Scientists have developed mRNA vaccines that produce virus-like nanoparticles inside cells, potentially offering more robust immune responses than current versions. In mouse studies, this approach generated antibody levels up to 28 times higher than standard mRNA vaccines. The innovation could reduce side effects by allowing lower doses while maintaining efficacy.
Traditional vaccines evolved from weakened live viruses, which are effective but risky for those with compromised immune systems, to safer inactivated and protein subunit versions that often yield weaker responses. To address this, researchers embed viral proteins in spherical nanoparticles that mimic viruses, enhancing immune recognition without the dangers of live pathogens.
During the covid-19 pandemic, a protein-based nanoparticle vaccine called Skycovion was approved in South Korea in 2022. However, mRNA vaccines like those for covid-19 gained prominence due to their rapid and cost-effective production, as they provide genetic instructions for cells to manufacture viral proteins. These proteins protrude from cell surfaces, improving responses over free-floating proteins but falling short of nanoparticle efficacy.
Grace Hendricks at the University of Washington in Seattle and her team combined these strengths by engineering mRNA to code for Skycovion components. Injected into mice, the mRNA prompted cells to assemble nanoparticles internally, resulting in an immune response up to 28 times stronger than conventional mRNA vaccines. Side effects, caused by reactions to mRNA and lipid particles, could be minimized with lower doses. "So the important immune response stays the same, but the side effects would be lower because you gave a smaller dose," Hendricks explained.
"This was just proof of concept of this genetic delivery," she added. The team is now developing similar vaccines against flu, Epstein-Barr virus—which can cause cancers—and other pathogens. William Schief at the Scripps Research Institute expressed enthusiasm: "I am enthusiastic about the promise of mRNA-launched protein nanoparticles for vaccines." His group has seen strong results in clinical trials and mouse models. Despite this progress, the US recently announced significant cuts to mRNA vaccine development funding.
The research was published in Science Translational Medicine (DOI: 10.1126/scitranslmed.adu2085).