DNA vaccines are a third-generation technology that uses engineered genetic material to stimulate an immune response. Instead of injecting a weakened pathogen, this approach provides the body’s cells with instructions to produce a specific, harmless part of one. The immune system then learns to recognize this part, preparing it to fight a future infection without exposure to the live agent.
The Mechanism of DNA Vaccines
The core component of a DNA vaccine is a plasmid, a small, circular piece of DNA engineered in a lab. This plasmid carries a gene that codes for a specific antigen—a protein from a pathogen. The plasmid is derived from bacteria but is modified so it cannot cause disease or replicate in human cells, serving only as a vehicle for the genetic instructions.
To get the plasmid into the body’s cells, it is typically injected into muscle tissue, though this alone results in limited uptake. To enhance delivery, a technique called electroporation is frequently used. After the injection, brief, controlled electrical pulses are applied to the site, which creates temporary pores in cell membranes. This allows the plasmids to enter cells more effectively, increasing uptake by 100 to 1,000 times compared to injection alone.
Once inside a host cell, the plasmid travels to the nucleus. There, the cell’s machinery reads the plasmid’s DNA and transcribes it into a messenger RNA (mRNA) molecule. This mRNA then moves to the cytoplasm, where it is translated by ribosomes to produce the specified antigen protein.
These new antigen proteins are presented on the surface of the host cell, where immune cells like T-cells recognize them as foreign. This triggers a full immune response, including the production of antibodies by B-cells and the creation of memory cells. This process builds immunological memory, enabling the body to quickly neutralize the pathogen upon future exposure.
Comparison to Other Vaccine Platforms
DNA vaccines differ from traditional types, like live-attenuated or inactivated vaccines, which introduce a weakened or killed pathogen. Instead of the pathogen itself, DNA vaccines provide only genetic instructions for an antigen, meaning there is no exposure to infectious components. This also provides manufacturing advantages, as producing plasmids is a cell-free process that creates a more heat-stable product.
Like mRNA vaccines, DNA vaccines use genetic instructions to have the body produce antigens. The primary difference is the nucleic acid’s path within the cell. DNA vaccines use deoxyribonucleic acid (DNA), which must enter the cell’s nucleus to be transcribed into mRNA before it can be translated into the antigen protein in the cytoplasm.
Conversely, mRNA vaccines deliver messenger RNA directly to the cytoplasm, bypassing the nucleus. This makes the process one step shorter, as the instructions are immediately ready for translation. While DNA is a more stable molecule, the direct action of mRNA can lead to faster production of the target antigen.
The Safety Profile of DNA Vaccines
A common question is whether the injected plasmid can integrate into a person’s DNA. The risk is exceedingly low due to multiple biological safeguards. The plasmid DNA is circular, lacks the integrase enzyme required for insertion, and must cross the significant barrier of the nuclear membrane to reach the host’s chromosomes.
Extensive studies have evaluated this risk, showing that plasmid DNA remains almost entirely separate from the host cell’s genome. While it can be detected in muscle tissue for months, the frequency of potential integration is estimated to be far below the natural rate of spontaneous gene mutation. These findings confirm the risk of genetic modification is negligible.
Like all medical products, DNA vaccines undergo extensive testing in multi-phase clinical trials before approval. These trials monitor for all potential adverse effects, not just genomic integration but also the body’s response to the foreign plasmid DNA itself. This includes checking for the possibility of inducing immune tolerance rather than activation, and regulatory bodies have strict guidelines to assess safety.
Current and Future Applications
DNA vaccine technology is established in veterinary medicine, providing a strong proof of concept for its effectiveness in mammals. Notable examples include a vaccine to protect horses from West Nile virus and a therapeutic vaccine for malignant melanoma in dogs. These approved products demonstrate the technology can safely induce a protective immune response.
While no DNA vaccines are broadly approved for human use in the U.S. or Europe, one vaccine, ZyCoV-D, received emergency use authorization in India for COVID-19. This was the first DNA vaccine authorized for humans. The platform remains a focus of research for diseases that are challenging to target with other vaccine approaches.
The future of DNA vaccines in human medicine is focused on persistent global health challenges. The platform’s ability to generate strong T-cell responses is a considerable advantage for targeting complex diseases. Researchers are actively developing DNA vaccines for:
- Cancer immunotherapy, to train the immune system to recognize and attack tumor cells
- Human Immunodeficiency Virus (HIV)
- Zika virus
- Influenza