Design, Structure, and Immunogenicity of a Soluble Prefusion-stabilized EBV gB Antigen.

ABSTRACT: Epstein-Barr virus (EBV), the causative agent of mononucleosis, is linked to over 140,000 annual cancer-related deaths globally and increases the risk of multiple sclerosis by up to 32-fold. As a herpesvirus, EBV establishes lifelong infection, and over 90% of U.S. adults are EBV-seropositive. Despite its significant disease burden, no approved EBV vaccines or therapeutics exist. Among EBV envelope glycoproteins, the fusion protein (gB) is strictly required for epithelial and B cell infection. Using a combination of AlphaFold-guided modeling, rational design, and ThermoMPNN-informed optimization, we engineered a stabilized prefusion gB variant, D2C3. This construct incorporates two inter-protomeric disulfide bonds and three cavity-filling substitutions, resulting in a melting temperature o

SUBMITTER: McCool RS 

PROVIDER: S-EPMC12258704 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature