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:
- 金额:$ 26.96万
- 依托单位:
- 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:
- 关键词:AdultAfferent NeuronsAntiviral AgentsAttenuatedAttenuated VaccinesAxonBindingBiological ModelsBlindnessCaviaCell Culture TechniquesChildClinical ResearchCorneaDermalDiseaseElectric StimulationEpinephrineEyeEye InfectionsEye diseasesGlycoproteinsHerpes Simplex Virus VaccinesHerpesviridae InfectionsHerpesvirus Type 3Herpetic KeratitisHumanHuman Herpesvirus 2ImmuneImmune responseImmunologicsImmunotherapyInfectionInflammationIntramuscularInvestigationIontophoresisKeratitisLeadLesionMechanical StimulationMediatingModelingMusMutationNerve Growth FactorsNeuronsNicotineOryctolagus cuniculusOutcomePathogenesisPhasePreventionPrevention approachPreventive vaccineProductionRadial KeratotomyRecurrenceRightsRouteSCID MiceSafetySalivaSimplexvirusStimulusStructure of trigeminal ganglionTestingTherapeutic InterventionTherapeutic UsesTissuesVaccinationVaccine TherapyVaccinesViralViral GenomeVirionVirusVirus DiseasesVirus LatencyVirus Sheddingclinically significantcorneal epitheliumexperimental studyguinea pig modelhuman diseaseimmunopathologyneuronal cell bodyneurotropicnovelpreventprophylacticreactivation from latencytherapeutic vaccinevaccine 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
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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Edward Gershburg其他文献
Edward Gershburg的其他文献
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{{ truncateString('Edward Gershburg', 18)}}的其他基金
Preclinical Evaluation of a Novel Immunomodulatory Vaccine for Preventing and Treating HSV Infections
预防和治疗 HSV 感染的新型免疫调节疫苗的临床前评价
- 批准号:
10600886 - 财政年份:2023
- 资助金额:
$ 26.96万 - 项目类别:
Definition of structural organization and enzymology of the EBV protein kinase.
EBV 蛋白激酶的结构组织和酶学的定义。
- 批准号:
7916959 - 财政年份:2009
- 资助金额:
$ 26.96万 - 项目类别:
Definition of structural organization and enzymology of the EBV protein kinase.
EBV 蛋白激酶的结构组织和酶学的定义。
- 批准号:
7878932 - 财政年份:2009
- 资助金额:
$ 26.96万 - 项目类别:
Definition of structural organization and enzymology of the EBV protein kinase.
EBV 蛋白激酶的结构组织和酶学的定义。
- 批准号:
7636886 - 财政年份:2008
- 资助金额:
$ 26.96万 - 项目类别:
Definition of structural organization and enzymology of the EBV protein kinase.
EBV 蛋白激酶的结构组织和酶学的定义。
- 批准号:
7472146 - 财政年份:2008
- 资助金额:
$ 26.96万 - 项目类别:
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