New Antibody Candidates Offer Hope Against Epstein-Barr Virus

Researchers at the Fred Hutchinson Cancer Center and the University of Washington have engineered antibodies that bind the Epstein-Barr virus surface proteins gp350 and gp42. In humanized mice, one antibody prevented infection, marking the first preclinical demonstration of protective immunity against EBV.

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The Epstein-Barr virus infects roughly 95 % of adults worldwide, often without symptoms. After initial exposure, the virus establishes lifelong latency and has been linked to several cancers, multiple sclerosis, post-transplant lymphoproliferative disorder, and other severe health complications.

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The study was led by biochemist Andrew McGuire and pathobiologist Crystal Chhan, with infectious disease physician Rachel Bender Ignacio contributing clinical insight. It was conducted jointly by the Fred Hutchinson Cancer Center and the University of Washington in Seattle.

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The team isolated ten human-compatible antibodies—two against gp350 and eight against gp42—using mice engineered to produce fully human antibodies. In humanized mice, one antibody blocked EBV entry and replication, showing in-vivo protection.

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The antibodies could be given to organ and bone-marrow transplant patients, who are immunosuppressed and at risk for EBV-driven PTLD. Blocking infection may lower PTLD rates and reduce the need to taper immunosuppression, particularly in children.

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McGuire emphasized the challenge of finding EBV-blocking antibodies because the virus binds nearly every B cell, calling it a stride. Chhan called the work a validation of a platform for discovering protective antibodies against other pathogens. Ignacio noted the potential to reduce PTLD and immunosuppression in transplant patients.

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The protective effect has been demonstrated only in humanized mouse models; no human safety or efficacy data are available. Dosage, pharmacokinetics, and long-term outcomes remain uncharacterized, and the translation of murine results to clinical practice is uncertain pending trial results.

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• "Finding human antibodies that block Epstein-Barr virus from infecting our immune cells has been particularly challenging because, unlike other viruses, EBV finds a way to bind to nearly every one of our B cells," — Andrew McGuire, biochemist

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• "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," — Crystal Chhan, pathobiologist

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• "Preventing EBV viremia has strong potential to reduce the incidence of PTLD and limit the need to reduce immunosuppression," — Rachel Bender Ignacio, infectious disease physician

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• "After many years of searching for a viable way to protect against Epstein-Barr virus, this is a significant stride for the scientific community and the people at the highest risk of complications from this virus," — Andrew McGuire, biochemist

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The investigators plan to advance the lead antibody into human safety assessments, followed by Phase I clinical trials. Further optimization of dosing and delivery will be pursued, and the antibody discovery platform may be applied to additional viral targets. The study appears in *Cell Reports Medicine*.

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