Filovirus Detection by Immune System Improved by Nanoparticle Vaccine

Filoviruses, such as Ebola virus and Marburg virus, can cause viral hemorrhagic fever, with fatality rates reaching up to 90%. While two vaccines are approved for Ebola, no vaccine provides broad protection across the full filovirus family. The instability of filovirus surface proteins offers a challenge for immune system detection. 

In a new study published in Nature Communications titled, “Rational design of next-generation filovirus vaccines combining glycoprotein stabilization and nanoparticle display with glycan modification,” researchers from Scripps Research describe new vaccines that display filovirus surface proteins on engineered, self-assembling protein nanoparticles (SApNPs) to improve immune system detection of the virus.  

The vaccine platform was previously applied to viruses such as HIV-1, hepatitis C, RSV, hMPV, and influenza—with filoviruses providing the next challenge. In a mouse model, the nanoparticles triggered strong antibody responses across several filoviruses, highlighting a promising path toward viral protection. 

“Filoviruses demand better solutions—outbreaks have been devastating, with extremely high mortality rates,” said Jiang Zhu, PhD, corresponding author and professor in the Department of Integrative Structural and Computational Biology at Scripps. “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.” 

The study applied a rational design strategy for stabilizing glycoproteins (GP) in a range of filoviruses. X-ray crystallography results showed atomic-level details of the redesigned Ebola virus GP. Cryo-electron microscopy revealed how a pan-orthoebolavirus neutralizing antibody targets a conserved site on the stabilized Sudan virus GP, along with a low-resolution model of antibody-bound Ravn virus.   

In 2021, Zhu’s team made the initial step in glycoprotein stabilization by mapping the Ebola glycoprotein structure in detail. By removing the mucin-rich segments, the authors generated a more accessible version of the protein that was easier for the immune system to detect.

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. In addition, the authors are investigating 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,” said Zhu “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.”