Herpevac (gD2 subunit, GSK)
Also known as: gD-Alum/MPL, Herpevac Trial for Women
discontinued GlaxoSmithKline
Last updated:
| Developer | GlaxoSmithKline |
|---|---|
| Platform | protein subunit |
| HSV target | HSV-2 |
| Approach | prophylactic |
| Phase | discontinued |
| Status | Completed Phase 3 (the 'Herpevac Trial for Women', ~8,300 participants). It did not prevent HSV-2 genital disease, though it unexpectedly showed ~58% efficacy against HSV-1 genital disease. The program was not advanced. |
| Trials | NCT00057330 |
A prophylactic protein-subunit vaccine from GlaxoSmithKline built around HSV-2 glycoprotein D. In a large Phase 3 trial published in 2012, it failed to prevent genital disease caused by HSV-2 — its intended target — but unexpectedly reduced HSV-1 genital disease by about 58%. This HSV-1 versus HSV-2 split became an influential lesson in the field. The program was not taken further.
What it is
Herpevac was a prophylactic (preventive) protein-subunit vaccine developed by GlaxoSmithKline. It was built around a single HSV-2 protein — glycoprotein D (gD2) — combined with two adjuvants, alum and MPL. The idea was that antibodies against gD2 would stop the virus from entering cells and thereby prevent genital herpes.
Where it stands
Herpevac was tested in a large Phase 3 trial, the “Herpevac Trial for Women” (NCT00057330), enrolling about 8,300 women who were seronegative for both HSV-1 and HSV-2. The results, published in the New England Journal of Medicine in 2012, were pivotal — and instructive about the distinctions this site emphasizes:
- Against HSV-2 genital disease — the vaccine’s actual target — it was not effective (about 20% efficacy, not statistically significant).
- Against HSV-1 genital disease it was unexpectedly protective, with roughly 58% efficacy.
Later laboratory work suggested why: HSV-2’s gC2 and gE2 proteins blunt the antibody response that gD2 alone provokes, whereas HSV-1’s equivalents do not. This helped motivate the multi-protein (trivalent) designs that came after. GSK did not advance Herpevac, so the program is inactive. It stands as evidence that a vaccine can succeed against one herpes type while failing against another — which is exactly why HSV-1 and HSV-2 must never be treated as interchangeable.
Registry snapshot
HerpeVac Trial for Young Women
- Registry status
- Completed
- Phase
- phase 3
- Enrollment
- 8,323 (actual)
- Lead sponsor
- GlaxoSmithKline
- Started
- Jan 14, 2003
- Primary completion
- Aug 22, 2009
Registry record last updated Aug 27, 2018.
Background
- HSV-1 vs HSV-2: what's the difference?
Herpes simplex virus comes in two types. HSV-1 has traditionally caused oral herpes and HSV-2 genital herpes, but that line has blurred, and either type can infect either site. The distinction still matters for vaccines: a vaccine can protect against one type and not the other, as the Phase 3 Herpevac trial showed. Neither type has an approved vaccine as of 2026.
- Prophylactic vs therapeutic: two very different herpes vaccines
"A herpes vaccine" can mean two different things. A prophylactic (preventive) vaccine is given to people who are not infected, to stop them getting herpes simplex virus (HSV) at all. A therapeutic vaccine is given to people who are already infected, to reduce outbreaks and viral shedding. The two use different trials, endpoints, and populations — so the first question to ask of any candidate is which goal it targets. Neither type is approved.
- What each clinical trial phase does and doesn't prove
A plain-language guide to reading herpes (HSV) vaccine news by trial phase. Each phase answers a different question, and early-phase results say nothing about whether a vaccine prevents disease. A trial existing or finishing is not the same as a vaccine working — the Phase 3 Herpevac trial ran to completion but missed its main goal, and as of 2026 no HSV vaccine has cleared Phase 3 to approval.
- Why gC2, gD2, and gE2? The trivalent vaccine rationale
Several leading HSV-2 vaccine candidates combine three viral surface proteins — gC2, gD2, and gE2 — to do two jobs at once: block the virus from entering cells and disable two of the tricks it uses to evade the immune system. The rationale is well supported by animal data; whether it protects people is still being tested in an early-stage (Phase 1) human trial of the candidate BNT163.
- Why is HSV so hard to vaccinate against?
Herpes simplex virus establishes a lifelong dormant infection in nerve cells and carries genes that actively blunt the immune response, so even natural infection does not stop reinfection or recurrences — a vaccine has to outperform what the body manages on its own. This explainer walks through the four obstacles researchers keep hitting: latency, active immune evasion, unknown correlates of protection, and animal models that do not fully mirror human disease. As of 2026, no HSV vaccine is approved.
Sources
- Efficacy Results of a Trial of a Herpes Simplex Vaccine (Belshe et al.)
- Phase III Study to Assess the Prophylactic Efficacy and Safety of gD-Alum/MPL Vaccine in Young Women Seronegative for HSV-1 and HSV-2 (NCT00057330)
- Blocking HSV-2 Glycoprotein E Immune Evasion as an Approach To Enhance Efficacy of a Subunit Antigen Vaccine for Genital Herpes