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Prefusion-specific glycoprotein B human antibodies protect against neonatal HSV-2 infection

2026/02/24 by Parastoo Amlashi, JeongRyeol Kim, Nisali N. Mendis +11 · 1 voice · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · #Herpesvirus Infections and Treatments #Cytomegalovirus and herpesvirus research #Virus-based gene therapy research

paper · doi:10.64898/2026.02.23.707514

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.

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