权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

一种针对眼部单纯疱疹病毒感染的新型预防和治疗疫苗

基本信息

批准号：
10482237
负责人：
Edward Gershburg
金额：
$ 26.96万
依托单位：
RATIONAL VACCINES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10482237
关键词：
Adult Afferent Neurons Antiviral Agents Attenuated Attenuated Vaccines Axon Binding Biological Models Blindness Cavia Cell Culture Techniques Child Clinical Research Cornea Dermal Disease Electric Stimulation Epinephrine Eye Eye Infections Eye diseases Glycoproteins Herpes Simplex Virus Vaccines Herpesviridae Infections Herpesvirus Type 3 Herpetic Keratitis Human Human Herpesvirus 2 Immune Immune response Immunologics Immunotherapy Infection Inflammation Intramuscular Investigation Iontophoresis Keratitis Lead Lesion Mechanical Stimulation Mediating Modeling Mus Mutation Nerve Growth Factors Neurons Nicotine Oryctolagus cuniculus Outcome Pathogenesis Phase Prevention Prevention approach Preventive vaccine Production Radial Keratotomy Recurrence Rights Route SCID Mice Safety Saliva Simplexvirus Stimulus Structure of trigeminal ganglion Testing Therapeutic Intervention Therapeutic Uses Tissues Vaccination Vaccine Therapy Vaccines Viral Viral Genome Virion Virus Virus Diseases Virus Latency Virus Shedding clinically significant corneal epithelium experimental study guinea pig model human disease immunopathology neuronal cell body neurotropic novel prevent prophylactic reactivation from latency therapeutic vaccine vaccine trial

项目摘要

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.

摘要：单纯疱疹病毒（HSV-1）是一种嗜神经型α疱疹病毒，是眼部疾病的主要病因