Researchers at Fred Hutch Cancer Center have created human-like monoclonal antibodies that prevent Epstein-Barr virus (EBV) from infecting immune cells. Using mice engineered with human antibody genes, the team identified antibodies targeting viral proteins gp350 and gp42, with one fully blocking infection in lab models. The findings, published in Cell Reports Medicine, could lead to therapies for transplant patients at risk of EBV-related complications.
Fred Hutch Cancer Center scientists advanced efforts against Epstein-Barr virus, which infects about 95% of people worldwide and links to cancers and chronic diseases. The team used specialized mice to produce human antibodies that target EBV's entry into B cells, a challenge due to the virus's broad binding ability. They identified two antibodies against gp350, which aids attachment, and eight against gp42, which enables cell fusion. Analysis pinpointed viral weak spots for future vaccines, supported by Fred Hutch's Antibody Tech Core. One gp42-targeting antibody completely prevented infection in mice with human-like immune systems, while a gp350 antibody provided partial protection. Andrew McGuire, PhD, a biochemist in the Vaccine and Infectious Disease Division at Fred Hutch, said, 'Finding human antibodies that block Epstein Barr virus from infecting our immune cells has been particularly challenging... We ended up taking a critical step toward blocking one of the world's most common viruses.' Crystal Chhan, a pathobiology PhD student in the McGuire Lab, noted, 'Not only did we identify important antibodies against Epstein Barr virus, but we also validated an innovative new approach for discovering protective antibodies against other pathogens.' The breakthrough holds promise for transplant patients, where over 128,000 Americans receive organs or bone marrow yearly. Immunosuppressive drugs can reactivate latent EBV, leading to post-transplant lymphoproliferative disorders (PTLD), often EBV-driven lymphomas. Rachel Bender Ignacio, MD, MPH, an infectious disease physician at Fred Hutch and University of Washington School of Medicine, stated, 'Preventing EBV viremia has strong potential to reduce the incidence of PTLD and limit the need to reduce immunosuppression.' Fred Hutch has filed intellectual property claims on the antibodies, with McGuire and Chhan collaborating toward clinical trials.
