Computer generated illustration of a cross section of a lipid nanoparticle carrying viral mRNA (orange strands).
Scientific photo library / Alamy
Vaccine that resemble viruses tend to produce a stronger immune response, while mRNA versions are much faster and cheaper to make. Now we're getting the best of both worlds in the form of mRNA vaccines that encode virus-like nanoparticles rather than just individual proteins, as is the case with existing Covid-19 mRNA vaccines.
Grace Hendricks from the University of Washington in Seattle and her colleagues showed that an mRNA version of a Covid-19 nanoparticle vaccine produced an immune response in mice that was 28 times higher than that of a standard mRNA vaccine.
Some of the unpleasant but mild side effects of mRNA vaccines are due to the body's immediate reaction to the injected mRNA and the fatty particles in which it is encased, Hendricks says. When using more powerful vaccines, the dose can be reduced. “This way, the important immune response will remain the same, but there will be fewer side effects because you've given a lower dose,” she says.
The first vaccines consisted of weakened “live” viruses, which are very effective but can be dangerous for people with weakened immune systems. Then came inactivated vaccines containing “dead” viruses, which are safer but difficult to produce.
The next advance was protein subunit vaccines, which typically contain only the outer proteins of viruses. They are even safer than inactivated vaccines, but free-floating proteins generally do not produce a strong immune response.
So vaccine developers began embedding viral proteins into tiny spheres to create spiky pellets that look like a virus to the immune system but are as safe as protein subunit vaccines. One way to do this is to modify existing proteins so that they self-assemble into tiny beads from which viral proteins protrude, known as vaccine nanoparticles.
During the pandemic, Hendrix's colleagues created Covid-19 nanoparticle vaccine called Skycovion. It was approved in South Korea in 2022, but by then mRNA vaccines already had a big advantage, so they were not widely used.
mRNA vaccines are much faster and easier to make than protein-based vaccines because they consist of recipes for producing proteins and The cells in our body do the heavy lifting of producing these proteins.. The viral proteins encoded by first-generation mRNA vaccines eventually escape cells and produce a better immune response than free-floating proteins, but are not as effective as nanoparticle-based vaccines.
Now Hendricks and her colleagues have combined the benefits of both approaches, creating a vaccine made from mRNA encoding Skycovion. When vaccine proteins are produced inside cells, they assemble into nanoparticles, which showed signs of effectiveness in a mouse study.
“It was just a proof of concept for genetic delivery,” Hendricks says. She and her colleagues are already working on mRNA vaccines, as they call them, for the flu, the Epstein-Barr virus, which can cause cancer, and other viruses.
“I’m excited about the prospects of using mRNA-triggered protein nanoparticles for vaccines,” says William Sheaf at the Scripps Research Institute in California, which HIV vaccine development. “My colleagues and I have published fantastic results on the immunogenicity of two mRNA-triggered nanoparticles in clinical trials and several such nanoparticles in mouse models. This new paper nicely complements the body of work.” But despite the potential of mRNA vaccines, The US recently announced a significant reduction in funding for its developments..
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