A new generation of vaccines: Combining design and delivery
In the wake of the COVID-19 pandemic, two vaccine technologies stood out – mRNA vaccines like those from Pfizer and Moderna, and protein nanoparticle vaccines such as those designed by computational biologists. Each offered something valuable: mRNA vaccines could be produced rapidly and triggered strong cellular responses, while protein nanoparticles excelled at presenting antigens in ways that generated potent antibodies.
What if this could be combined into a single platform – a vaccine that is not only fast to produce but also highly effective in training the immune system?
That’s exactly what scientists from the University of Washington’s Institute for Protein Design, in collaboration with teams at Stanford University, UNC Chapel Hill, and Acuitas Therapeutics, set out to achieve. Their work, published in Science Translational Medicine (October 2025), introduces the concept of “mRNA-launched protein nanoparticles”, a hybrid vaccine platform that merges the strengths of both approaches.
The Idea: Let Cells Build the Nanoparticles
Traditional protein nanoparticle vaccines are manufactured in the lab and then injected as purified proteins. In contrast, Hendricks and colleagues explored whether the body’s own cells could assemble these nanoparticles directly from mRNA instructions, much like how current mRNA vaccines teach cells to make viral proteins.
They started by designing a self-assembling protein scaffold, called I3-01NS, optimized for secretion from human cells. Onto this scaffold, they attached a stabilized version of the SARS-CoV-2 receptor binding domain; the part of the virus that attaches to human cells. When cells read the mRNA for this design, they secreted complete nanoparticles displaying 60 copies of the receptor binding domain in an ordered array, a structure known to enhance immune recognition.
The Results: Stronger, Broader Immune Responses
In mouse studies, the mRNA-launched nanoparticles produced 5- to 28-fold higher neutralizing antibody levels than either standard mRNA vaccines or protein-based counterparts. They also triggered robust CD8 T-cell responses, showing the benefit of intracellular antigen production typical of mRNA vaccines.
When challenged with the original Wuhan-Hu-1 and Omicron BA.5 variants of SARS-CoV-2, vaccinated mice showed strong protection, little to no weight loss, reduced lung inflammation, and in many cases, no detectable virus in the lungs.
Beyond SARS-CoV-2, the researchers demonstrated that the same nanoparticle scaffold could display antigens from other viruses, including SARS-CoV-1, bat coronaviruses, and even engineered HIV fragments, suggesting broad potential for future vaccines.
Why It Matters
This study represents an early proof of concept that computational protein design can be paired with genetic delivery systems to produce vaccines that are both powerful and adaptable. By encoding complex, self-assembling nanoparticles as mRNA, vaccine developers could one day respond to emerging pathogens with more speed and precision.
Read more here: https://www.science.org/doi/10.1126/scitranslmed.adu2085