Why are the next generation of mRNA vaccines set to be better?

Virus-like vaccines generally produce a stronger immune response, while mRNA transcripts are much faster and cheaper to manufacture. And now we get the best of both worlds, in the form of mRNA vaccines that encode virus-like nanoparticles, not just individual proteins, as is the case with current mRNA vaccines for Covid-19.

Grace Hendricks She and her colleagues at the University of Washington in Seattle showed that an mRNA version of a nanoparticle vaccine for COVID-19 produces an immune response in mice that is up to 28 times higher than that of a standard mRNA vaccine.

Hendricks says some of the unpleasant — but mild — side effects of mRNA vaccines stem from the body’s immediate reaction to the injected mRNA and the liposomes contained in it. With more effective vaccines, the dose can be reduced. “So the important immune response remains the same, but the side effects will be less because you gave a smaller dose,” she says.

The first ever vaccines consist of weakened “live” viruses, which are highly effective but can be dangerous for people with weakened immune systems. Then came inactivated vaccines that contain “dead” viruses, which are safer but difficult to manufacture.

The next advance was protein subunit vaccines, which typically contain only the external proteins of viruses. They are safer than inactivated vaccines, but free-floating proteins tend not to produce a strong immune response.

So, vaccine designers began incorporating viral proteins into tiny domains to create spiked balls that look like a virus to the immune system, but are just as safe as protein subunit vaccines. One way to do this is to modify existing proteins so that they self-assemble into little spheres, with viral proteins coming out of them, known as vaccine nanoparticles.

During the pandemic, Hendrix colleagues created The nanoparticle vaccine for COVID-19 is called Skycovion. It was approved in South Korea in 2022, but by then, mRNA vaccines had already had a big head start, so they were not widely used.

mRNA vaccines are faster and easier to make than protein-based vaccines because they consist of recipes for making proteins, and the cells in our bodies do the hard part of making those proteins. Viral proteins encoded by first-generation messenger RNA (mRNA) vaccines end up protruding from outside cells and produce a better immune response than free-floating proteins, but they are not as effective as nanoparticle vaccines.

Now, Hendricks and her colleagues have combined the advantages of both approaches by creating a vaccine consisting of mRNAs encoding Skycovion. When the vaccine proteins are made inside cells, they assemble into nanoparticles, with signs of their effectiveness in a study in mice.

“This was just a proof of concept for gene delivery,” Hendricks says. She and her colleagues are already working on mRNA nanoparticle vaccines, as they call them, against Epstein-Barr influenza — which can cause cancer — and other viruses.

“I am excited about the promise that mRNA-released protein nanoparticles offer for vaccines,” he says. William Schiff At the Scripps Research Institute in California, which is developing HIV vaccines. “My colleagues and I have published impressive results in immunology using two mRNA-released nanoparticles in clinical trials and several of these nanoparticles in mouse models. This new paper adds nicely to the body of work.” But despite the potential of mRNA vaccines, the United States recently announced significant cuts in funding for their development.

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