Envelope glycoprotein D (Herpes simplex virus 2) (gD2)

Envelope glycoprotein D (gD2) is a critical surface protein of the Herpes simplex virus type 2 (HSV-2) that is essential for viral entry into host cells and subsequent cell-to-cell spread. It functions by binding to specific host cell receptors, including Nectin-1, Nectin-2, and the Herpesvirus Entry Mediator (HVEM), which triggers the fusion of the viral envelope with the host cell membrane. As a primary immunodominant antigen, gD2 has been the central focus of numerous prophylactic and therapeutic vaccine candidates, such as the GSK gD2 subunit vaccine (Simplirix) and Genocea's GEN-003. Despite its ability to induce high titers of neutralizing antibodies, many gD2-based subunit vaccines have shown limited clinical efficacy in preventing HSV-2 infection, leading to ongoing research into multi-antigen vaccines and monoclonal antibodies. Beyond its role in entry, gD2 is involved in immune evasion by modulating T-cell and NK-cell responses, making it a complex but vital target for controlling genital herpes and reducing the risk of neonatal transmission and HIV acquisition.

Other names

gD-2US6HSV-2 glycoprotein DEnvelope glycoprotein D2Glycoprotein D (HSV-2)

Neutralization of viral entry by blocking receptor binding and induction of antibody-dependent cellular cytotoxicity (ADCC) and T-cell mediated immunity.