# Nucleoside-modified mRNA vaccine for prevention and treatment of genital herpes

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $812,498

## Abstract

Abstract
 Genital herpes affects 650 million people globally. Vaccines are urgently needed to prevent infection and treat
individuals already infected. During the current funding cycle, we developed a candidate vaccine for preventing
genital herpes that uses nucleoside-modified mRNA encapsulated within lipid nanoparticles (LNP) to express
herpes simplex virus type 2 (HSV-2) glycoproteins C, D, and E (gC2, gD2, gE2). The vaccine targets an entry
molecule, gD2, and two immune evasion molecules, gC2 and gE2. Our vaccine candidate will enter phase 1
human trials in December 2022. Our new goals are to define the immune correlates of protection for the
trivalent vaccine using sera we collected from immunized mice and guinea pigs during this grant cycle, and to
develop an mRNA-based vaccine as immunotherapy.
 In Aim 1, we will define the immune correlates of protection. Our hypothesis is that by defining immune
correlates, we will better understand the mechanisms of vaccine protection and the immune responses required
for success in human trials. We will use high throughput biosensor technology and our extensive panel of gC2,
gD2, and gE2 monoclonal antibodies to determine whether the trivalent vaccine produces antibodies to crucial
epitopes on gC2, gD2 and gE2. The epitopes of interest include those on gC2 that bind complement component
C3b to inhibit complement activation, gE2 that bind the IgG Fc domain to block Fc-mediated activities including
complement activation and antibody-dependent cellular cytotoxicity, and gD2 that bind to cell receptors for virus
entry and mediate cell-to-cell spread. We will correlate antibody binding to these important epitopes with
protection against clinical outcomes including genital lesions and latent infection. The epitope mapping studies
will enable us to assess the contribution of each of the glycoprotein immunogens to protection.
 Aim 2 uses mRNA immunogens to develop a genital herpes therapeutic vaccine. We hypothesize that T cell
responses will be particularly important for a successful therapeutic vaccine. In Preliminary studies, we infected
guinea pigs intravaginally with HSV-2 and once recovered, we immunized with glycoproteins E and I (gE2/gI2)
mRNA-LNP. gE2/gI2 mRNA-LNP reduced the number of days with recurrent genital lesions by 47%, an excellent
start towards our primary endpoint of >70% reduction in recurrent genital lesions. To achieve our goal of >70%,
we will incorporate other antigens, including additional glycoproteins, immediate early, capsid and tegument
immunogens and assess CD4 and CD8 T cell responses in male and female mice. We will advance the best
candidates for efficacy studies in guinea pigs. We will focus initially on glycoprotein immunogens because of the
remarkable success of a therapeutic vaccine for a closely related virus, varicella zoster virus, that uses
glycoprotein E as the antigen. We will include the trivalent gC2/gD2/gE2 vaccine in the therapeutic studies to
determine whether ...

## Key facts

- **NIH application ID:** 10870168
- **Project number:** 5R01AI139618-06
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Harvey Michael Friedman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $812,498
- **Award type:** 5
- **Project period:** 2019-04-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870168

## Citation

> US National Institutes of Health, RePORTER application 10870168, Nucleoside-modified mRNA vaccine for prevention and treatment of genital herpes (5R01AI139618-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10870168. Licensed CC0.

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