What does this research mean for the field?

gB-specific antibodies protect neonatal mice from HSV mortality primarily through Fc effector functions, rather than solely through viral neutralization. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

March 12, 2026Open Access

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

Key Result

gB-specific antibodies protected neonatal mice from HSV mortality primarily through Fc effector functions, rather than solely viral neutralization.

Key Points

To investigate how glycoprotein B-specific monoclonal antibodies protect against herpes simplex virus in neonatal mice.
Used a mouse model of neonatal HSV infection
Administered various doses of gB-specific monoclonal antibodies
Evaluated the role of viral neutralization and Fc effector functions in protection
Assessed transgenerational protection via adeno-associated virus-mediated expression of mAbs
Fc effector functions are critical for monoclonal antibody-mediated protection against nHSV mortality
Viral neutralization contributed depending on antibody dose
Adeno-associated virus delivery of gB-specific antibodies provided long-lasting protection against HSV-1 and HSV-2

Structured PICO

Do gB-specific monoclonal antibodies protect against neonatal HSV mortality in mice?

Population

Mouse model of neonatal HSV (nHSV) infection

Intervention

Panel of gB-specific monoclonal antibodies (mAbs) and adeno-associated virus-mediated in vivo expression of a gB-specific mAb

Outcome

Protection against nHSV mortality (HSV-1 and HSV-2)hard clinical

Antibodies targeting HSV glycoprotein B require Fc domain-dependent effector functions to provide optimal protection against neonatal HSV mortality in mice.

Main Result

Absolute Event Rate: 0% vs 0%

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 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 (mAbs) in a mouse model of neonatal HSV (nHSV) infection. Depending on dose, viral neutralization contributed, but Fc effector functions were critical for mAb-mediated protection against nHSV mortality. Moreover, adeno-associated virus-mediated in vivo expression of a gB-specific mAb in mice provided transgenerational protection against HSV-1 and HSV-2 mortality. 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.IMPORTANCEAntibodies represent promising drugs for the prevention and treatment of viral infections, especially when efficacious vaccines are unavailable. Determining the dominant mechanisms of Ab-mediated protection is a critical step in the design and optimization of potential antibody therapies. In this study of antibody-mediated protection of neonatal mice from herpes simplex virus, efficacy and mechanism of action of antibodies that recognize viral glycoprotein B (gB) were dependent on dose, effector functions, and viral neutralization capacity. Overall, while viral neutralization likely contributes to monoclonal antibody-mediated protection, the ability for gB-specific antibodies to mediate Fc domain-dependent effector functions was unexpectedly crucial.