Herpes simplex virus type 2 glycoprotein D (gD2) (HSV-2 gD)

Herpes simplex virus type 2 glycoprotein D (gD2) is an essential envelope protein required for viral attachment and entry into host cells by binding to cellular receptors such as nectin-1 and herpesvirus entry mediator (HVEM) (Belshe et al., 2012, N Engl J Med). In the context of the Simplirix vaccine candidate, a truncated version of this protein (gD2t) is combined with the AS04 adjuvant system, which consists of 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and aluminum hydroxide (Didierlaurent et al., 2009, Expert Rev Vaccines). This formulation is designed to stimulate the immune system to produce high-titer neutralizing antibodies and a Th1-biased cellular response to prevent infection or reduce the severity of genital herpes. The AS04 adjuvant specifically enhances the immune response by activating Toll-like receptor 4 (TLR4), leading to increased antigen-presenting cell activity and cytokine production (Garçon et al., 2007, Expert Rev Vaccines). While the gD2-AS04 candidate demonstrated efficacy in preventing HSV-1 infection and disease in women who were seronegative for both HSV-1 and HSV-2, it failed to provide significant protection against HSV-2 in large-scale Phase III clinical trials (Belshe et al., 2012). Despite these challenges, gD2 remains a primary focus for subunit vaccine development due to its critical role in viral membrane fusion and cell-to-cell spread.

Other names

gD2Glycoprotein D-2HSV-2 gD antigenSimplirix antigengD2tHerpes simplex virus type 2 glycoprotein D

Induction of neutralizing antibodies and Th1-biased cellular immune responses to block viral entry and fusion.