Bio-Nanoparticles for HIV Antigen Delivery
Bio-Nanoparticles for HIV Antigen Delivery
批准号:
8653936
负责人:
OTTO O YANG
金额:
$19.25万
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-04-19 至 2015-03-31
关键词:
AIDS VaccinesAdenovirusesAmino Acid SequenceAnimal ModelAntigensAttenuatedAutologousBiologicalBiological AssayCD8B1 geneCellsCytoplasmCytotoxic T-LymphocytesDNADevelopmentDrug resistanceEukaryotic CellFaceFowlpoxGenerationsHIV AntigensHIV-1HistocompatibilityHumanImmuneImmune systemImmunityInfectionInfection preventionInterferonsLeftLifeMucous MembraneNegative StainingPathway interactionsPeptide Sequence DeterminationPeptidesPreventionPreventiveProtein SubunitsProteinsRNA SequencesRecombinantsRibonucleoproteinsRiskRomeSafetySerotypingStructureSubunit VaccinesTextThinkingToxic effectTransmission Electron MicroscopyUntranslated RNAVaccine DesignVaccinesVacciniaVacciniumViralViral ProteinsViremiaVirusWorkarmcarcinogenicityimmune activationimmunogenicimmunogenicitykillingsmemory CD4 T lymphocytenanoparticleneutralizing antibodynovel strategiesoptimismpublic health relevanceresponsesuccesstherapeutic vaccinevaccine candidatevectorvector vaccineviral resistance
中文摘要
描述(由申请方提供):有效的HIV-1疫苗可能需要CTL诱导成分。迄今为止,只有重组腺病毒-5疫苗是这种组分的候选者,但它面临着载体免疫的重大问题,并且具有未知的进入粘膜组织的能力。纳米颗粒作为疫苗载体提供了一些优势,但面临免疫原性、致癌性和制造质量的问题。
该提案探索了使用由自体人类蛋白质组成的生物纳米颗粒(“拱顶”),加载HIV-1序列作为疫苗。穹窿已被证明对CTL应答具有免疫原性并进入粘膜免疫系统。此外,它们由通常在细胞质中发现的自身蛋白组成,因此不应具有免疫原性或致癌性,并且易于以一致的质量生产。这两个目标是:
目的1:构建携带HIV-1保守蛋白序列的靶向库;
目的2:证实穹窿在全身和粘膜免疫区室中的免疫原性。
英文摘要
DESCRIPTION (provided by applicant): It is likely that a CTL-eliciting component will be required for an effective HIV-1 vaccine. To date, only the recombinant adenovirus-5 vaccine has been a candidate for such a component, but it faced significant issues with vector immunity and had unknown capacity to access mucosal tissues. Nanoparticles offer some advantages as vaccine vectors, but face problems with immunogenicity, carcinogenicity, and manufacturing quality.
This proposal explores the use of biological nanoparticles ("vaults") composed of autologous human proteins, loaded with HIV-1 sequences to serve as a vaccine. Vaults have been shown to be immunogenic for CTL responses and access the mucosal immune system. Additionally, they are composed of self-proteins that are normally found in the cytoplasm and therefore should not be immunogenic or carcinogenic, and are readily manufactured with consistent quality. The two aims will be:
Aim 1: To create targeted vaults carrying conserved HIV-1 protein sequences;
Aim 2: To confirm the immunogenicity of the vaults in systemic and mucosal immune compartments.
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会议论文
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Effects of Vaccine on Formation and Clearance of the HIV Latent Reservoir
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Functional Assessment of CTL Anergy in HIV Infection
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Dissection of HIV-1 CTL Escape Pathways
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资助金额:$38.5万
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财政年份:2014
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依托单位:
Dissection of HIV-1 CTL Escape Pathways
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依托单位:
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Identifying and closing gaps in TCR coverage of HIV-1 escape
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海外基金