Researchers have developed monoclonal antibodies that completely prevent Epstein-Barr virus (EBV) from infecting human immune cells, according to a study published in Cell Reports Medicine on March 27, 2025.
The research, a collaboration between the Fred Hutch Cancer Center and the University of Washington, identified antibodies targeting two key viral surface proteins, marking a significant step toward blocking one of the world's most common viruses.
Research Method
The study focused on two proteins on the surface of the Epstein-Barr virus:
- gp350: Facilitates the virus's attachment to human cells.
- gp42: Enables the virus to fuse with and enter those cells.
To reduce the risk of immune reactions against non-human therapies, the team used mice genetically engineered to produce human antibodies. From this approach, they isolated ten new monoclonal antibodies: two targeting gp350 and eight targeting gp42.
Preclinical Results
In experiments using mice with human-like immune systems, the results were striking:
- One antibody targeting the gp42 protein completely prevented EBV infection.
- A separate antibody targeting the gp350 protein provided partial protection.
Further analysis by Fred Hutch's Antibody Tech Core identified specific sites of vulnerability on the virus, which could inform future vaccine design.
"Finding human antibodies to block EBV infection has been challenging because EBV binds to nearly all B cells," said Andrew McGuire, PhD, a biochemist and cellular biologist at Fred Hutch.
Background on Epstein-Barr Virus
Epstein-Barr virus is estimated to infect approximately 95% of the global population and remains in the body for life. The virus is associated with:
- Several cancers
- Neurodegenerative conditions, including multiple sclerosis
- Other long-term illnesses
Developing human antibodies that effectively block EBV has been difficult because the virus binds to nearly all B cells.
Potential Applications
The research team envisions these antibodies could be administered as an infusion to prevent EBV infection or reactivation in high-risk populations.
More than 128,000 people in the United States undergo solid organ or bone marrow transplants annually.
Transplant patients are considered a high-risk group because immunosuppressive drugs taken to prevent organ rejection can allow latent EBV to reactivate or spread unchecked.
Post-transplant lymphoproliferative disorders (PTLD), most of which are EBV-associated lymphomas, are described by researchers as a significant cause of morbidity and mortality after organ transplantation. There are currently no specific targeted therapies to prevent EBV reactivation in transplant patients. Children undergoing immunosuppression for transplant may be particularly vulnerable, as a higher proportion have not yet been exposed to EBV.
"Preventing EBV viremia could reduce the incidence of PTLD and limit the need to reduce immunosuppression, potentially helping preserve graft function," said Rachel Bender Ignacio, MD, MPH, an associate professor at Fred Hutch and the University of Washington School of Medicine.
Next Steps
Fred Hutch has filed intellectual property claims for the identified monoclonal antibodies. Researchers are working with collaborators and an industry partner to advance the research toward clinical use.
Potential next steps include:
- Safety testing in healthy adult volunteers
- Clinical trials in high-risk patient populations
Crystal Chhan, a pathobiology PhD student in the McGuire Lab, stated that the research validated a new approach for discovering protective antibodies against other pathogens.