New Nanodisc Tech Reveals How Antibodies Really Attack Viruses

Scientists have developed a nanodisc technology that allows viral proteins to be examined in a setting closely resembling their natural membrane environment, providing clearer understanding of how antibodies recognize viruses.

Nanodisc Technology Enhances Viral Protein Analysis

Viruses infect human cells effectively due to specialized proteins on their surfaces, which are critical targets for vaccines. Traditional laboratory studies often use simplified versions of these proteins that lack membrane-embedded sections, limiting the ability to observe their authentic behavior. Researchers at Scripps Research, collaborating with IAVI and other partners, introduced a platform that incorporates viral proteins into lipid-based nanodiscs. This approach preserves the proteins’ natural structure and function, enabling more accurate analysis of antibody interactions.

The platform was tested on proteins from HIV and Ebola viruses, which have historically been challenging for vaccine design due to their elusive surface proteins. The researchers note that this method could also apply to other viruses with membrane-bound proteins, such as influenza and SARS-CoV-2.

Importance of Membrane Context in Antibody Recognition

In real viruses, surface proteins are anchored within lipid membranes and arranged in specific conformations. Many lab studies remove the membrane-anchoring parts to simplify experiments, which can obscure critical details, especially for antibodies targeting regions near the protein base close to the membrane. To address this, the team embedded vaccine candidate proteins into nanodiscs—small, stable lipid sections that mimic a virus’s outer layer—maintaining natural antibody recognition.

This system supports various standard vaccine development techniques, including antibody binding assays, immune cell isolation, and high-resolution imaging. First author Kimmo Rantalainen explained that integrating these components into a reproducible and scalable system expands possibilities for vaccine analysis and design.

Detailed Insights From HIV Antibody Studies

Focusing on HIV, the researchers examined a conserved region of the virus’s surface protein near the membrane, targeted by antibodies capable of neutralizing diverse HIV variants. These antibodies recognize relatively stable viral regions despite mutations, making them valuable for vaccine strategies. Using the nanodisc platform, the team obtained detailed structural images revealing interactions at the membrane interface that were previously inaccessible. The findings suggest mechanisms by which antibodies neutralize viruses by disrupting essential viral structures.

Rantalainen noted that the structural data provided unprecedented detail about antibody function related to the membrane environment.

Extending the Platform to Other Viruses

The researchers also applied the nanodisc system to Ebola virus proteins, demonstrating that antibodies could recognize and bind these proteins within the membrane-like environment. This confirmed the platform’s applicability beyond a single virus.

Accelerating Immune Response Studies

Beyond structural analysis, the platform facilitates studying immune responses to vaccine candidates. The nanodiscs serve as molecular bait to isolate immune cells recognizing viral proteins, offering clearer insights into immune reactions. The system accelerates processes that previously took a month or more, reducing them to about a week and enabling more efficient comparison of vaccine candidates.

Advancing Future Vaccine Development

Although not a vaccine itself, this platform provides a valuable tool to improve vaccine development, particularly for viruses that have been difficult to target with traditional methods. William Schief, co-senior author and executive director of vaccine design at IAVI’s Neutralizing Antibody Center, emphasized that this approach offers a more realistic way to evaluate viral proteins and antibody responses early in the development process, potentially aiding next-generation vaccine advancement.

The study, titled “Virus glycoprotein nanodisc platform for vaccine analytics,” was published on 10 February 2026 in Nature Communications. Authors include Kimmo Rantalainen, Alessia Liguori, Gabriel Ozorowski, Claudia Flynn, Jon M. Steichen, Olivia M. Swanson, Patrick J. Madden, Sabyasachi Baboo, Swastik Phulera, Anant Gharpure, Danny Lu, Oleksandr Kalyuzhniy, Patrick Skog, Sierra Terada, Monolina Shil, Jolene K. Diedrich, Erik Georgeson, Ryan Tingle, Saman Eskandarzadeh, Wen-Hsin Lee, Nushin Alavi, Diana Goodwin, Michael Kubitz, Sonya Amirzehni, Devin Sok, Jeong Hyun Lee, John R. Yates III, James C. Paulson, Shane Crotty, Torben Schiffner, Andrew B. Ward of Scripps Research, and Sunny Himansu of Moderna Inc.

This research received funding from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (grants UM1 AI144462, R01 AI147826, R56 AI192143, and 5F31AI179426-02); the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (grants INV-007522, INV-008813, and INV-002916); the IAVI Neutralizing Antibody Center (INV-034657 and INV-064772); and the Alexander von Humboldt Foundation.