Scientists Develop Antibodies That Block the Virus Infecting 95% of Humanity — and Its Links to Cancer

Researchers at Fred Hutchinson Cancer Center in Seattle have developed a monoclonal antibody that protects bone marrow and organ transplant patients from Epstein-Barr virus reactivation, one of the most serious infectious complications that arise when patients are placed on immunosuppressive therapy following transplantation. The antibody, described in a paper published Wednesday in the New England Journal of Medicine, neutralizes the virus before it can establish new infections in B cells and demonstrated 87 percent efficacy at preventing EBV-related complications in a phase 2 clinical trial involving 340 transplant patients across 14 centers in the United States and Canada.

Epstein-Barr virus infects more than 90 percent of adults worldwide and persists for life in a latent state within B lymphocytes, the immune cells responsible for producing antibodies. Under normal immune conditions, the virus remains quiescent, held in check by cytotoxic T cells that recognize and kill B cells showing signs of viral reactivation. But in transplant patients, who receive powerful immunosuppressive drugs to prevent graft rejection, T cell surveillance is severely impaired. Without this surveillance, EBV can reactivate aggressively, driving B cell proliferation that in severe cases progresses to post-transplant lymphoproliferative disease, a form of lymphoma that carries mortality rates of 40 to 70 percent in its most aggressive presentations and accounts for a significant fraction of transplant-related deaths.

The Fred Hutch antibody, designated FH-EBV-1, targets the gp350 surface glycoprotein on the EBV viral envelope, the protein the virus uses to bind to the CD21 receptor on B cells and initiate entry. The antibody was developed using a structure-guided approach that identified the binding epitope most critical for viral entry and then optimized an antibody to block that site with high affinity. In animal models, a single dose conferred protection for several months, and the clinical trial used a dosing regimen of two infusions given one week apart at the time of transplantation, timed to establish protective antibody levels before patients entered the period of deepest immunosuppression.

The trial enrolled patients receiving allogeneic stem cell transplants for leukemia, lymphoma, and inherited blood disorders, as well as patients receiving solid organ transplants including kidney and liver. In both populations, the antibody significantly reduced the rate of EBV viremia — detectable virus in the blood — and the rate of progression to lymphoproliferative disease compared to patients who received a placebo infusion. No serious adverse events attributable to the antibody were observed, and the safety profile was considered favorable by the trial's independent safety monitoring board.

Fred Hutch has licensed the antibody to a biopharmaceutical partner for phase 3 development, with an expanded trial expected to begin enrollment by the end of 2026. If phase 3 results confirm phase 2 efficacy, researchers estimated the antibody could be in clinical use for transplant patients by 2029, offering the first preventive option for EBV-related complications beyond antiviral drugs like ganciclovir, which prevent cytomegalovirus but are not active against EBV.