Researchers have developed an effective way to block the Epstein-Barr virus, a widespread infection that affects about 95% of the world's population and is linked to several types of cancer, neurodegenerative diseases, and other chronic illnesses.
The team used genetically modified mice to produce human antibodies, and were able to create monoclonal antibodies that prevent the virus from attaching to and entering human immune cells.
The results, published in the journal Cell Reports Medicine, showed that one of these antibodies was able to completely prevent infection in mice with human-like immune systems.
Dr. Andrew McGuire, a biochemist and cell biologist in the Vaccine and Infectious Disease Branch at the Fred Hatch Center, said: "Finding human antibodies that block the virus was particularly difficult because, unlike other viruses, the Epstein-Barr virus finds a way to bind to almost all immune B cells. But we used new techniques and were able to bridge this knowledge gap, achieving a crucial step towards blocking one of the most common viruses in the world."
The researchers faced a major obstacle: finding antibodies that would neutralize the virus without triggering an immune response against the treatment itself, a common occurrence when antibodies come from non-human sources. To overcome this, the team focused on two viral proteins: gp350, which helps the virus attach to human cells, and gp42, which allows the virus to fuse with and enter cells.
Using a modified mouse model, scientists were able to identify one antibody targeting the gp350 protein, and eight antibodies targeting the gp42 protein.
“We not only discovered important antibodies against the virus, but we also demonstrated the effectiveness of a novel and innovative approach that can be used to discover protective antibodies against other pathogens,” said Crystal Chan, a PhD student in McGuire’s lab.
Further analysis also revealed specific weaknesses on the virus's surface, which could aid in the design of future vaccines. In final tests, an antibody targeting the gp42 protein completely blocked infection, while an antibody targeting gp350 provided only partial protection.
Each year, a large number of people worldwide receive solid organ or bone marrow transplants. These patients often require immunosuppressant drugs, which can allow the virus to reactivate or spread unchecked, and there are currently no targeted treatments to prevent this.
Post-transplant lymphoproliferative disorders are a serious form of lymphoma that can develop after transplantation, and are often caused by uncontrolled Epstein-Barr virus infection.
present in the bloodstream could significantly reduce the occurrence of these disorders and limit the need for immunosuppression, thus helping to preserve transplanted organ function and improve patient outcomes. She emphasized that preventing the virus remains an unmet need in transplant medicine.
Patients may be exposed to the virus through donor organs that carry a latent form of it, or immunosuppression may reactivate the virus in those who have previously been infected. Children undergoing transplants are particularly vulnerable, as many have never been exposed to the virus before.
The research team envisions administering these antibodies intravenously to prevent infection or reactivation, particularly in high-risk groups. By blocking the virus early, this treatment could help prevent serious complications.
The center has filed intellectual property protection applications for these antibodies. Researchers are now working with industry partners to bring this discovery closer to clinical use. The next steps include safety testing in healthy adults, followed by clinical trials in high-risk patients.
Dr. McGuire concluded, "There is great momentum to turn our discovery into a treatment that makes a big difference to transplant patients. After many years of searching for a way to protect against this virus, we have achieved an important step for the scientific community and for those most vulnerable to its complications."
