Prefusion-specific glycoprotein B human antibodies protect against neonatal HSV-2 infection
Year: 2026
Type: preprint
Abstract: Herpes simplex virus (HSV) causes severe neonatal infections and long-term neurological issues, with antivirals offering limited efficacy and no approved vaccines. Viral entry requires glycoprotein B (gB) for membrane fusion, yet no human antibodies to the prefusion form of gB have been identified, and antibodies targeting vulnerable epitopes are limited. We used prefusion-stabilized HSV-2 gB and LIBRA-seq technology to analyze B cells from seropositive and healthy donors, discovering four prefusion-specific human antibodies binding unique gB epitopes as determined by cryo-EM. Antibodies 5-18 and 3-6 showed strong cross-neutralization against HSV-1 and HSV-2, offering protection in a neonatal mouse model. These findings highlight the molecular and structural determinants of HSV-2 prefusion gB recognition by human antibodies and demonstrate the translational potential of prefusion-specific gB antibodies.
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G5536297675, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, VANTAGE:Consolidation to create the Vanderbilt Technologies for Advanced Genomics, The Origins of Human Anti-Insulin B Lymphocytes in Type 1 Diabetes, Molecular and Cellular Basis for Digestive Diseases, Evolution of B Lymphocyte Insulin Autoantigen Recognition in Type 1 Diabetes, Cancer Center Support Grant, Understanding and optimizing antibody-based interventions against neonatal HSV infection, Technologies for High-Throughput Mapping of Antigen Specificity to B-Cell-Receptor Sequence, Core Grant in Vision Research
OpenAlex ID: W7131360674