Measurement of Antibody Epitope Signatures by Peptide Microarrays to Determine Recency of HIV Infection

通过肽微阵列测量抗体表位特征来确定 HIV 感染的新近程度

基本信息

项目摘要

 DESCRIPTION (provided by applicant): There is a critical need in HIV research to develop a rapid, inexpensive, and accurate assay that can be used to estimate HIV incidence anywhere in the world and on any sample. In the absence of such a test, it is challenging to identify high risk populations, model transmission, and monitor the outcome of public health interventions. Our long term goal is to develop new methods to measure HIV incidence to improve HIV epidemiology in resource-poor settings. The overall objective of the proposed research is to use a cutting-edge immunologic assay, the global HIV-1 peptide microarray, to define the key epitope signatures of HIV-specific antibodies associated with different stages of HIV infection. Our central hypothesis is that the greater the duration of HIV infection, the greater the diversity of HIV-specific antibodies. The rationale for the proposed research is that, once it is known that antibody epitope signatures are associated with different stages of HIV infection, then the global HIV-1 peptide microarray can be further developed as a tool to measure HIV incidence. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) to identify the key epitope signatures of HIV-specific antibodies that are associated with three different stages of HIV infection (recent, chronic viremia, and ART suppression); and 2) to determine how HIV serologic diversity is associated with increasing HIV viral diversity in viremic subjects over time. Under the first aim, we will perform antibody epitope mapping with a global HIV-1 peptide microarray on individuals with known time since infection. We will complement the peptide microarray with established incidence assays to measure antibody magnitude and avidity. When the proposed studies have been completed, it is our expectation that the breadth of antibody epitope signatures will be significantly increased in non-recent HIV stages compared to in recent HIV infection. Under the second aim, we will determine the relationship between diversity of HIV epitope- specific antibody responses (as measured by peptide microarray) and HIV viral diversity (as measured by single genome amplification and Sanger sequencing) to provide a better pathogenic understanding of antibody evolution and how it relates to HIV incidence. When these studies have been completed, it is our expectation that the depth of antibody binding (# sequence variants recognized at any given binding site) will be positively associated with increasing HIV viral diversity measures over time. The research proposed in this application is innovative, in our opinion, because it introduces a novel high-throughput antibody-based assay that has the potential to be as sensitive and specific for recent HIV infection as a viral diversity assay. The proposed research is significant, because it is expected to be the demonstration that antibody epitope specificity - as measured by the diversity of antibody binding to HIV peptides - can serve as a biomarker of different stages of HIV infection. Ultimately, such knowledge will inform the design of novel HIV incidence assays that will have broad importance in the fields of HIV epidemiology and diagnostics.


项目成果

期刊论文数量(0)
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Timothy Jensen Henrich其他文献

Timothy Jensen Henrich的其他文献

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{{ truncateString('Timothy Jensen Henrich', 18)}}的其他基金

Mentoring Scientists for Careers in HIV Translational Clinical Research
指导科学家从事艾滋病毒转化临床研究
  • 批准号:
    10762827
  • 财政年份:
    2023
  • 资助金额:
    $ 22.51万
  • 项目类别:
HIV Reservoir and Gene Modified Cell Dynamics Following Autologous Stem Cell Transplantation
自体干细胞移植后的 HIV 储库和基因修饰细胞动力学
  • 批准号:
    10700521
  • 财政年份:
    2023
  • 资助金额:
    $ 22.51万
  • 项目类别:
In situ and digital spatial profiling of the active HIV reservoir in autopsy-derived tissues
尸检组织中活性 HIV 储存库的原位和数字空间分析
  • 批准号:
    10459933
  • 财政年份:
    2022
  • 资助金额:
    $ 22.51万
  • 项目类别:
In situ and digital spatial profiling of the active HIV reservoir in autopsy-derived tissues
尸检组织中活性 HIV 储存库的原位和数字空间分析
  • 批准号:
    10614019
  • 财政年份:
    2022
  • 资助金额:
    $ 22.51万
  • 项目类别:
In Vivo PET Imaging of HIV Infection
HIV 感染的体内 PET 成像
  • 批准号:
    10237379
  • 财政年份:
    2020
  • 资助金额:
    $ 22.51万
  • 项目类别:
In Vivo PET Imaging of HIV Infection
HIV 感染的体内 PET 成像
  • 批准号:
    10095057
  • 财政年份:
    2020
  • 资助金额:
    $ 22.51万
  • 项目类别:
In Vivo PET Imaging of HIV Infection
HIV 感染的体内 PET 成像
  • 批准号:
    10453617
  • 财政年份:
    2020
  • 资助金额:
    $ 22.51万
  • 项目类别:
Targeting Non Viral Markers of HIV Persistence
针对艾滋病毒持续存在的非病毒标志物
  • 批准号:
    10392921
  • 财政年份:
    2018
  • 资助金额:
    $ 22.51万
  • 项目类别:
Longitudinal Immunological Impact of SARS-CoV-2 Infection
SARS-CoV-2 感染的纵向免疫学影响
  • 批准号:
    10265644
  • 财政年份:
    2018
  • 资助金额:
    $ 22.51万
  • 项目类别:
Targeting Non Viral Markers of HIV Persistence
针对 HIV 持续存在的非病毒标志物
  • 批准号:
    9906848
  • 财政年份:
    2018
  • 资助金额:
    $ 22.51万
  • 项目类别:

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