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TitleTransgenic mouse-derived human monoclonal antibodies targeting EBV gp350 and gp42 provide basis for therapeutic development.
Journal, issue, pagesCell Rep Med, Vol. 7, Issue 2, Page 102618, Year 2026
Publish dateFeb 17, 2026
AuthorsCrystal B Chhan / Kevin Lang / Amelia R Davis / Yu-Hsin Wan / Nicholas T Aldridge / Gargi Kher / Samuel C Scharffenberger / Samantha R Hardy / Roman Iureniev / Natalia V Giltiay / Kristina R Edwards / Stefan Radtke / Hans-Peter Kiem / Marie Pancera / Andrew T McGuire /
PubMed AbstractEpstein-Barr virus (EBV) causes infectious mononucleosis and contributes to neurodegenerative disorders and malignancies, particularly in immune-compromised hosts. Transplant patients face high risk ...Epstein-Barr virus (EBV) causes infectious mononucleosis and contributes to neurodegenerative disorders and malignancies, particularly in immune-compromised hosts. Transplant patients face high risk of post-transplant lymphoproliferative disease, a life-threatening EBV-driven lymphoma. There are no EBV-specific vaccines or treatments; however, neutralizing antibodies against EBV glycoproteins may offer utility as therapeutic agents. EBV entry into B cells involves gp350, which binds complement receptors, and gp42, which engages HLA class II to trigger fusion. Most existing monoclonal antibodies (mAbs) against these antigens are non-human, limiting clinical use. Using a transgenic mouse model, we generate two gp350 and eight gp42 genetically human neutralizing mAbs that block receptor binding. Structural analyses reveal extended sites of vulnerability relevant to vaccine development. Delivery of a gp42 mAb protects humanized mice from EBV challenge, while a gp350 mAb provides partial protection. These mAbs highlight the utility of transgenic mice to produce therapeutic mAbs for preventing EBV-driven disease.
External linksCell Rep Med / PubMed:41707657 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.93 - 9.86 Å
Structure data

EMDB-71585: Negative stain EM map of EBV glycoprotein gH/gL in complex with glycoprotein gp42 and FAB ATX-42-1.1 open conformation
Method: EM (single particle) / Resolution: 9.86 Å

EMDB-71586: Negative stain EM map of EBV glycoprotein gH/gL in complex with glycoprotein gp42 and FAB ATX-42-2 Open conformation
Method: EM (single particle) / Resolution: 8.45 Å

PDB-9pf9:
X-ray crystal structure of ATX-350-2 Fab bound to Epstein-Barr virus glycoprotein 350
Method: X-RAY DIFFRACTION / Resolution: 3.93 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-HOH:
WATER

Source
  • human gammaherpesvirus 4 (Epstein-Barr virus)
  • mus musculus (house mouse)
KeywordsIMMUNE SYSTEM / Viral protein / Complex / Antibody / EBV

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