International AIDS Vaccine Initiative, Inc.

A new nanodisc-based platform lets scientists study viral proteins in a form that closely mimics real viruses, revealing how antibodies truly recognize them. This approach uncovered hidden interactions in viruses like HIV and Ebola that traditional methods missed. By recreating the virus’s membrane environment, researchers can better understand how immune defenses work. The technique could speed up the development of more effective vaccines.Viruses are highly effective at entering human cells, largely because of specialized proteins that cover their outer surfaces. These proteins are key targets in vaccine development. To study them, scientists typically create lab versions to see how the immune system might respond. However, these simplified versions often leave out important sections that normally sit within the virus's outer membrane. As a result, they do not always behave the same way they would in a real infection, making it harder to understand how antibodies truly recognize and stop viruses. Researchers at Scripps Research, working with IAVI and other collaborators, have now developed a new platform that allows these viral proteins to be studied in a much more natural form. Their method uses nanodisc technology, which places the proteins into tiny particles made of lipids. This setup mimics the virus's outer membrane, helping preserve the proteins' natural structure and behavior. The approach offers a clearer view of how antibodies interact with viruses and could help guide future vaccine design. Nanodisc Technology Mimics Viral Membranes The study, published in Nature Communications, tested the platform using proteins from HIV and Ebola. These viruses have long posed challenges for vaccine development because their surface proteins are especially difficult for the immune system to target. The researchers believe the same method could also be applied to other viruses with similar membrane-bound proteins, including 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 are embedded within a lipid membrane and arranged in specific shapes. In contrast, most laboratory studies remove the membrane-anchoring portion to make the proteins easier to handle. While this simplifies experiments, it can hide important details, especially for antibodies that target regions near the base of the protein close to the membrane. To overcome this limitation, the team incorporated vaccine candidate proteins into nanodiscs. These small, stable lipid patches hold the proteins in place and closely resemble the virus's outer layer. This setup allows scientists to study how antibodies interact with proteins in a more realistic context. The platform also supports standard vaccine research tools, including antibody binding tests, immune cell sorting 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." New Insights Into Antibody Responses Using HIV as an example, the researchers focused on a stable region of the virus's surface protein located near the membrane. This region is targeted by a group of antibodies that can block a wide range of HIV variants. These antibodies recognize parts of the virus that remain consistent even as it mutates, making them especially valuable for vaccine research. With the nanodisc platform, the team captured detailed structural views of how these antibodies interact with viral proteins in their natural membrane environment. This revealed features that cannot be seen when proteins are studied in isolation. The findings also shed light on how certain antibodies may neutralize viruses by disrupting the structures they use to infect cells, offering useful clues for designing better vaccines. "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." Applications Beyond HIV and Ebola To show that the method is broadly useful, the researchers also applied it to Ebola proteins. The results confirmed that antibodies could successfully recognize and bind to these proteins within the same membrane-like environment. The platform is not limited to structural analysis. It can also be used to study immune responses to vaccine candidates. By using nanodiscs as molecular "bait," scientists can isolate immune cells that respond to specific viral proteins. This provides a clearer understanding of how the body reacts to different vaccine designs. In addition, the system is efficient. Processes that once took a month or more can now be completed in about a week, making it easier to compare multiple vaccine candidates. A Tool to Accelerate Vaccine Development While the platform itself is not a vaccine, it serves as a powerful tool to support vaccine research. This is especially important for viruses that have been difficult to target using traditional methods. "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 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 and Andrew B. Ward of Scripps Research; and Sunny Himansu of Moderna Inc. This work was supported by 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.

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 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 and Andrew B. Ward of Scripps Research; and Sunny Himansu of Moderna Inc. This work was supported by 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. For more information, contact press@scripps.edu See More News

Led by a team of African researchers, first doses of the novel T cell-inducing GRAdHIVNE1 vaccine candidate have been given. HARARE, Zimbabwe; ROME, Italy; NEW YORK, NY, and CAMBRIDGE, MA, USA I August 4, 2025 I The Mutala Trust, ReiThera Srl (ReiThera), the Ragon Institute of Mass General Brigham, MIT, and Harvard (the Ragon Institute), and IAVI are pleased to announce that the first doses of an investigational HIV vaccine candidate have been administered. The vaccine candidate, Gorilla Adenovirus Vectored HIV Networked Epitopes Vaccine (GRAdHIVNE1), was first administered on July 28, 2025, at the Mutala Trust clinical trial site in Harare, Zimbabwe. This effort is made possible by a global collaboration and a team of African principal investigators who will lead the clinical research in South Africa and Zimbabwe (listed below). Vaccine immunogenicity will also be assessed locally by a network of state-of-the-art African research institutes: Cape Town HVTN Immunology Laboratory in Cape Town, African Health Research Institute in Durban, and the National Institute for Communicable Diseases in Johannesburg, South Africa. This Phase 1, first-in-human clinical trial will enroll approximately 120 healthy adults aged 18–50 years, including 48 people living with HIV who are virally suppressed on antiretroviral therapy (ART). The trial is designed to assess the safety and immunogenicity of the vaccine candidate in people living with and without HIV. Participants will receive either one or two doses of the investigational vaccine or a placebo and will be monitored over a period of 19 months for safety and immune responses. This clinical trial, IAVI C114, is sponsored by IAVI. GRAdHIVNE1 has been made possible by a collaborative effort. ReiThera developed the GRAd viral vector platform and manufactured the vaccine candidate, while the Ragon Institute designed the immunogen using novel strategies to identify protective HIV epitopes and facilitate their targeting by T cells. This clinical program is funded by the Gates Foundation. The IAVI C114 clinical trial is taking place at three clinical trial sites: the Mutala Trust Clinical Trial Site, in Harare, Zimbabwe; the Desmond Tutu Health Foundation (DTHF), in Cape Town, South Africa; and the Africa Health Research Institute (AHRI), in Durban, South Africa. To determine the vaccine candidate’s potential for relevance in sub-Saharan Africa, where disease burden is greatest, it is essential that the candidate be tested within communities affected by the epidemic. “This is a landmark moment for South Africa, Zimbabwe, and the continent. It shows the power of true partnership: IAVI’s sponsorship, ReiThera’s GRAd technology, the Ragon Institute’s innovative immunogen built on decades of science, and African investigators co-leading every phase of the trial. We are edging closer to an HIV vaccine, made possible by global collaboration, with clinical trials conducted in Africa, for Africa, and for the world.” said Dr. Tariro Makadzange, clinical trial lead, Mutala Trust. “This trial represents the future of vaccine development, rooted in Africa, built through global partnerships, and designed for the communities most affected by HIV,” said Dr. Vincent Muturi-Kioi, HIV vaccines product development team lead at IAVI. The vaccine candidate is designed to engage the immune system to recognize and target critical structural regions of HIV using a clinically validated, potent, T cell-inducing GRAd vector. This approach will be evaluated to assess the ability of the vaccine candidate to direct strong CD8+ T cell immune responses towards these vulnerable viral regions. “We are thrilled to be moving insights from our long-term studies of spontaneous elite controllers of HIV toward the development of GRAdHIVNE1 and its testing in Africa. We are truly grateful to the network of global and African partners that have come together to make the IAVI C114 trial a reality,” said Dr. Gaurav Gaiha, associate professor of medicine at Harvard Medical School and principal investigator at the Ragon Institute of Mass General Brigham, MIT, and Harvard. Because CD8+ T cells induced by this vaccine hold promise for targeting HIV-infected cells, this clinical trial will also assess the safety and immune response in people living with HIV. These data will be used to assess the suitability of the vaccine candidate for the development of investigational HIV therapeutic and curative interventions. “We are enormously pleased with the launch of this Phase 1 trial representing the result of a successful global partnership,” said Stefano Colloca, CEO and co-founder of ReiThera. “This candidate HIV vaccine, built on our GRAd platform, holds great promise to trigger a strong CD8 response targeting vulnerable viral regions.” Principal investigators leading clinical trial sites: About IAVI IAVI is a global nonprofit scientific organization that works to develop vaccines and antibodies to prevent HIV and other infectious diseases, with a focus on innovation and equitable access. IAVI is the sponsor of this trial. Read more at www.iavi.org . About Mutala Trust Mutala Trust is founding member of Africa Clinical Research Network (ACRN) and is a site based in Harare, Zimbabwe. It is known for conducting high-quality, ethically sound clinical trials addressing diseases that affect African communities. Mutala is the clinical lead site for the study. About ReiThera Srl. ReiThera Srl, an Italian CDMO specializing in technology and process development as well as GMP manufacturing of viral vectors for genetic vaccines and advanced therapies, is the developer and owner of the GRAd platform used for this HIV vaccine. About the Ragon Institute of Mass General Brigham, MIT, and Harvard The Ragon Institute of Mass General Brigham, MIT, and Harvard was established with a collaborative scientific mission among these institutions that brings scientists, clinicians and engineers together to harness the immune system to combat and cure human disease. They contributed to vaccine design. For more information, visit www.ragoninstitute.org SOURCE: ReiThera