Researchers at Fred Hutch Cancer Center have made significant progress in efforts to stop Epstein-Barr virus (EBV). EBV is a widespread infectious disease that affects approximately 95% of people worldwide and is associated with several cancers, neurodegenerative diseases, and other long-term diseases.
Using mice engineered to produce human antibodies, the researchers created a new monoclonal antibody designed to block the virus from attaching to and entering human immune cells. The findings, published in Cell Reports Medicine, show that one of these antibodies was able to completely prevent infection in mice, which have immune systems similar to humans, when exposed to EBV.
“Finding human antibodies that block Epstein-Barr virus from infecting our immune cells has been particularly difficult because, unlike other viruses, EBV has found a way to bind to almost all B cells,” explained Dr. Andrew McGuire, a biochemist and cell biologist in Fred Hutch’s Vaccines and Infectious Diseases division. “We decided to use new technology to fill this knowledge gap and were finally able to take an important step towards blocking one of the world’s most common viruses.”
Novel antibody strategies targeting EBV entry points
A major hurdle in developing these treatments is identifying antibodies that can block EBV without triggering an immune response to the treatment itself, which often occurs when antibodies are derived from non-human sources. To address this, the researchers focused on two viral proteins: gp350 and gp42. The gp350 protein helps the virus attach to human cells, while gp42 allows the virus to fuse with and enter those cells.
Using a specialized mouse model, researchers identified two monoclonal antibodies that target gp350 and eight monoclonal antibodies that target gp42.
“We not only identified important antibodies against the Epstein-Barr virus, but we also validated an innovative new approach to discovering protective antibodies against other pathogens,” said Crystal Chan, a pathology doctoral student in the McGuire lab. “As a budding scientist, this was an exciting discovery and helped me understand how science often leads to unexpected discoveries.”
Further analysis, supported by Fred Hutch’s Antibody Technology Core, revealed specific weaknesses in the virus that could guide future vaccine design. In final testing, one antibody targeting gp42 completely blocked EBV infection, while the antibody targeting gp350 provided partial protection.
Potential impact on high-risk transplant patients
Each year, more than 128,000 people in the United States undergo solid organ or bone marrow transplants. These patients often require immunosuppressants, which may allow EBV to reactivate or spread unchecked. Currently, there are no targeted therapies to prevent this.
Posttransplant lymphoproliferative disorder (PTLD) is a serious and sometimes life-threatening form of lymphoma that can develop after transplantation and is most often caused by uncontrolled EBV infection.
“Post-transplant lymphoproliferative disease (PTLD), mostly EBV-related lymphoma, is a frequent cause of morbidity and mortality after organ transplantation,” notes Rachel Bender Ignacio, MD, MPH, associate professor of infectious diseases at Fred Hutch and the University of Washington School of Medicine. “Prevention of EBV viremia has strong potential to reduce the incidence of PTLD and limit the need for immunosuppression, thereby helping to preserve graft function while improving overall patient outcomes. Effective prevention of EBV viremia remains a critical unmet need in transplant medicine.”
Patients can be exposed to EBV through donor organs that harbor latent virus. In people who have been previously infected, immunosuppression may allow the virus to reactivate and multiply. Children undergoing transplantation may be particularly vulnerable because many have not yet been exposed to EBV.
Towards preventive antibody therapy
The research team envisions a future where these monoclonal antibodies can be administered as an intravenous drip to prevent EBV infection and reactivation, especially in high-risk groups. Such treatments may help prevent PTLD and other complications by blocking the virus early.
Fred Hutch has filed intellectual property claims related to antibodies discovered in the study. McGuire and Chan are currently working with collaborators and industry partners to move the research closer to clinical use. Next steps could include safety studies in healthy adults, followed by clinical trials in the highest-risk patients.
“There is momentum to advance our discoveries into treatments that can make a huge difference for patients receiving transplants,” McGuire said. “After years of searching for viable ways to protect ourselves from the Epstein-Barr virus, this is a major advance for the scientific community and those most at risk of complications from this virus.”
