Fred Hutch Scientists Identify Human Antibodies That Block Epstein-Barr Virus in Mice

Epstein-Barr virus infects roughly 95 percent of the global adult population. For most people, the infection occurs in adolescence or young adulthood, causes mononucleosis or no symptoms at all, and then persists silently in B cells for life. The immune system holds it in check. That equilibrium holds - until the immune system is deliberately suppressed.

Organ and bone marrow transplantation requires immunosuppression to prevent rejection. For the more than 128,000 Americans who undergo solid organ or bone marrow transplant annually, that suppression creates a window during which latent EBV can replicate unchecked. The result can be post-transplant lymphoproliferative disorder (PTLD) - an aggressive lymphoma that develops in a substantial fraction of EBV-positive transplant recipients and carries significant mortality risk. Currently, no specific therapy exists to prevent EBV from reactivating or causing PTLD in these patients.

A study published February 17, 2026 in Cell Reports Medicine by researchers at Fred Hutchinson Cancer Center describes a meaningful step toward filling that gap.

Why EBV Is Hard to Block

Developing protective antibodies against EBV has posed a specific challenge. The virus uses two surface antigens in sequence to infect human B cells: gp350, which binds to the complement receptor CD21 found on nearly all B cells, and gp42, which facilitates membrane fusion and viral entry. Because CD21 is expressed on virtually every B cell in the body, EBV can infect an extremely broad cellular target. Blocking both binding and entry requires antibodies that address two distinct steps in the viral entry process.

An additional challenge is immunogenicity. Antibodies raised in other animals often trigger immune responses in human patients when used therapeutically. Generating genuinely human antibodies requires either deriving them from human donors or using animals engineered to produce human antibody sequences.

The Humanized Mouse Strategy

Andrew McGuire, PhD, a biochemist in the Vaccine and Infectious Disease Division at Fred Hutch, and his team used a mouse model carrying human antibody genes - a platform that generates antibodies with human protein sequences, avoiding the anti-drug response problem. The mice were immunized against EBV antigens, and their antibody responses were screened for candidates targeting gp350 and gp42.

The effort yielded two monoclonal antibodies against gp350 and eight against gp42. Further analysis at Fred Hutch's Antibody Tech Core identified sites of vulnerability on both antigens that could inform future vaccine design. In the study's final stage, the researchers challenged mice engineered to carry human immune systems with EBV. One of the monoclonal antibodies against gp42 completely prevented infection. A monoclonal antibody against gp350 provided partial protection.

The Target Patient Population

Rachel Bender Ignacio, MD, MPH, an associate professor and infectious disease physician at Fred Hutch and the University of Washington School of Medicine, described the clinical need: "Post-transplant lymphoproliferative disorders, most of which are EBV-associated lymphomas, are a frequent cause of morbidity and mortality after organ transplantation. 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."

Children undergoing transplant are particularly at risk, because a higher proportion of pediatric transplant recipients have not yet been exposed to EBV. For an EBV-naive child receiving an organ from an EBV-positive donor, the combination of primary infection and immunosuppression creates an especially dangerous situation.

Next Steps and Limits

Fred Hutch has filed for intellectual property rights covering the identified monoclonal antibodies. McGuire and colleagues are working with scientific collaborators and an industry partner to advance toward clinical development. The envisioned pathway follows a standard preclinical-to-clinical trajectory: safety testing in healthy adult volunteers, followed by trials in the target immunocompromised population if safety is acceptable.

The mouse infection data represent an early proof of concept. Mice with humanized immune systems are useful models but differ from human transplant patients in important ways - the degree of immunosuppression, the baseline immune history, and the nature of the B cell populations involved. Whether antibody levels achievable with therapeutic dosing in humans will be sufficient to prevent EBV viremia under clinical immunosuppression requires testing in human trials. The timeline from current stage to a clinically available therapy is measured in years, not months.