Vaccine disguised as a virus tricks the body into stronger immunity

During the COVID-19 pandemic, it wasn’t just face masks that became part of everyday conversation - so did a new vaccine technology: the mRNA vaccine.

As the first of its kind, the COVID-19 vaccine was developed using mRNA technology, which proved both highly effective against the virus and quick to adapt to new variants. However, the immunity provided by mRNA vaccines tends to wane rapidly, leaving people vulnerable to reinfection just months after vaccination.

Now, a team of researchers may have found a solution.

In a new study published in Nature Nanotechnology, scientists from the University of Copenhagen and the biotech company AdaptVac - originally a spinout from the university - show that mice develop a stronger and longer-lasting immune response when the mRNA vaccine is disguised as virus-like particles. Read the full study here.

“Our study combines two technologies: mRNA vaccines and what we call virus-like particles. By engineering the mRNA vaccine to produce virus-like particles, we trick the immune system into thinking it’s encountering a real virus. This triggers a much stronger and more durable immune response in mice, which is exactly what we want,” says lead author Cyrielle Fougeroux, Senior Scientist at AdaptVac.

A Vaccine in viral disguise

The researchers demonstrate that by adding an extra genetic sequence to the existing mRNA vaccine, they can prompt the immune system to mount a more powerful and sustained response. This implies that lower doses may be sufficient, and the study also suggests that the vaccine’s effects last longer.

“We believe this discovery represents a significant improvement to current mRNA technology and could play a major role in the development of next-generation vaccines,” says senior author Adam Sander, Professor at the Department of Immunology and Microbiology at the University of Copenhagen and Scientific Director at AdaptVac.

While it remains to be seen how much the new mRNA vaccine technology can extend immune responses in humans, the mouse studies show a significantly stronger and longer-lasting immunity.

Preparing for the next pandemic

Researchers around the world are working to better prepare for future pandemics. mRNA vaccines are expected to remain a key part of the global response to emerging viruses.

At the University of Copenhagen, Adam Sander and his colleagues are developing a vaccine against the Nipah virus, which is on the WHO’s list of potential future pandemic threats. The new technology is expected to be ready for human testing within the next few years.

“mRNA technology is a powerful tool against a wide range of diseases, but its short-lived effect in humans is a major challenge. If we can use virus-like particles to achieve a stronger and potentially longer-lasting immune response, we’ve made a meaningful improvement to the technology—one that could have a major impact during a pandemic,” says Adam Sander.

In practical terms, this could mean fewer and smaller vaccine doses are needed to maintain immunity - saving both money and healthcare resources.

About the technology and the study

When mRNA vaccines emerged during the COVID-19 pandemic, they marked a major shift from traditional vaccine development. Previously, vaccines were made using lab-produced antigens from either live or inactivated viruses - a slow process that struggles to keep pace with rapidly mutating pathogens.

mRNA vaccines work differently: the antigen is produced inside the body. The vaccine itself consists of a small piece of genetic code - messenger RNA (mRNA) - which the immune system responds to.

In this study, researchers added a second genetic sequence to the classic mRNA vaccine. One sequence instructs the body to produce the vaccine antigen, while the other codes for a virus-like particle. Inside the body’s cells, the two components assemble into virus-like particles with surfaces densely coated in the vaccine antigen.

To the immune system, the result looks like a real virus - triggering a stronger immune response.

The study was published in Nature Nanotechnology and conducted in collaboration between the Department of Immunology and Microbiology at the University of Copenhagen and AdaptVac, a spinout company from University of Copenhagen. The University of Copenhagen and AdaptVac share equal rights to the study.