A novel prophylactic and therapeutic vaccine for ocular herpes simplex virus infections
Ended Project Grant Awarded Last action
- Award ID
- R43AI165060
- Recipient
-
Rational Vaccines Inc. UEI PKJWJVTMUS63
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $536,203
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date
- Originally
- Place of performance
- Massachusetts, USA
Award details come from USAspending.gov.
Description
- Abstract
- 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.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | -$3,029 | |
| Amendment | $0 | |
| Amendment | $269,616 | |
| Original award | $269,616 |
Quick answers
Who received award R43AI165060?
R43AI165060 was awarded to Rational Vaccines Inc. by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on September 1, 2022.
How much is award R43AI165060 worth?
$536,203 has been obligated on R43AI165060.
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