April 10, 2026

Improving vaccine design for Ebola, HIV and more Scripps Research scientists and colleagues develop a nanodisc platform that offers a clearer view of how key viral proteins interact with antibodies.

April 10, 2026

LA JOLLA, CA Viruses are masters at invading our cells thanks to specialized proteins that coat their surfaces. When scientists design vaccines, they often create versions of these viral surface proteins to study how our immune systems might respond. But those lab-made proteins typically lack key parts that sit within the virus' membrane, so they don't always behave the way they would on a real virus. This has made it difficult to understand how antibodies actually identify and neutralize these viral targets.

Now, scientists at Scripps Research, in collaboration with IAVI and other institutes, have created a platform that allows viral surface proteins to be studied in a form that more closely resembles how they appear naturally. The new approach utilizes nanodisc technology where these proteins are embedded into particles made of lipid molecules, preserving them in a membrane-like structure. This could help guide vaccine research by better revealing how antibodies and viral proteins interact.

Outlined in Nature Communications on February 10, 2026, the platform was tested using proteins from HIV and Ebola: two viruses that have long challenged vaccine developers because their surface proteins are difficult for the immune system to target effectively. However, the approach could be applied broadly to other viruses with similar membrane-embedded proteins, such as influenza and SARS-CoV-2.

For many years, we've had to rely on versions of viral proteins that are missing important pieces, says co-senior author William Schief, a professor at Scripps Research and executive director of vaccine design at IAVI's Neutralizing Antibody Center. Our platform lets us study these proteins in a setting that better reflects their natural environment, which is critical if we want to understand how protective antibodies recognize a virus.

In real viruses, surface proteins aren't free-floating, but rather embedded in a lipid membrane and arranged in specific shapes. Yet most lab studies remove the membrane-anchoring region to make the proteins easier to produce and analyze. While useful, those shortcuts can obscure important features, particularly for antibodies that target regions near the base of the protein, close to the viral membrane.

To address this, the research team assembled vaccine candidate viral proteins into nanodiscs, which are small and stable patches of membrane that hold the proteins in place. These lipid discs mimic the virus' outer layer, helping preserve how antibodies would identify proteins in an actual virus. Their novel platform allowed the researchers to use a range of standard vaccine-development tools, including tests of antibody binding, sorting of immune cells and high-resolution imaging.

Putting all of these components together into a single, reliable system was the key, says first author Kimmo Rantalainen, a senior scientist in Schief's lab. The individual pieces already existed, but making them work together in a way that's reproducible and scalable opens up new possibilities for how vaccines are analyzed and designed.

Using HIV as a test case, the team focused on a conserved region of the virus' surface protein that sits near the membrane. This region is targeted by a class of antibodies capable of blocking nearly all HIV variants. Such antibodies recognize viral parts that remain similar even as they mutate an immune response scientists hope vaccines could eventually trigger.

With their nanodisc platform, the researchers were able to capture detailed structural snapshots of how these antibodies interact with the viral protein in its membrane context, revealing features that aren't visible when the protein is studied on its own. Those insights also help explain how certain antibodies may neutralize a virus by destabilizing the protein structures it uses to infect cells, offering clues for how future vaccines might better engage similar immune responses.

The structure gave us a level of detail we simply couldn't access before, notes Rantalainen. It showed us new interactions at the membrane interface and suggested why those matter for antibody function.

To demonstrate that the approach isn't limited to HIV, the team also applied their nanodisc platform to Ebola proteins, confirming that antibodies could identify and bind to these proteins in the same membrane-like environment.

Beyond structural studies, this platform can be used to analyze immune responses to vaccine candidates. By using the nanodiscs as molecular bait, researchers can isolate and study cells that recognize viral proteins, providing a clearer picture of how the body responds to a given vaccine candidate. And because the system is scalable, what once took a month or longer to prepare can now be done in about a week, making it practical for comparing multiple candidate designs side by side.

Although the platform isn't a vaccine itself, scientists can use it as a tool to inform and accelerate vaccine research, particularly for viruses where traditional approaches have fallen short.

This gives the field a more realistic, accurate way to test ideas early on, emphasizes Schief. By improving how we study viral proteins and antibody responses, we hope this platform will help advance next-generation vaccines against some of the world's most challenging viruses.

In addition to Schief and Rantalainen, authors of the study Virus glycoprotein nanodisc platform for vaccine analytics, include Alessia Liguori, Gabriel Ozorowski, Claudia Flynn, Jon M. Steichen, Olivia M. Swanson, Patrick J. Madden, Sabyasachi Baboo, Swastik Phule

LINK:	https://www.scripps.edu/news-and-events/press-room/2026/20260410-ranta...
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