Effector functions are required for broad and potent protection of neonatal mice with antibodies targeting HSV glycoprotein D.
Cell Rep Med
; 5(2): 101417, 2024 Feb 20.
Article
en En
| MEDLINE
| ID: mdl-38350452
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Vacunas Virales
/
Herpes Simple
Límite:
Animals
/
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article