Markers of Viral Set Point in Primary HIV-1C Infection
原发性 HIV-1C 感染的病毒设定点标志物
基本信息
- 批准号:7422344
- 负责人:
- 金额:$ 43.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-05-01 至 2010-04-30
- 项目状态:已结题
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAcuteAreaBotswanaCCR5 geneCD8B1 geneCXCR4 geneChronicContainmentCoupledDNAEpidemicEvolutionGaggingHIV InfectionsHIV vaccineHIV-1Immune responseImmunologic MarkersImmunologicsInfectionKineticsMacrophage Inflammatory ProteinsModelingMonitorMonkeysPatternPhenotypePhylogenetic AnalysisPlasmaProductionProspective StudiesRANTESRNAResearchRiskSmall Inducible Cytokine A3StagingStudy SubjectT-LymphocyteT-Lymphocyte SubsetsTestingTimeVaccine DesignViralViral GenesViral Load resultViral MarkersVirusbasebeta-Chemokinesdesignresearch studyresponsevaccine developmentviral DNAvirus host interaction
项目摘要
DESCRIPTION (provided by applicant): Most HIV vaccine designs are currently based on studies of chronic HIV-1 subtype B infection. However, the prevailing dominance of HIV-1 subtype C (HIV-1 C) in the worldwide AIDS epidemic, and the efficient, albeit temporary, containment of the virus during acute HIV infection necessitates a comprehensive analysis of primary HIV-1 C infection with regard to vaccine design. Assuming that the level of viral set point is dictated by virus-host interactions, we postulated that (i) the kinetics of viral replication, viral diversity, and immune responses vary between primary HIV-1 infections; (ii) virological and immunological determinants in acute HIV-1 infection are related to viral set point, and (iii) virological and immunological parameters in acute HIV-1 infection associated with low viral set point could be identified and targeted for vaccine development. We hypothesize that a combination of functional Gag p24-specific T cell responses and low viral diversity within tat and nef in primary HIV-1 C infection is associated with low viral set point, while lack of functional p24-specific immune response coupled with high tat and nef diversity are markers of high viral set point. To test this hypothesis a prospective study on acute and early HIV-1 infection in Botswana has been designed. There are two Specific Aims in the study: 1. To characterize the magnitude, breadth and kinetics of virological and immunological determinants during primary HIV-1 C infection including transient changes in viral evolution and immune responses. Viral load (RNA and DNA), viral diversity (p24, tat, env, and nef), virus-specific CD4+ and CD8+ T cell immune responses, expression of CCR5 and CXCR4, and levels of beta-chemokine production (MIP-1a, MIP-1B and RANTES) will be analyzed. 2. To assess the association between virological and immunological markers in primary HIV-1 C infection with viral set point. To develop a multivariate model of the inter-relationship of these factors with viral set point.
描述(由申请方提供):目前大多数HIV疫苗设计是基于慢性HIV-1亚型B感染的研究。然而,HIV-1亚型C(HIV-1 C)在世界范围内的艾滋病流行中占主导地位,以及在急性HIV感染期间对病毒的有效(尽管是暂时的)遏制,需要对原发性HIV-1 C感染的疫苗设计进行全面分析。假设病毒设定点的水平由病毒-宿主相互作用决定,我们假设(i)病毒复制的动力学、病毒多样性和免疫应答在原发性HIV-1感染之间变化;(ii)急性HIV-1感染中的病毒学和免疫决定因素与病毒设定点有关,和(iii)与低病毒设定点相关的急性HIV-1感染中的病毒学和免疫学参数可以被识别并作为疫苗开发的目标。我们假设,在原发性HIV-1C感染中,功能性Gag p24特异性T细胞应答和达特和nef内的低病毒多样性的组合与低病毒设定点相关,而缺乏功能性p24特异性免疫应答加上高达特和nef多样性是高病毒设定点的标志。为了检验这一假设,在博茨瓦纳的急性和早期HIV-1感染的前瞻性研究已经设计。本研究有两个具体目的:1.描述原发性HIV-1 C感染期间病毒学和免疫学决定因素的幅度、广度和动力学,包括病毒进化和免疫应答的短暂变化。将分析病毒载量(RNA和DNA)、病毒多样性(p24、达特、env和nef)、病毒特异性CD 4+和CD 8 + T细胞免疫应答、CCR 5和CXCR 4的表达以及β-趋化因子产生水平(MIP-1a、MIP-1B和RANTES)。2.评估原发性HIV-1C感染者的病毒学和免疫学标志物与病毒设定点之间的关系。开发这些因素与病毒设定点之间相互关系的多变量模型。
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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VLADIMIR A NOVITSKY其他文献
VLADIMIR A NOVITSKY的其他文献
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{{ truncateString('VLADIMIR A NOVITSKY', 18)}}的其他基金
Pilot Study to Monitor HIV Cluster Dynamics and Active HIV sub-Epidemics in Real Time
实时监测艾滋病毒集群动态和活跃艾滋病毒亚流行病的试点研究
- 批准号:
9560096 - 财政年份:2018
- 资助金额:
$ 43.07万 - 项目类别:
Mutational pathways in early HIV infection: novel guide to immunologic analyses
早期 HIV 感染的突变途径:免疫学分析新指南
- 批准号:
7927933 - 财政年份:2010
- 资助金额:
$ 43.07万 - 项目类别:
Mutational pathways in early HIV infection: novel guide to immunologic analyses
早期 HIV 感染的突变途径:免疫学分析新指南
- 批准号:
8071640 - 财政年份:2010
- 资助金额:
$ 43.07万 - 项目类别:
Markers of Viral Set Point in Primary HIV-1C Infection
原发性 HIV-1C 感染的病毒设定点标志物
- 批准号:
7050550 - 财政年份:2005
- 资助金额:
$ 43.07万 - 项目类别:
Markers of Viral Set Point in Primary HIV-1C Infection
原发性 HIV-1C 感染的病毒设定点标志物
- 批准号:
7624663 - 财政年份:2005
- 资助金额:
$ 43.07万 - 项目类别:
Markers of Viral Set Point in Primary HIV-1C Infection
原发性 HIV-1C 感染的病毒设定点标志物
- 批准号:
7230930 - 财政年份:2005
- 资助金额:
$ 43.07万 - 项目类别:
Markers of Viral Set Point in Primary HIV-1C Infection
原发性 HIV-1C 感染的病毒设定点标志物
- 批准号:
6892244 - 财政年份:2005
- 资助金额:
$ 43.07万 - 项目类别:
Early and acute HIV-1 subtype C infection in Botswana
博茨瓦纳的早期急性 HIV-1 C 亚型感染
- 批准号:
6654657 - 财政年份:2003
- 资助金额:
$ 43.07万 - 项目类别:
Early and acute HIV-1 subtype C infection in Botswana
博茨瓦纳的早期急性 HIV-1 C 亚型感染
- 批准号:
6765109 - 财政年份:2003
- 资助金额:
$ 43.07万 - 项目类别:
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