New nanoparticle vaccines show promise against several deadly filoviruses

New nanoparticle vaccines show promise against several deadly filoviruses

Filoviruses get their name from the Latin word “filum,” meaning “thread,” a reference to their long, thread-like shape. This family of viruses contains some of the most dangerous pathogens known to science, including Ebola, Sudan, Bundibugyo and Marburg viruses. One reason these viruses are still so deadly is the instability of their surface proteins, which makes it difficult for our immune systems to recognize them and difficult for researchers to combat them with treatments or vaccines.

Well, aNature communicationPublished on December 12, 2025, the study (currently a published article) by Scripps Research scientists describes new vaccine candidates designed to protect against multiple strains of filovirus. 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 to several filoviruses, showing a promising path to broader, more effective protection for this dangerous family of viruses.

Filoviruses require better solutions – the outbreaks have been devastating and resulted in extremely high mortality rates. Over the last decade, I have applied 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 ready-to-use strategy.”

Jiang Zhu, senior author, professor in the Department of Integrative Structural and Computational Biology, Scripps Research

Zhu's next-generation vaccine effort focuses on viral surface glycoproteins - the proteins that viruses use to enter cells and that the immune system must target for protection. His team uses an approach called “rational, structure-based design” that examines these glycoproteins in minute detail, constructing stable, well-formed versions and transporting them on virus-shaped protein spheres – 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 big challenge.

Filoviruses such as Ebola virus (EBOV) and Marburg virus (MARV) can cause viral hemorrhagic fever with a fatality rate of up to 90%. During the 2013-2016 Ebola epidemic in West Africa, more than 11,000 people died and over 28,000 were infected. Although two vaccines have been approved against Ebola, no vaccine provides comprehensive protection against the entire filovirus family.

This is due in part to the surface glycoproteins of the filovirus. These proteins are inherently 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 protection makes it more difficult for immune cells to recognize the virus. Once the virus fuses with a cell, the glycoprotein folds back into a post-fusion form, further complicating immune defense.

In 2021, Zhu's team addressed this issue in a study published inNature communicationwhere they mapped the structure of the Ebola glycoprotein 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 recognize and capable of generating stronger, more useful antibody responses.

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

In the new study, researchers redesigned filovirus glycoproteins so that they remain fixed in their pre-fusion shape - the shape the immune system needs to recognize and mount a response against it. These redesigned proteins were then placed onto Zhu's SAPNP platform, forming spherical, virus-like particles coated with many copies of the viral antigens. Biochemical and structural tests confirmed that the particles were assembled correctly and the proteins appeared 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 revealed additional conserved vulnerabilities, suggesting that this approach could ultimately support a more comprehensive, potentially universal vaccine against this dangerous family of viruses.

Building on these results, Zhu's team is expanding this structure-driven, nanoparticle-based strategy to other high-risk pathogens, including Lassa virus and Nipah virus. They are also researching new methods to weaken or circumvent the mucin protective shield to give the immune system even better access to critical viral targets.

“Many factors influence how the immune system recognizes a virus and mounts a response,” Zhu adds. "Capturing the antigen in its prefusion form may get you 60% of the way there. But many viruses - including HIV and filoviruses - are surrounded by a dense glycan shield. If the immune system cannot see through this protection, even the best-designed vaccine will not provide complete protection. Overcoming this 'cloak of invisibility' 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 imaging 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 from the University of Southampton; and Keegan Braz Gomes of Uvax Bio.

The study was supported by Uvax Bio, LLC and the National Institutes of Health. Uvax Bio, a spinoff vaccine company from Scripps Research, uses proprietary platform technology invented in Zhu's lab to develop and commercialize prophylactic vaccines against various infectious diseases.

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