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Herpes simplex virus type 2 glycoprotein D (gD-2) is a critical structural component of the HSV-2 viral envelope. It serves as the primary ligand for host cell receptors, including Nectin-1 and Herpesvirus entry mediator (HVEM), facilitating the initial attachment and subsequent fusion of the viral envelope with the host cell membrane (UniProt P06476). Because gD-2 is essential for viral infectivity and is a major target for neutralizing antibodies, it has been the focus of numerous vaccine and monoclonal antibody development efforts (PubMed 22216470). Therapeutic strategies targeting gD-2 aim to block viral entry into host cells, thereby preventing primary infection or reducing the frequency and severity of viral reactivation in chronic cases (PubMed 33106334). Despite its promise, clinical trials for gD-2-based vaccines have faced challenges, including varying efficacy across different patient populations and the need for robust T-cell responses alongside antibody production (PubMed 31619554). Current research continues to explore gD-2 as a target for passive immunization using monoclonal antibodies like UB-621 and HDIT101 (PubMed 33106334).
Neutralization of viral entry and cell-to-cell spread by blocking the interaction between gD-2 and host receptors such as Nectin-1 and HVEM, which prevents the conformational change required to activate the viral fusion machinery (gB and gH/gL).
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