVID-19 in mice and hamsters.

The research, which appears in the journal PLOS Neglected Tropical Diseases, lays the ground for further research to determine if the technology can also be effective against COVID-19 in humans.

DNA vaccines

Conventional vaccines use a weakened or inactive pathogen to train a person’s immune system to respond to the pathogen.

However, DNA vaccines deliver part of the genetic information of the pathogen into a person. This then produces the antigens of the pathogen — the substances that trigger a person’s immune system to produce antibodies.

These antibodies can then offer protection against an infection of the full pathogen in the future.

Studies on DNA vaccines emerged in the early 1990s. Initial research demonstrated that it was possible to use plasmid DNA to produce an antibody response.

Researchers were excited because, according to Prof. David B. Weiner, Professor Emeritus at the University of Pennsylvania School of Medicine, and his colleagues, “in theory, DNA vaccines could generate broad immune responses, similar to the live-attenuated virus platform, without the need for a replicating pathogen.”

However, Prof. Weiner and his team note that while early studies offered proof of concept, the results were disappointing. Crucially, the DNA vaccines did not produce effective antibody responses.

A variation on the DNA vaccine is the mRNA vaccine, such as the Pfizer-BioNTech and Moderna COVID-19 vaccines.

Unlike DNA vaccines, mRNA vaccines do not need to reach the cell nucleus to be effective, which researchers believe could increase their effectiveness and mode of application.

However, DNA vaccines have the advantage of being stable at room temperature, making them easier to transport and store — something crucial during a global pandemic such as COVID-19. In contrast, mRNA vaccines require much colder temperatures.

As a consequence, despite the successful deployment of mRNA vaccines in response to the COVID-19 pandemic, there is still much interest in the potential of DNA vaccines.

Animal study

In the present study, the team wanted to investigate the potential efficacy of DNA COVID-19 vaccines. To do so, they conducted an animal study using mice and hamsters.

According to Dr. Shih-Jen Liu, of the National Institute of Infectious Diseases and Vaccinology, Zhunan Township, Taiwan, and the study’s co-authors, “the DNA vaccine is an ideal vaccine platform with several advantages, including easy design and production, stability at a range of temperatures, and low production cost.”

“Hence, the DNA vaccine platform is suitable for rapid and large-scale manufacturing during infectious disease outbreaks.”

To improve the effectiveness of the antibody response that the DNA vaccine produces, the researchers focused on supporting the delivery of the vaccine.

DNA plasmids used in DNA vaccines can degrade quickly, so exploring different delivery methods is necessary to reduce the time it takes for the DNA to enter the nuclei of a person’s cells.

The researchers used a process called electroporation to help increase DNA delivery speed, hoping that this would increase the effectiveness of the antibody response. Electroporation uses electric shocks to insert DNA into cell nuclei.

Effective immune response

The researchers found that DNA vaccine delivery via electroporation induced an immune response against SARS-CoV-2 in mice and hamsters.

The animals produced long-lasting antibodies, which were able to target the spike protein of SARS-CoV-2, reducing the effectiveness of the virus. The antibodies were most prevalent 8 weeks after the animals’ immunization and maintained high levels until 20 weeks following immunization.

After receiving two doses of the DNA vaccine 3 weeks apart, the hamsters gained protection from COVID-19, with fewer signs of SARS-CoV-2 than the hamsters without the vaccinations.

To develop the research, the team suggests exploring different injection techniques. While the scientists used intramuscular injections in the mice, intradermal injections are more convenient for human clinical application because they affect less tissue.

Furthermore, the researchers recommend testing the vaccine’s effectiveness in older mice to reflect the fact that older adults are particularly vulnerable to COVID-19.

If this research is successful, then the researchers believe that “COVID-19 DNA vaccines may play a major role in controlling [the COVID-19 pandemic] in the near future.”

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