GORILLA ADENOVIRUS ZIKA VACCINE FOR HUMANS
人类大猩猩腺病毒寨卡疫苗
基本信息
- 批准号:9316943
- 负责人:
- 金额:$ 19.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-03-20 至 2019-02-28
- 项目状态:已结题
- 来源:
- 关键词:Adenovirus VectorAdenovirusesAdultAmericasAnimal ModelAntibodiesAntigensAntiviral AgentsApplications GrantsArbovirusesArthropodsAttenuatedB-LymphocytesBindingBypassCancer VaccinesCapsidCellsCellular ImmunityClinicalClinical TrialsCommunicable DiseasesCongenital AbnormalityCountryDendritic CellsDengueDiamondDiseaseDisease OutbreaksEngineeringEpidemicEpidemiologyEvaluationFamilyFemaleFiberFlavivirusGenerationsGeneticGoalsGorilla gorillaGuillain-Barré SyndromeHealthHumanHumoral ImmunitiesImmuneImmune TargetingImmune responseImmunityInfectionLaboratoriesLigand BindingMaternal-Fetal TransmissionMeasuresMethodologyMethodsMicrocephalyModelingModificationMusMyelogenousNeurologicOutcomePan GenusPreclinical TestingPreventive vaccinePublic HealthReagentReceptor CellReportingSimian AdenovirusesSpontaneous abortionSystemTechnologyTeratogensTestingTranslationsTropismVaccinationVaccinesViralViral AntigensViral ProteinsVirusVirus DiseasesWorld Health OrganizationYellow fever virusZika VirusZika virus vaccineadaptive immune responsebasecancer cellcell envelopecell typechikungunyaclinical translationcost effectivedesigndisorder controleffective interventionenv Gene Productsfetalimmunogenicityimprovedin vivomouse modelnovelparticleprotective efficacypublic health emergencyreceptortransmission processvaccine candidatevaccine developmentvaccine responsevectorvector vaccinevector-based vaccineviral transmissionvirus envelopevirus pathogenesis
项目摘要
Zika virus (ZIKV) is an arthropod-borne flavivirus that has spread rapidly across the Americas with 35
countries and territories reporting active viral transmission over the past year; this epidemic has
prompted the WHO to declare ZIKV a worldwide public health emergency. An effective vaccine for
ZIKV would be a cost-effective intervention that limits clinical disease and controls the spread of the
infection since there is no antiviral treatment available. The goal of this proposal is to design novel
ZIKV vaccine candidates and conduct initial preclinical testing in newly-generated mouse
models of infection and disease. In this regard, vector-based vaccine systems offer key advantages
including their robust efficiency to elicit humoral and cellular immunity by mimicking infection while
producing ZIKV antigens de novo. Adenovirus (Ad) vectors have emerged as one of the most promising
vaccine platforms that stimulate both innate and adaptive immune responses, and have been evaluated
extensively in clinical trials in the cancer vaccine and infectious disease fields. The use of simian Ad
species isolated from chimpanzee and gorilla offers a unique ability to bypass pre-existing immunity to
human Ad. Here, we will test whether gorilla-based Ad (GAd) vectors expressing soluble envelope (E)
protein or intact subviral particles (SVPs) can elicit neutralizing humoral and cellular immune responses
and protect against ZIKV infection and disease. Furthermore, we hypothesize that targeting GAd
vectors specifically to dendritic cells (DCs) will facilitate direct presentation of ZIKV structural
antigens and improve vaccination outcome compared to conventional Ad-based vaccine. To test
our hypothesis we have developed methods to ablate native Ad tropism via genetic modifications of the
viral capsid while allowing recognition of the target cell receptor and the possibility of cell-specific
delivery in vivo. We showed the utility of incorporating single domain antibody (sdAb) species into viral
particles for Ad targeting to cancer cell types and immature myeloid murine DCs. We propose to use
GAd developed by our commercial partner GenVec, Inc., as this vector platform has greater potential
for clinical translation. In support of this study, we generated a panel of sdAb candidates that bind to the
DC-specific receptor Clec9A that can be exploited to induce robust T- and B-cell immune responses
following vaccination. The Diamond laboratory has developed new murine models of ZIKV
pathogenesis including a model of maternal-fetal transmission. These models will allow us to assess
rapidly the efficacy of our different candidate vaccines. In summary, our collaborative group has the
necessary reagents, technology, and expertise to develop and evaluate novel GAd-vectored ZIKV
vaccine candidates using relevant animal models. We believe the translation of these results could
have a significant impact on reducing ZIKV disease and spread, a beneficial effect on human health.
寨卡病毒(ZIKV)是一种节肢动物传播的黄病毒,已在美洲迅速传播
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)
专利数量(0)
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David Terry Curiel其他文献
David Terry Curiel的其他文献
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{{ truncateString('David Terry Curiel', 18)}}的其他基金
A Novel Vector Platform to Actualize T Cell Modification In Vivo
一种在体内实现 T 细胞修饰的新型载体平台
- 批准号:
10663022 - 财政年份:2023
- 资助金额:
$ 19.06万 - 项目类别:
Endothelial-targeted adenovirus for organ-selective gene editing in vivo
用于体内器官选择性基因编辑的内皮靶向腺病毒
- 批准号:
10228031 - 财政年份:2019
- 资助金额:
$ 19.06万 - 项目类别:
Endothelial-targeted adenovirus for organ-selective gene editing in vivo
用于体内器官选择性基因编辑的内皮靶向腺病毒
- 批准号:
9810634 - 财政年份:2019
- 资助金额:
$ 19.06万 - 项目类别:
A 3D IN VITRO DISEASE MODEL OF ATRIAL CONDUCTION
心房传导 3D 体外疾病模型
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10166441 - 财政年份:2017
- 资助金额:
$ 19.06万 - 项目类别:
A 3D IN VITRO DISEASE MODEL OF ATRIAL CONDUCTION
心房传导 3D 体外疾病模型
- 批准号:
10228624 - 财政年份:2017
- 资助金额:
$ 19.06万 - 项目类别:
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