New Antibody Shows Promise in Blocking Epstein-Barr Virus

A new approach using genetically human monoclonal antibodies is offering hope for controlling Epstein-Barr virus (EBV), a widespread pathogen linked to various cancers, neurodegenerative diseases, and other chronic health conditions. Researchers at Fred Hutch Cancer Center have achieved a significant milestone in developing antibodies that can block EBV infection.

Understanding Epstein-Barr Virus

EBV is remarkably common, infecting an estimated 95% of the global population . While many individuals remain asymptomatic, EBV can cause infectious mononucleosis and is associated with an increased risk of several serious illnesses, including certain lymphomas and potentially multiple sclerosis .

The Challenge of Blocking EBV

Developing effective antibodies against EBV has proven tricky because the virus can bind to nearly all B cells, a type of immune cell . This widespread binding makes it challenging to create antibodies that can effectively neutralize the virus without triggering unwanted immune responses.

A Novel Antibody Approach

Researchers utilized a unique approach, employing mice with human antibody genes to generate genetically human monoclonal antibodies. These antibodies are designed to prevent EBV from attaching to and entering human immune cells by targeting two key viral surface proteins: gp350 and gp42 . The study, published in Cell Reports Medicine, identified one antibody that successfully blocked infection in mice with human immune systems when challenged with EBV .

Targeting Viral Proteins

The research focused on two specific viral proteins crucial for EBV infection:

• gp350: Facilitates the initial binding of EBV to receptors on human cells.
• gp42: Enables the virus to fuse with and enter human cells .

The team generated two monoclonal antibodies against gp350 and eight against gp42 using the specialized mouse model .

Hope for Transplant Patients

This breakthrough holds particular promise for transplant recipients, who are at high risk of EBV-related complications. These patients require immunosuppressant drugs to prevent organ rejection, which weakens their immune defenses and makes them vulnerable to EBV infection and post-transplant lymphoproliferative disease (PTLD), a potentially life-threatening lymphoma . Currently, there are no targeted treatments to reliably prevent EBV infection or reactivation in these patients .

Future Directions

Researchers are now working towards developing a therapy involving the infusion of these monoclonal antibodies into high-risk patients. The goal is to prevent EBV infection or reactivation and reduce the incidence of PTLD . Fred Hutch has filed for intellectual property protection for the identified antibodies and is collaborating with industry partners to advance the potential therapy through safety testing and clinical trials .

“There’s momentum to advance our discovery to a therapy that would make a huge difference for patients undergoing transplant,” said Andrew McGuire, PhD .