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Backes, Iara M; Byrd, Brook K; Slein, Matthew D; Patel, Chaya D; Taylor, Sean A; Garland, Callaghan R; MacDonald, Scott W; Balazs, Alejandro B; Davis, Scott C; Ackerman, Margaret E; Leib, David A
The Journal of experimental medicine, 12/2022, Volume: 219, Issue: 12Journal Article
Neonatal herpes simplex virus (nHSV) infections often result in significant mortality and neurological morbidity despite antiviral drug therapy. Maternally transferred herpes simplex virus (HSV)-specific antibodies reduce the risk of clinically overt nHSV, but this observation has not been translationally applied. Using a neonatal mouse model, we tested the hypothesis that passive transfer of HSV-specific human mAbs can prevent mortality and morbidity associated with nHSV. The mAbs were expressed in vivo via vectored immunoprophylaxis or recombinantly. Through these maternally derived routes or through direct administration to pups, diverse mAbs to HSV glycoprotein D protected against neonatal HSV-1 and HSV-2 infection. Using in vivo bioluminescent imaging, both pre- and post-exposure mAb treatment significantly reduced viral load in mouse pups. Together these studies support the notion that HSV-specific mAb-based therapies could prevent or improve HSV infection outcomes in neonates.
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