Chhan et al. (2026)
- Authors: Chhan CB, Lang K, Davis AR, Wan YH, Aldridge NT, Kher G, Scharffenberger SC, Hardy SR, Iureniev R, Giltiay NV, Edwards KR, Radtke S, Kiem HP, Pancera M, McGuire AT
- Institutes: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, Department of Global Health, University of Washington, Seattle, WA, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, Stem Cell and Gene Therapy Program, Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA
- Publisher: Cell Reports Medicine
- Link: DOI
Summary
This research provides a potential breakthrough for individuals at risk of EBV-related complications, including those with ME/CFS and Multiple Sclerosis where EBV is often implicated as a driver of disease. By creating the first human-type antibodies that can effectively block viral entry, the study moves closer to a long-awaited treatment for one of the world’s most common viruses. The identification of specific binding sites also accelerates the progress toward a preventative EBV vaccine.
What was researched?
This study explored the development and effectiveness of human monoclonal antibodies derived from transgenic mice that target the Epstein-Barr virus (EBV) glycoproteins gp350 and gp42.
Why was it researched?
EBV is a widespread virus linked to infectious mononucleosis, various cancers, and autoimmune conditions like Multiple Sclerosis, yet there are currently no approved vaccines or targeted treatments.
How was it researched?
Researchers used a specialized transgenic mouse model to generate ten genetically human neutralizing antibodies. These antibodies were then tested in ‘humanized’ mice with human immune systems to evaluate their ability to prevent EBV infection and structural analyses were conducted to map their binding sites.
What has been found?
The study identified a gp42 mAb 💊 that provided significant protection against EBV infection in mice, while a gp350 mAb 💊 offered partial protection. These antibodies successfully blocked the virus from attaching to receptors on B cells, which is the primary route the virus uses to infect the human immune system.
Discussion
The use of transgenic mice allowed for the creation of fully human antibodies, which are less likely to be rejected by the human immune system than previous non-human versions. Structural mapping of these antibodies revealed new ‘sites of vulnerability’ on the virus that could be critical for future vaccine design.
Conclusion & Future Work
The researchers concluded that these human monoclonal antibodies are promising candidates for preventing EBV-related diseases in high-risk patients, such as organ transplant recipients. This work provides a foundation for the clinical development of both therapeutic antibodies and preventive vaccines.