Viruses are very good at getting inside our cells because they wear special proteins on their outer shells. These proteins are the main targets for vaccines. To learn how they work, scientists often make simplified copies in the lab. But those copies usually miss parts that sit inside the virus’s outer layer, so they don’t act exactly like the real thing.
A team at Scripps Research, together with IAVI and other partners, created a new way to study these proteins in a more natural form. They use nanodiscs – tiny, round pieces of fat (lipid) that act like a mini‑membrane. By placing the viral proteins into these nanodiscs, the proteins keep their true shape and behavior.
Nanodiscs Act Like Real Virus Membranes
The method was tested with proteins from HIV and Ebola, two viruses that have been hard to target with vaccines. The researchers say the same approach could work for other viruses such as flu and COVID‑19.
In a real virus, surface proteins sit in a fatty membrane and are arranged in specific patterns. Lab studies often cut off the membrane‑anchoring part to make the proteins easier to handle. This shortcut can hide important details, especially the parts near the membrane that many antibodies aim for.
By embedding the proteins in nanodiscs, scientists can see how antibodies bind to them in a setting that looks a lot like a true virus. The system works with common vaccine‑research tools like binding tests, cell sorting and high‑resolution imaging.
New Clues About Antibody Actions
Using HIV as an example, the team focused on a stable region of the virus’s outer protein that sits close to the membrane. This spot is attacked by a group of antibodies that can block many different HIV strains. Those antibodies recognize parts of the virus that stay the same even when the virus mutates.
The nanodisc platform let the researchers capture detailed pictures of how these antibodies grip the protein in its natural membrane setting. They saw features that are invisible when the protein is studied alone. The images suggest that some antibodies may stop the virus by breaking apart the structures it uses to enter cells, a useful hint for designing stronger vaccines.
"The structure gave us a level of detail we simply couldn't access before," said researcher Rantalainen. "It showed new interactions at the membrane and why they matter for antibody function."
Works for More Than HIV
The scientists also tried the technique with Ebola proteins. The results showed that antibodies could still find and bind to the proteins inside the nanodisc, confirming the method works for different viruses.
Beyond looking at structures, the nanodiscs can act as molecular “bait” to pull out immune cells that react to a specific viral protein. This helps researchers understand how the body responds to various vaccine candidates. The whole process, which used to take a month or more, can now be finished in about a week, making it easier to compare many designs.
A Helpful Tool for Faster Vaccine Development
While nanodiscs are not a vaccine themselves, they give scientists a more realistic way to test ideas early on. By improving the study of viral proteins and antibody responses, the platform could speed up the creation of next‑generation vaccines against some of the toughest viruses.
"This gives the field a more realistic, accurate way to test ideas early on," said Schief. "We hope it will help bring better vaccines to the world sooner."