# A novel prophylactic and therapeutic vaccine for ocular herpes simplex virus infections

> **NIH NIH R43** · RATIONAL VACCINES, INC. · 2022 · $269,616

## Abstract

SUMMARY: Herpes simplex virus (HSV-1) is a neurotropic alphaherpesvirus and a major cause of ocular
disease that can lead to blindness worldwide. The virus infects the corneal epithelium and subsequently
establishes latency in sensory neurons of the trigeminal ganglia (TG). Recurrent reactivation of the virus
causes shedding of virions in tears and herpetic stromal keratitis (HSK) that can lead to irreparable cornea
damage and loss of vision. Vaccination with a safe, live- attenuated virus could induce robust humoral and
cellular immune responses as it has been shown with other viruses including varicella zoster virus, which
also belongs to the alphaherpesvirus subfamily. A major roadblock in the use of HSV-1, as a live-attenuated
vaccine approach is that these viruses remain competent for infection of neurons and establishment of
latency. Rational Vaccines, Inc has acquired the rights to the VC2 live-attenuated HSV-1 vaccine strain.
VC2 is derived from HSV-1(F) and carries deletions in the amino termini of glycoprotein K (gK) and UL20,
both of which bind glycoprotein B (gB). These mutations allow the virus to replicate efficiently in cell culture;
however, the virus cannot enter into the axonal endings and establish latency in TG neurons after ocular
infection of mouse eyes. Intramuscular vaccination with the VC2 virus produces robust humoral and cellular
immune responses in mice and guinea pigs, and impressive protection against lethal intravaginal challenge
with either HSV-1(McKrae) or HSV-2(G) wild-type viruses in both mouse and guinea pig models, as well
as against ocular infection of mice. To explore the potential of VC2 as a vaccine approach for the prevention
and treatment of ocular herpes infection, we propose a detailed vaccination study in rabbits because rabbits
allow for the testing of VC2 as both a prophylactic and therapeutic vaccine. Our hypothesis is that
intramuscular vaccination with the VC2 virus will generate significant immune responses to protect rabbits
challenged with HSV-1 (McKrae) via the ocular route and prevent the establishment of latent viral genomes
in TG neurons. In addition, therapeutic vaccination with VC2 will significantly reduce viral shedding and
concomitant ocular virus-associated immunopathogenesis. Therapeutic intervention of recurrent ocular
HSV-1 disease would be of great clinical significance. Positive results from the proposed experiments will
pave the way for phase I clinical studies in humans.

## Key facts

- **NIH application ID:** 10482237
- **Project number:** 1R43AI165060-01A1
- **Recipient organization:** RATIONAL VACCINES, INC.
- **Principal Investigator:** Edward Gershburg
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $269,616
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10482237

## Citation

> US National Institutes of Health, RePORTER application 10482237, A novel prophylactic and therapeutic vaccine for ocular herpes simplex virus infections (1R43AI165060-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10482237. Licensed CC0.

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