Herpes simplex virus type 2 ICP4 and glycoprotein D2 antigens (HSV-2 ICP4/gD2)

Herpes simplex virus type 2 (HSV-2) antigens ICP4 and glycoprotein D (gD2) are the primary components of the therapeutic vaccine candidate GEN-003, designed to treat genital herpes (Wald et al., 2016, JCI Insight). ICP4 (Infected Cell Protein 4) is a large, essential immediate-early protein that functions as a transcriptional activator for early and late viral genes, making it a critical target for T-cell mediated immunity (Skoberne et al., 2013, Vaccine). Glycoprotein D (gD2) is an envelope protein essential for viral entry into host cells via interaction with receptors like HVEM and nectin-1, and it is the primary target for neutralizing antibodies (Bernstein et al., 2014, Vaccine). The specific constructs used in immunotherapy include ICP4.2, a recombinant fragment of the ICP4 protein, and gD2ΔTMR, a truncated version of glycoprotein D lacking the transmembrane region to improve solubility and secretion. These antigens are formulated with adjuvants to induce both polyfunctional CD4+ T-cell responses and high titers of neutralizing antibodies. The therapeutic goal of targeting these antigens is to enhance the host's ability to suppress viral reactivation from latency in the sacral ganglia, thereby reducing clinical lesion frequency and subclinical viral shedding (Van Wagoner et al., 2018, PLOS ONE). Clinical trials have demonstrated that immunization with these antigens can lead to a significant reduction in the rate of viral shedding and the number of days with genital lesions. While GEN-003 development was discontinued by Genocea, these antigens remain significant targets in the field of HSV-2 immunotherapy research.

Other names

ICP4.2gD2ΔTMRGEN-003 antigensInfected cell protein 4Glycoprotein D-2HSV-2 antigens

Induction of antigen-specific T-cell and B-cell immune responses to suppress viral reactivation and entry.