Scientists at the National Institutes of Health have identified structural weak points on the Epstein-Barr virus that allowed them to develop a monoclonal antibody capable of blocking infection in animal models. The lead antibody, called A10, targets a viral protein known as gp42 and delivered near-complete protection against both viremia and EBV-linked lymphomas in mice engineered with human immune systems. Because EBV infects the vast majority of adults worldwide and has been linked to cancers and autoimmune conditions like multiple sclerosis, the findings open a new front in the decades long effort to prevent the virus from gaining a foothold in the body.
Why gp42 Changes the Target Calculus
For years, vaccine and antibody research against EBV focused heavily on a surface protein called gp350, which the virus uses to latch onto a receptor known as CR2 on B cells. Structural studies at the National Institute of Allergy and Infectious Diseases mapped how neutralizing antibodies bind to gp350 and block that initial attachment. Yet gp350-only strategies proved incomplete. The virus still managed to fuse with and enter B cells through a separate mechanism, leaving a gap that single-target approaches could not close.
The new work shifts attention to gp42, a glycoprotein that mediates the fusion step, the moment EBV actually merges with a B cell’s membrane. Researchers isolated monoclonal antibodies, including A10 and a second candidate called 4C12, that bind to distinct vulnerability sites on gp42. Structural biology techniques revealed that these sites govern both receptor binding and the conformational changes required for fusion. Blocking them effectively jams the lock the virus needs to open, rather than simply preventing it from reaching the door.
Near-Complete Protection in Humanized Mice
The strongest evidence for the gp42 approach comes from passive-transfer experiments in humanized mice, animals whose immune systems have been reconstituted with human cells so they can support EBV infection. When researchers administered the A10 antibody before exposing the mice to the virus, the results were striking: NIH scientists reported near-complete protection from EBV infection and from the lymphoproliferative disease and lymphoma that EBV can trigger in immunocompromised hosts. Separate work published in a peer-reviewed journal confirmed that gp42 CTLD-targeting neutralizing antibodies protected humanized mice from lethal EBV challenge and EBV-induced lymphoma, while also mapping the specific neutralizing epitopes involved.
These animal results carry weight because humanized-mouse models are among the closest available surrogates for human EBV infection. Still, mouse data does not automatically translate to clinical success. No human trial results exist yet, and the jump from rodent protection to a viable therapy or prophylactic involves pharmacokinetic, dosing, and safety questions that remain unanswered. The protection signal is real, but it is preclinical. That distinction matters for anyone tracking this research toward a product.
Dual-Target Strategy and the Case for Combination
One of the more consequential implications of the gp42 findings is what they mean alongside existing gp350 data. A study published in Cell Reports Medicine generated and characterized genetically human monoclonal antibodies against both EBV gp350 and gp42, demonstrating that the antibodies neutralize the virus and block entry factors in vitro while also providing in vivo protection in humanized-mouse challenge models. The logic is straightforward: gp350 antibodies interrupt the virus’s initial attachment to B cells, while gp42 antibodies shut down the fusion machinery. Pairing them could cover two independent steps in the infection process, reducing the odds that the virus slips through.
Additional vaccine research supports this dual-target thinking. A study in npj Vaccines showed that immune responses targeting EBV entry machinery, including the gH/gL complex, protected humanized mice from EBV-driven tumor formation and death after high-dose challenge when vaccine-elicited IgG was transferred. That work also found that constructs incorporating gH/gL/gp42 and gp350 generated neutralizing titers. Taken together, the evidence points toward a multi-antigen strategy as the most promising path, though no single trial has yet tested a combined gp350-plus-gp42 antibody cocktail in humans.
From Lab Bench to Licensing
The NIH has already moved to position these antibodies for commercial development. The agency’s technology transfer office lists the gp42-specific antibodies as an invention available for licensing, describing their functional properties: neutralizing EBV infection and inhibiting fusion with B cells. The listing also flags proposed prophylactic and therapeutic applications in immunocompromised patients, a population that includes organ transplant recipients and people living with HIV, who face elevated risks of EBV-associated cancers.
According to a EurekAlert announcement, the antibody was described as a first-of-its-kind development, though the precise timeline for clinical testing has not been publicly detailed. A separate report from Reuters indicated that an antibody against gp42 prevented infection in mice with human immune systems exposed to EBV, but that account placed the announcement date at February 25, 2026, while the EurekAlert notice referenced an earlier briefing. The discrepancy underscores how fast-moving preclinical findings can be communicated in overlapping ways, even as the underlying science (structural targeting of gp42 to block fusion) remains consistent across outlets.
What This Means for Patients and Public Health
For patients and clinicians, the promise of gp42-targeted antibodies lies in the possibility of finally having a tool to prevent primary EBV infection or reactivation in high-risk groups. EBV is so widespread that most people acquire it in childhood or adolescence, often with mild or no symptoms, but it can cause infectious mononucleosis and contribute to certain lymphomas, nasopharyngeal carcinoma, and post-transplant lymphoproliferative disease. Resources such as MedlinePlus already emphasize how few specific treatments exist for EBV beyond supportive care, highlighting the gap that a prophylactic antibody or vaccine could fill. If gp42-based products reach the clinic, they may initially be deployed in narrow settings (such as before organ transplantation or in people with profound immune suppression) before broader preventive uses are considered.
At the same time, the broader public health impact of EBV research extends beyond any single antibody. Educational platforms like NIH Science Education and the consumer-friendly stories in NIH News in Health help translate complex virology and immunology into language that patients, families, and students can understand. As gp42-focused strategies advance, clear communication about what has been shown in mice, what remains untested in humans, and how these approaches fit alongside vaccine candidates will shape expectations. For now, the A10 antibody and related gp42-directed molecules represent a compelling proof of concept: by mapping and exploiting structural weak points on EBV’s fusion machinery, researchers have opened a realistic path toward interventions that do more than blunt symptoms—they aim to stop the virus before it ever takes hold.
More from Morning Overview
*This article was researched with the help of AI, with human editors creating the final content.
