December 18, 2025

Nanoparticle vaccine strategy could protect against Ebola and other deadly filoviruses Scripps Research scientists turn nanoparticles into virus showcases to help the immune system recognize deadly threats.

December 18, 2025

LA JOLLA, CA Filoviruses get their name from the Latin word filum, meaning thread a reference to their long, filamentous shape. This virus family contains some of the most dangerous pathogens known to science, including Ebola, Sudan, Bundibugyo and Marburg viruses. One reason these viruses remain so deadly is the instability of their surface proteins, which makes them difficult for our immune systems to detect and challenging for researchers to target with treatments or vaccines.

Now, a Nature Communications study (currently an Article-in-Press) from Scripps Research scientists published on December 12, 2025, describes new vaccine candidates designed to protect against multiple filovirus strains. These vaccines display filovirus surface proteins on engineered, self-assembling protein nanoparticles (SApNPs), helping the immune system better recognize and respond to the virus. In mouse studies, the nanoparticles triggered strong antibody responses across several filoviruses, highlighting a promising path toward broader, more effective protection for this dangerous family of viruses.

Filoviruses demand better solutions outbreaks have been devastating, with extremely high mortality rates, says senior author Jiang Zhu, professor in the Department of Integrative Structural and Computational Biology. For the last decade, I've been applying my physics background to master protein design. My goal is to develop a universal design blueprint for every major virus family, so that when a new outbreak occurs, we already have a strategy ready to deploy.

Zhu's next-generation vaccine efforts focus on viral surface glycoproteins the proteins viruses use to enter cells and that the immune system must target for protection. His team uses an approach called rational, structure-based design, which involves studying these glycoproteins in extremely fine detail, engineering stable, well-shaped versions, and carrying them on virus-shaped protein balls the SApNPs that reliably trigger strong immune responses.

The team has already applied this vaccine platform to viruses such as HIV-1, hepatitis C, RSV, hMPV and influenza. Filoviruses were the next major challenge.

Filoviruses such as Ebola virus (EBOV) and Marburg virus (MARV) can cause viral hemorrhagic fever, with fatality rates reaching up to 90%. During the 2013 2016 Ebola epidemic in West Africa, more than 11,000 people died and over 28,000 were infected. While two vaccines are approved for Ebola, no vaccine provides broad protection across the full filovirus family.

This is in part because of filovirus' surface glycoproteins. These proteins are naturally unstable, and their vulnerable regions epitopes are hidden beneath a thick layer of glycans, forming a molecular invisibility cloak. In the pre-fusion state (before the virus enters a cell), this shield makes it difficult for immune cells to recognize the virus. Once the virus fuses with a cell, the glycoprotein refolds into a post-fusion shape, further complicating immune targeting.

In 2021, Zhu's team addressed this problem in a study published in Nature Communications, where they mapped the Ebola glycoprotein structure in detail and developed a strategy to stabilize it. By removing the mucin-rich segments, they created a cleaner, more accessible version of the protein one that was easier for the immune system to detect and capable of generating stronger, more useful antibody responses.

After solving the Ebola problem in 2021, this new work takes that theory further and applies it across additional filovirus species, Zhu explains.

In the new study, the researchers redesigned filovirus glycoproteins so they stay fixed in their pre-fusion form the shape the immune system needs to recognize and bolster a response against. These redesigned proteins were then placed on Zhu's SApNP platform, forming spherical, virus-like particles coated with many copies of the viral antigens. Biochemical and structural tests confirmed the particles assembled correctly and displayed the proteins as intended.

When tested in mice, these nanoparticle vaccines produced strong immune responses, including antibodies that could both recognize and neutralize several different filoviruses. Additional changes to the sugars on the protein surface further exposed conserved weak points, suggesting that this approach could eventually support a broader, possibly universal vaccine for this dangerous family of viruses.

Building on these results, Zhu's team is extending this structure-guided, nanoparticle-based strategy to other high-risk pathogens, including Lassa virus and Nipah virus. They are also studying new methods to weaken or bypass the mucin shield, allowing the immune system even greater access to critical viral targets.

Many factors affect how the immune system sees a virus and mounts a response, Zhu adds. Locking the antigen into its pre-fusion form gets you maybe 60% of the way there. But many viruses including HIV and filoviruses are covered by a dense glycan shield. If the immune system can't see through that shield, even the best-designed vaccine won't achieve full protection. Overcoming that invisibility cloak' is one of our next big goals.

In addition to Zhu, authors of the study, Rational design of next-generation filovirus vaccines combining glycoprotein stabilization and nanoparticle display with glycan modification, include Yi-Zong Lee, Yi-Nan Zhang, Garrett Ward, Sarah Auclair, Connor DesRoberts, Andrew Ward, Robyn Stanfield, Linling He and Ian Wilson of Scripps Research; Maddy Newby, Joel Allen and Max Crispin of the University of S

LINK:	https://www.scripps.edu/news-and-events/press-room/2025/20251218-zhufi...
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