Breadth and Functional Assessment of "Toggle"-Peptide-specific T Cell Responses
“切换”肽特异性 T 细胞反应的广度和功能评估
基本信息
- 批准号:7426244
- 负责人:
- 金额:$ 47.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-06-01 至 2008-07-31
- 项目状态:已结题
- 来源:
- 关键词:Amino Acid SequenceAmino Acid SubstitutionAmino AcidsAntigensArginineAutologousBase SequenceCD4 Positive T LymphocytesCell physiologyCharacteristicsClassConsensusDataDatabasesDetectionDevelopmentEpitopesExperimental DesignsFrequenciesFutureGaggingHIVHIV InfectionsHIV vaccineHelper-Inducer T-LymphocyteImmuneImmune TargetingImmune responseIn VitroIndividualLysineMinorNatureNucleotidesNumbersOutcomePatternPeptide LibraryPeptide Sequence DeterminationPeptidesPopulationPositioning AttributePropertyProteinsSequence AnalysisT-LymphocyteT-Lymphocyte EpitopesTestingVaccine DesignVaccinesValineVariantViralViral ProteinsVirusWorkbasecohortconceptcopingcostcross reactivitycytotoxicdesigndisorder controlimmunogenicityimprovedpol genesreagent testingresponse
项目摘要
HIV sequence diversity is a major hurdle for the development of an HIV vaccine and severely impacts the
ability to detect ex vivo immune responses in HIV infected individuals. Different approaches have been
suggested to cope with this issue, but have not always been effective in overcoming the discrepancy
between infecting viral sequence and in vitro antigen test sets. As a consequence, most immune analyses
to date provide limited information on the immunogenicity of sequence variants that could represent valuable
candidates for HIV vaccine design. In addition, most past efforts defining immune correlates of controlled
HIV infection have been similarly limited in their inclusion of sequence diversity, questioning whether all of
the phenotypic and functional characteristics of reportedly protective responses would extend to variant
sequences. The use of "toggled" peptides, representing essentially small peptide libraries with limited
diversity, has the potential to overcome a number of these problems, providing important guidance for
antigen selection and sequence variant inclusion in future vaccine immunogens.
Aside from detecting significantly more and stronger HIV-specific immune responses, sequence variants that
are present in the toggled peptides may induce quantitatively and qualitatively different immune responses,
for both CD4 as well as CDS T cells, providing the basis to more comprehensively define potential immune
correlates of controlled HIV infection. Based on extensive preliminary data showing the superiority of
toggled peptides to elicit T cell responses compared to different single sequence (e.g. consensus) test
reagents, the present application aims in a first step to define the level of sequence diversity coverage that
provides optimal detection of HIV-specific responses in a cohort of HIV clade B infected individuals with
varying disease control. Subsequently, toggled peptides are investigated for their ability to stimulate recall
responses with different functional and phenotypic patterns, identifying sequence variants with improved
immunogenicity and associated with polyfunctional responses. The frequency of these sequence variants in
the HIV database and the preferential detection of specific polyfunctional response patterns in HIV
controllers will be investigated to support rational sequence variant selection for inclusion in vaccine
candidates.
Overall, the proposed studies will provide urgently needed information on the impact of sequence diversity
on the functional properties of virus-specific CD4 and CDS T cells, and together with an assessment of the
potential for T cell responses to cross-react between different viral isolates or clades, the analyses will
support the further design of HIV vaccines immunogens that can induce broad, strong and self-renewing T
cell responses with wide cross-reactivity potential.
HIV序列多样性是开发HIV疫苗的主要障碍,并严重影响了HIV疫苗的生物学特性。
检测HIV感染个体中的离体免疫应答的能力。不同的方法已经
建议科普这一问题,但并不总是有效地克服差异,
感染病毒序列和体外抗原测试集之间的关系。因此,大多数免疫分析
迄今为止提供的关于序列变体免疫原性的信息有限,
HIV疫苗设计的候选人。此外,大多数过去的努力定义免疫相关的控制,
HIV感染在其包含的序列多样性方面也受到类似的限制,质疑是否所有的序列多样性都是有限的。
所报道保护性应答的表型和功能特征将延伸到变体
序列的使用“切换的”肽,代表基本上小的肽文库,
多样性,有可能克服这些问题,提供重要的指导,
在未来疫苗免疫原中的抗原选择和序列变体包含。
除了检测到明显更多和更强的HIV特异性免疫反应外,
存在于切换的肽中可以在数量上和质量上诱导不同的免疫应答,
对于CD4和CD8 T细胞,为更全面地定义潜在的免疫功能提供了基础。
控制HIV感染的相关因素。基于大量的初步数据显示,
与不同的单一序列(例如共有序列)测试相比,切换肽以引发T细胞应答
为了使用这些试剂,本申请的第一步旨在定义序列多样性覆盖度的水平,
提供了HIV进化枝B感染个体队列中HIV特异性应答的最佳检测,
不同的疾病控制。随后,研究切换肽刺激回忆的能力
具有不同功能和表型模式的响应,鉴定具有改进的
免疫原性和与多功能反应相关。这些序列变异的频率
艾滋病毒数据库和优先检测艾滋病毒中的特定多功能反应模式
控制器将被调查,以支持合理的序列变异体的选择,包括在疫苗
候选人
总的来说,拟议的研究将提供迫切需要的信息的影响,序列多样性
关于病毒特异性CD 4和CDS T细胞的功能特性,以及对病毒特异性CD 4和CDS T细胞的功能特性的评估
T细胞应答在不同病毒分离株或进化枝之间交叉反应的可能性,分析将
支持进一步设计HIV疫苗免疫原,可以诱导广泛,强大和自我更新的T细胞,
具有广泛交叉反应潜力的细胞反应。
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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CHRISTIAN BRANDER其他文献
CHRISTIAN BRANDER的其他文献
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{{ truncateString('CHRISTIAN BRANDER', 18)}}的其他基金
Role of host factors and HLA-E T cell immunity in HIV rebound kinetics
宿主因素和 HLA-E T 细胞免疫在 HIV 反弹动力学中的作用
- 批准号:
10205968 - 财政年份:2017
- 资助金额:
$ 47.94万 - 项目类别:
Role of host factors and HLA-E T cell immunity in HIV rebound kinetics
宿主因素和 HLA-E T 细胞免疫在 HIV 反弹动力学中的作用
- 批准号:
9332147 - 财政年份:2017
- 资助金额:
$ 47.94万 - 项目类别:
Consequences of acute HIV infection on the EBV-specific immunity
急性 HIV 感染对 EBV 特异性免疫的影响
- 批准号:
8118769 - 财政年份:2007
- 资助金额:
$ 47.94万 - 项目类别:
Consequences of acute HIV infection on the EBV-specific immunity
急性 HIV 感染对 EBV 特异性免疫的影响
- 批准号:
7665422 - 财政年份:2007
- 资助金额:
$ 47.94万 - 项目类别:
Consequences of acute HIV infection on the EBV-specific immunity
急性 HIV 感染对 EBV 特异性免疫的影响
- 批准号:
7450101 - 财政年份:2007
- 资助金额:
$ 47.94万 - 项目类别:
Consequences of acute HIV infection on the EBV-specific immunity
急性 HIV 感染对 EBV 特异性免疫的影响
- 批准号:
8113502 - 财政年份:2007
- 资助金额:
$ 47.94万 - 项目类别:
Consequences of acute HIV infection on the EBV-specific immunity
急性 HIV 感染对 EBV 特异性免疫的影响
- 批准号:
7878524 - 财政年份:2007
- 资助金额:
$ 47.94万 - 项目类别:
Consequences of acute HIV infection on the EBV-specific immunity
急性 HIV 感染对 EBV 特异性免疫的影响
- 批准号:
7479325 - 财政年份:2007
- 资助金额:
$ 47.94万 - 项目类别:
Promiscuous presentation of HLA class I restricted, HIV derived CTL epitopes
HLA I 类限制性 HIV 衍生 CTL 表位的混杂呈现
- 批准号:
7006836 - 财政年份:2005
- 资助金额:
$ 47.94万 - 项目类别:
Promiscuous presentation of HLA class I restricted, HIV derived CTL epitopes
HLA I 类限制性 HIV 衍生 CTL 表位的混杂呈现
- 批准号:
7074644 - 财政年份:2005
- 资助金额:
$ 47.94万 - 项目类别:
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