Herpes vaccine candidate
Trivalent gC2/gD2/gE2 mRNA (UPenn)
Also known as: Friedman–Weissman trivalent, UPenn HSV-2 trivalent mRNA-LNP
preclinical University of Pennsylvania (Friedman & Weissman labs); licensed to BioNTech
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Trivalent gC2/gD2/gE2 mRNA (UPenn) is a prophylactic (preventive) mRNA vaccine candidate for HSV-2, developed by University of Pennsylvania. Development phase: preclinical, meaning laboratory and animal studies only; not yet tested in people. Mouse, guinea pig and primate studies only. Its clinical form is BioNTech's BNT163.
Page last updated .
| Developer | University of Pennsylvania (Friedman & Weissman labs); licensed to BioNTech |
|---|---|
| Platform | mRNA |
| HSV target | HSV-2 |
| Approach | prophylactic |
| Phase | preclinical |
| Status | Academic preclinical program. Strong protection in animal models (mice, guinea pigs, non-human primates). Its clinical development is BioNTech's BNT163, now in a Phase 1 trial. |
| Trials |
An academic mRNA vaccine from the University of Pennsylvania (Harvey Friedman and Drew Weissman) that targets three HSV-2 glycoproteins — gC2, gD2, and gE2. It has shown strong protection against genital herpes in animal models but has not itself been tested in a registered human trial. Penn licensed the technology to BioNTech, whose Phase 1 candidate BNT163 is the clinical form of this approach.
What the UPenn trivalent vaccine is
This is the academic research program behind much of the current mRNA herpes- vaccine effort. Developed at the University of Pennsylvania by the labs of Harvey Friedman and Drew Weissman (the latter a Nobel laureate for the mRNA work underlying COVID-19 vaccines), it is a trivalent mRNA vaccine: it encodes three HSV-2 surface proteins — glycoproteins gC2, gD2, and gE2. The design aims to block the virus from entering cells (via gD2) and to neutralize two of the ways HSV evades the immune system (via gC2 and gE2).
Where the UPenn trivalent vaccine stands
This program is preclinical — its published results come from animal studies (mice, guinea pigs, and non-human primates), not human trials. In those models it provided strong protection against genital disease, including reductions in subclinical viral shedding, and has been studied both to prevent infection and, in guinea pigs, to reduce recurrences in already-infected animals. Animal results, however promising, are not clinical results.
Two further mouse studies from the Friedman group appeared in 2026. One found that the gC2 component alone, given as mRNA, protected mice against vaginal HSV-2 challenge at every dose tested, and that antibodies blocking gC2’s interference with the complement system (part of the immune system) were the protective ones in a passive-transfer experiment. The other found that the full trivalent vaccine protected mice against HSV-1 eye infection, although some animals still had mild inflammation or traces of viral DNA afterward. Both are mouse data; neither says how the vaccine behaves in people. For background on how this platform works, see How mRNA herpes vaccines work.
The University of Pennsylvania licensed this trivalent technology to BioNTech; the author disclosures on the 2025 IDWeek abstract state that Friedman, Cohen and Awasthi are inventors on a patent Penn licensed to BioNTech, and the abstract describes BNT163 as a trivalent mRNA vaccine encoding gC2, gD2 and gE2. The registry record for BNT163’s trial (NCT05432583, sponsor BioNTech) does not itself name Penn or the three antigens, so that link rests on the abstract. Its clinical form is the candidate BNT163, which is in a Phase 1 trial. In other words, this entry and BNT163 are two stages of the same scientific lineage — the academic origin here, the in-human testing there — not two independent vaccines.
No human trial of this academic program is registered under the University of Pennsylvania as sponsor, as of a ClinicalTrials.gov search on 2026-10-21. The only registered human study of the trivalent vaccine is BioNTech’s, and the IDWeek 2025 abstract is a conference abstract, not a peer-reviewed paper: it reported that BNT163 was well tolerated in a blinded interim look and induced binding and neutralizing antibodies, with no efficacy data.
Background
- How mRNA herpes vaccines work
Several of the most-watched herpes vaccine candidates use mRNA — the same technology behind the COVID-19 vaccines. This explainer covers how an mRNA vaccine delivers instructions for a cell to make selected viral proteins, why several HSV programs chose the approach, and why a platform that works for one disease is not proof it will work for another.
- 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.
- 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.
Key literature
- HSV-2 gC2 mRNA immunization in mice protects by producing antibodies that bind immune evasion epitopes
- Immunogenicity and Efficacy of a Trivalent HSV-2 gC2, gD2, gE2 Nucleoside-Modified mRNA-LNP Vaccine Against HSV-1 Eye Infection and Neuroinvasion in Mice
- Safety and Immunogenicity of BNT163, a Trivalent mRNA HSV Vaccine Candidate for Genital Herpes
Sources
- Nucleoside-modified mRNA encoding HSV-2 glycoproteins C, D, and E prevents clinical and subclinical genital herpes
- Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models
- Safety and Immunogenicity of BNT163, a Trivalent mRNA HSV Vaccine Candidate for Genital Herpes (abstract P-105)
- A Clinical Trial in Healthy Volunteers and Volunteers With Recurrent Genital Herpes to Study the Safety, Tolerability, and Immune Responses After Vaccination With an Investigational Vaccine Designed to Prevent Genital Herpes Lesions (NCT05432583)
- HSV-2 gC2 mRNA immunization in mice protects by producing antibodies that bind immune evasion epitopes
- Immunogenicity and Efficacy of a Trivalent HSV-2 gC2, gD2, gE2 Nucleoside-Modified mRNA-LNP Vaccine Against HSV-1 Eye Infection and Neuroinvasion in Mice