Glycoprotein D-specific monoclonal antibodies required effector functions for protection against neonatal HSV-1 and HSV-2 in a mouse model.
Do gD-specific monoclonal antibodies protect against neonatal HSV infection via Fc-domain-dependent effector functions?
Fc-domain-dependent effector functions of gD-specific monoclonal antibodies are crucial for protecting neonatal mice against HSV infections, informing future vaccine and therapeutic designs.
Multiple failed herpes simplex virus (HSV) vaccine candidates induce robust neutralizing antibody (Ab) responses in clinical trials, raising the hypothesis that Fc-domain-dependent effector functions may be critical for protection. While neonatal HSV (nHSV) infection results in mortality and lifelong neurological morbidity in humans, it is uncommon among neonates with a seropositive birthing parent, supporting the hypothesis that Ab-based therapeutics could protect neonates from HSV. We therefore investigated the mechanisms of monoclonal Ab (mAb)-mediated protection in a mouse model of nHSV infection. For a panel of glycoprotein D (gD)-specific mAbs, neutralization and effector functions contributed to nHSV-1 protection. In contrast, effector functions alone were sufficient to protect against nHSV-2, exposing a functional dichotomy between virus types consistent with vaccine trial results. Effector functions are therefore crucial for protection by these gD-specific mAbs, informing effective Ab and vaccine design and demonstrating the potential of polyfunctional Abs as therapeutics for nHSV infections.
Slein et al. (Thu,) conducted a other in neonatal HSV (nHSV) infection. glycoprotein D (gD)-specific monoclonal antibodies was evaluated on protection against nHSV-1 and nHSV-2. Glycoprotein D-specific monoclonal antibodies required effector functions for protection against neonatal HSV-1 and HSV-2 in a mouse model.
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