gG-2 vaccine (EXCT4)

What it is

Glycoprotein G (gG-2) is a protein on the surface of HSV-2. Unlike the glycoproteins used in earlier HSV vaccines, it is specific to HSV-2: antibodies to it do not recognize HSV-1. The 2012 paper makes this point, noting that the cross-reactive glycoproteins B and D used in earlier human vaccine trials showed no protection against genital HSV-2 infection or disease. The Gothenburg groups’ vaccine is a recombinant (lab-made) protein version of gG-2 given with an adjuvant.

EXCT4 is a truncated, shortened form of the mature gG-2 protein. The 2021 paper says that, unlike the full mature form, it is secreted by the cells that make it, which allows it to be produced at scale more readily.

Where it stands

All published efficacy results are from mice. In 2012 the group reported that mice immunized with the mature gG-2 protein plus a CpG adjuvant had a 73% survival rate after a lethal vaginal HSV-2 challenge, against 20% for the protein alone and 0% for controls. A 2021 paper reports that EXCT4 with the adjuvant Advax-CpG protected mice from lethal genital challenge, with lower viral loads in vaginal washes, spinal cord and dorsal root ganglia (the clusters of nerve cells where HSV stays latent). A July 2026 paper reports that a recombinant gG-2 protein protected mice against genital challenge, that removing its sugar groups reduced the immune response and protection, and that a virus lacking the membrane-bound form spread poorly into nerve tissue.

The antibodies seen in these studies work differently from neutralizing antibodies, which block the virus from entering cells. In the 2012 mouse study, sera showed antibody-dependent cellular cytotoxicity (antibodies marking infected cells for killing by immune cells) and no neutralization. A 2024 paper reports the same pattern for gG-2 antibodies purified from people with HSV-2 infection.

The papers test vaccination before challenge, which is a prophylactic design, while the 2026 paper’s authors say the work supports both prophylactic and therapeutic vaccines, so this page lists the approach as unclear. A ClinicalTrials.gov search on 2026-10-21 found no record for EXCT4, for Simplexia or for a glycoprotein G HSV-2 vaccine. We found no primary source in hand for a company, a regulatory filing or a planned human trial, so none is stated here.

What this does and doesn’t mean

These are mouse results. They do not show that the vaccine would protect people, and the authors describe the 2021 findings as proof of concept for a candidate “warranting further investigation”. The sources here do not show that mouse survival or laboratory antibody activity predicts protection in people. No safety data in people exist for this candidate.