bioRxivImmunologyPreprint
Prefusion-specific glycoprotein B human antibodies protect against neonatal HSV-2 infection
Parastoo AmlashiiD, 김정렬, Nisali N. Mendis, Perry T. WasdiniD, Lindsay E BassiD, Gwen Jordaan, Alexandra A. Abu-ShmaisiD, Matthew D. SleiniD, Nicole V. JohnsoniD, Rachel H. BonamiiD, David A. LeibiD, Margaret E. AckermaniD, Jason S. McLellaniD, Ivelin S. GeorgieviD
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.
- organism: human
- assay: proteomics
- research focus: host-pathogen & immune response
- approach: experimental assay
- approach: deep learning
- Citations
- 1
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