Antibodies targeting HSV glycoprotein B require effector functions to protect neonatal mice

Slein, M. D.; Jimenez, L. M.; Backes, I. M.; Turnbaugh, E. M.; Garland, C. R.; MacDonald, S. W.; Balazs, A. B.; Leib, D. A.; Ackerman, M. E.

doi:10.1101/2025.07.25.666806

bioRxiv · 10.1101/2025.07.25.666806

Antibodies targeting HSV glycoprotein B require effector functions to protect neonatal mice

Slein, M. D.·Jimenez, L. M.·Backes, I. M.·Turnbaugh, E. M.·Garland, C. R.·MacDonald, S. W.·Balazs, A. B.·Leib, D. A.·Ackerman, M. E.

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Abstract

Glycoprotein B (gB) serves as the viral fusion protein for herpes simplex virus (HSV), mediating fusion between viral and host membranes resulting in infection. As such, gB represents a potentially critical target for the host immune system with high potential relevance for vaccine design. Here we investigated the mechanisms of protection for a panel of gB-specific monoclonal antibodies (mAb) in a mouse model of neonatal HSV (nHSV) infection. Viral neutralization contributed, but Fc effector functions were critical for mAb-mediated protection against nHSV mortality, depending on dose. Moreover, AAV-mediated in vivo expression of a gB-specific mAb in mice provided transgenerational protection against HSV-1 and HSV-2 mortality in their offspring. These findings demonstrate that antibodies targeting gB can serve as potent therapeutics and that they require diverse functional profiles to afford optimal protection, informing vaccine design.

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Slein, M. D., Jimenez, L. M., Backes, I. M., Turnbaugh, E. M., Garland, C. R., MacDonald, S. W., Balazs, A. B., Leib, D. A., Ackerman, M. E.. 2025-07-30. Antibodies targeting HSV glycoprotein B require effector functions to protect neonatal mice. https://doi.org/10.1101/2025.07.25.666806

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