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

Amlashi, P.; Kim, J.; Mendis, N. N.; Wasdin, P. T.; Bass, L. E.; Jordaan, G.; Abu-Shmais, A. A.; Slein, M. D.; Johnson, N. V.; Bonami, R. H.; Leib, D. A.; Ackerman, M. E.; McLellan, J. S.; Georgiev, I.

doi:10.64898/2026.02.23.707514

bioRxiv · 10.64898/2026.02.23.707514

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

Amlashi, P.·Kim, J.·Mendis, N. N.·Wasdin, P. T.·Bass, L. E.·Jordaan, G.·Abu-Shmais, A. A.·Slein, M. D.·Johnson, N. V.·Bonami, R. H.·Leib, D. A.·Ackerman, M. E.·McLellan, J. S.·Georgiev, I.

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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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Amlashi, P., Kim, J., Mendis, N. N., Wasdin, P. T., Bass, L. E., Jordaan, G., Abu-Shmais, A. A., Slein, M. D., Johnson, N. V., Bonami, R. H., Leib, D. A., Ackerman, M. E., McLellan, J. S., Georgiev, I.. 2026-02-24. Prefusion-specific glycoprotein B human antibodies protect against neonatal HSV-2 infection. https://doi.org/10.64898/2026.02.23.707514

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