Susceptibility of antigen-specific CD4 T cells to HIV: implications for HIV vacci

抗原特异性 CD4 T 细胞对 HIV 的敏感性:对 HIV 疫苗的影响

基本信息

  • 批准号:
    8732199
  • 负责人:
  • 金额:
    $ 21.73万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-02-05 至 2016-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION: A central question to better understanding the pathogenesis of HIV infection is how memory CD4 T cells are infected and progressively depleted by HIV. Little is currently known about the impact of HIV infection on CD4 T cells of different pathogen or antigen specificities. Exploring this area is important for better understanding of the timing of different opportunistic infections in AIDS patients. In addition, identification of a functional population o vaccine-specific CD4 T cells that is "resistant" to HIV is critical for HIV vaccine design. We have established a novel system for studying the susceptibility of antigen-specific CD4 T cells to HIV, and have found that different antigen-specific CD4 T cells manifest marked differences in susceptibility to HIV infection. Our preliminary data show that compared to CD4 T cells specific to tetanus toxoid (TT) and Candida albicans (Candida), which are permissive to HIV, cytomegalovirus (CMV)-specific CD4 T cells are highly resistant to both R5 and X4 HIV with post-entry HIV restriction. Our microarray analysis identified a novel viral RNA sensor, IFIT1 that is highly upregulated in CMV-specific CD4 T cells. Of importance, in our ongoing experiments, we show that over-expression of IFIT1 inhibits HIV infection in A3R5 CD4 T cell line. Based on data already generated, we hypothesize that IFIT1 can inhibit HIV infection in human primary CD4 T cells and differential expression of IFIT1 regulates the permissiveness of antigen-specific CD4 T cells to HIV. We further propose to extend the novel system and observations to clinical HIV vaccine studies. Preferential infection of vaccine-induced CD4 T cells by HIV reduces the efficiency of vaccine-generated immunity. Our hypothesis is that a protective HIV vaccine should induce a type of vaccine-specific CD4 T cells that are "not readily susceptible" to HIV, and that different candidate HIV vaccines (e.g. different vectors) induce distinct phenotypes of vaccine- and/or vector-specific CD4 T cells that may impact their sensitivities to HIV. We will test peripheral blood mononuclear cell samples from three completed HIV vaccine trials: RV144 (ALVAC), RV158 (MVA) and IPCAVD 001(Ad26). Our hypotheses will be addressed in 2 Specific Aims: 1) To determine the role of IFIT1 in regulating the susceptibility of antigen-specific CD4 T cells to HIV and to further explore the mechanisms for inhibition of HIV by IFIT1; 2) To investigate the susceptibilities of different HIV vaccine-induced, antigen-specific CD4 T cells to HIV infection and the associated phenotypes in HIV vaccine trials. The proposed studies are exploratory, but expected to provide new insights to: 1) understand the mechanisms for the persistence of CMV-specific T cell immunity in AIDS patients; 2) identify a novel anti-HIV molecule with previously unidentified inhibitory mechanisms that could possibly lead to development of novel interventional strategies; 3) more thoroughly understand the quality of vaccine-generated CD4 T cell immunity and to provide proof of concept knowledge as to whether and how to induce functional, "HIV-resistant" CD4 T cells by an efficacious HIV vaccine.
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项目成果

期刊论文数量(0)
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Haitao Hu其他文献

Haitao Hu的其他文献

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{{ truncateString('Haitao Hu', 18)}}的其他基金

Modulation of BRD4 to epigenetically suppress HIV
调节 BRD4 以表观遗传抑制 HIV
  • 批准号:
    10624845
  • 财政年份:
    2021
  • 资助金额:
    $ 21.73万
  • 项目类别:
Modulation of BRD4 to epigenetically suppress HIV
调节 BRD4 以表观遗传抑制 HIV
  • 批准号:
    10326722
  • 财政年份:
    2021
  • 资助金额:
    $ 21.73万
  • 项目类别:
Modulation of BRD4 to epigenetically suppress HIV
调节 BRD4 以表观遗传抑制 HIV
  • 批准号:
    10434159
  • 财政年份:
    2021
  • 资助金额:
    $ 21.73万
  • 项目类别:
In vitro and in vivo analysis of susceptibility of Ad26 vector-induced CD4 T cells to HIV/SIV
Ad26载体诱导的CD4 T细胞对HIV/SIV敏感性的体外和体内分析
  • 批准号:
    10010193
  • 财政年份:
    2020
  • 资助金额:
    $ 21.73万
  • 项目类别:
In vitro and in vivo analysis of susceptibility of Ad26 vector-induced CD4 T cells to HIV/SIV
Ad26载体诱导的CD4 T细胞对HIV/SIV敏感性的体外和体内分析
  • 批准号:
    10115603
  • 财政年份:
    2020
  • 资助金额:
    $ 21.73万
  • 项目类别:
Susceptibility of antigen-specific CD4 T cells to HIV: implications for HIV vacci
抗原特异性 CD4 T 细胞对 HIV 的敏感性:对 HIV 疫苗的影响
  • 批准号:
    9070878
  • 财政年份:
    2014
  • 资助金额:
    $ 21.73万
  • 项目类别:

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