Breakthrough Discovery Targets Virus Infecting 95% of the World’s Population

Scientists have taken a significant step toward neutralizing Epstein-Barr virus.

Scientists at Fred Hutch Cancer Center have reported an important advance in the effort to stop Epstein Barr virus (EBV), a virus believed to infect about 95% of people worldwide. EBV has been linked to several cancers, neurodegenerative disorders, and other long term health conditions.

To tackle the virus, researchers used mice engineered with human antibody genes. This approach allowed them to generate fully human monoclonal antibodies designed to block two critical viral surface proteins. These proteins normally help EBV attach to and enter human immune cells. The findings, published in Cell Reports Medicine, highlight one antibody in particular that protected mice with human immune systems from infection when they were exposed to EBV.

“Finding human antibodies that block Epstein Barr virus from infecting our immune cells has been particularly challenging because, unlike other viruses, EBV finds a way to bind to nearly every one of our B cells,” explained Andrew McGuire, PhD, a biochemist and cellular biologist in the Vaccine and Infectious Disease Division at Fred Hutch. “We decided to use new technologies to try to fill this knowledge gap and we ended up taking a critical step toward blocking one of the world’s most common viruses.”

A new scientific approach yields answers to a puzzling challenge

One of the central obstacles in this research was identifying human monoclonal antibodies that could stop EBV without provoking an anti drug immune response. Such reactions are common when patients receive antibodies originally produced in other animals.

The team concentrated on two viral proteins. The first, gp350, enables EBV to latch onto receptors on human cells. The second, gp42, plays a key role in allowing the virus to fuse with and enter those cells. By using a specialized mouse model containing human antibody genes, the scientists generated two monoclonal antibodies targeting gp350 and eight targeting gp42.

“Not only did we identify important antibodies against Epstein Barr virus, but we also validated an innovative a new approach for discovering protective antibodies against other pathogens,” noted Crystal Chhan, a pathobiology PhD student in the McGuire Lab. “As an early-career scientist, it was an exciting finding and has helped me appreciate how science often leads to unexpected discoveries.”

Additional studies conducted with support from Fred Hutch’s Antibody Tech Core identified specific weak points on the virus that may guide future vaccine design. In laboratory tests, one antibody directed at gp42 completely prevented EBV infection in mice with human immune systems. An antibody against gp350 offered partial protection.

Hope for patients at the highest risk of Epstein Barr virus

Each year, more than 128,000 people in the U.S. receive solid organ or bone marrow transplants. These patients must take medications that suppress their immune systems to prevent rejection. Currently, there are no targeted treatments that reliably prevent EBV infection or reactivation during this vulnerable period.

Uncontrolled EBV infection after transplantation can lead to post-transplant lymphoproliferative disorders (PTLD), an aggressive and sometimes life-threatening lymphoma. PTLD most often develops when EBV spreads unchecked in patients whose immune defenses are weakened.

“Post-transplant lymphoproliferative disorders (PTLD), most of which are EBV-associated lymphomas, are a frequent cause of morbidity and mortality after organ transplantation,” noted Rachel Bender Ignacio, MD, MPH, an associate professor and infectious disease physician at Fred Hutch and University of Washington School of Medicine. “Preventing EBV viremia has strong potential to reduce the incidence of PTLD and limit the need to reduce immunosuppression, thereby helping preserve graft function while improving overall patient outcomes. Effective prevention of EBV viremia remains a significant unmet need in transplant medicine.”

Transplant recipients can acquire EBV if donor organs or cells carry dormant virus. Patients who were previously infected may also experience viral reactivation when immunosuppressive drugs weaken immune control. Children undergoing transplants may face especially high risk because many have not yet been exposed to EBV and therefore lack natural immunity.

The next mile

The researchers are working toward a therapy that would involve infusing these monoclonal antibodies into high risk patients. The goal is to block EBV infection or reactivation and reduce the likelihood of PTLD.

Fred Hutch has filed for intellectual property protection covering the antibodies identified in the study. McGuire and Chhan are collaborating with academic partners and an industry collaborator to move the potential therapy forward. If development continues successfully, the treatment would first undergo safety testing in healthy adult volunteers before advancing to clinical trials in transplant recipients and other immunocompromised patients.

“There’s momentum to advance our discovery to a therapy that would make a huge difference for patients undergoing transplant,” said McGuire. “After many years of searching for a viable way to protect against Epstein Barr virus, this is a significant stride for the scientific community and the people at the highest risk of complications from this virus.”

Reference: “Transgenic mouse-derived human monoclonal antibodies targeting EBV gp350 and gp42 provide basis for therapeutic development” by Crystal B. Chhan, Kevin Lang, Amelia R. Davis, Yu-Hsin Wan, Nicholas T. Aldridge, Gargi Kher, Samuel C. Scharffenberger, Samantha R. Hardy, Roman Iureniev, Natalia V. Giltiay, Kristina R. Edwards, Stefan Radtke, Hans-Peter Kiem, Marie Pancera and Andrew T. McGuire, 17 February 2026, Cell Reports Medicine.
DOI: 10.1016/j.xcrm.2026.102618

Funding: National Institute of Allergy and Infectious Diseases, National Cancer Institute, Fred Hutchinson Cancer Research Center

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