Antigen-specific ‘kick and kill’ of the latent HIV reservoir using dendritic cells

使用树突状细胞对潜伏 HIV 病毒库进行抗原特异性“踢杀”

基本信息

项目摘要

ABSTRACT The persistence of the latent viral reservoir remains a hurdle for the cure of chronic HIV infection. Finding an effective and non-toxic means to purge and expose the viral reservoir has been elusive and is considered a major barrier to the cure. Because of their pivotal role in the initiation and regulation of adaptive T cell immunity, dendritic cells (DC) have been a therapeutic target for both cancer and HIV. Our most recent findings show that with optimal programming, DC have the provocative potential to both drive expansion of HIV-specific cytotoxic T cell lymphocytes (CTL), and to effectively induce HIV latency reversal (LR) to expose the infected cells for CTL targeting and elimination. We have determined that our specialized IL-12p70-producing type-1 polarized monocyte derived DC therapeutic platform (MDC1) can facilitate HIV LR when loaded with either CMV or HIV immunogenic peptides, suggesting that a considerable component of the HIV cellular reservoir is contained among CMV- and HIV specific CD4+ T cells. Here we propose the optimization of MDC1-based immunotherapy strategy that utilizes MHC class II associated CMV epitopes along with highly conserved MHC class I restricted HIV peptides as combined antigenic components designed to facilitate both the exposure of CD4+ T cells harboring latent HIV (the ‘kick’) and their elimination by HIV specific CTL (the ‘kill’). In our proposed studies we will dig deeper into the mechanisms involved, and we will translate our in vitro findings to test this approach in vivo using a humanized mouse model of HIV infection and MDC1 immunotherapy.
摘要 潜伏病毒库的持续存在仍然是治愈慢性HIV感染的障碍。找到一个 清除和暴露病毒储库的有效且无毒的方法一直是难以捉摸的, 治愈的主要障碍由于它们在启动和调节适应性T细胞免疫中的关键作用, 树突状细胞(DC)已经成为癌症和HIV的治疗靶点。我们最新的发现表明, 通过最佳编程,DC具有刺激潜力,既可以驱动HIV特异性细胞毒性药物的扩张, T细胞淋巴细胞(CTL),并有效地诱导HIV潜伏期逆转(LR),使受感染的细胞暴露于CTL 锁定目标和消灭我们已经确定,我们的专门IL-12 p70生产型1极化 单核细胞衍生的DC治疗平台(MDC 1)在负载CMV或HIV时可促进HIV LR 免疫原性肽,这表明HIV细胞库的相当大的组成部分被包含 CMV-和HIV特异性CD 4 + T细胞之间。在这里,我们提出了基于MDC 1的免疫疗法的优化 利用MHC II类相关CMV表位沿着高度保守的MHC I类限制性 HIV肽作为组合抗原成分,设计用于促进CD 4 + T细胞暴露 携带潜伏的HIV(“踢”)和它们被HIV特异性CTL消除(“踢”)。在我们提出的研究中, 我们将更深入地研究所涉及的机制,我们将把我们的体外研究结果转化为测试这种方法, 使用HIV感染的人源化小鼠模型和MDC 1免疫疗法在体内进行。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Moses Turkle Bility其他文献

Moving beyond the mousetrap: current and emerging humanized mouse and rat models for investigating prevention and cure strategies against HIV infection and associated pathologies
  • DOI:
    10.1186/s12977-020-00515-3
  • 发表时间:
    2020-04-10
  • 期刊:
  • 影响因子:
    3.900
  • 作者:
    Yash Agarwal;Cole Beatty;Shivkumar Biradar;Isabella Castronova;Sara Ho;Kevin Melody;Moses Turkle Bility
  • 通讯作者:
    Moses Turkle Bility

Moses Turkle Bility的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Moses Turkle Bility', 18)}}的其他基金

Antigen-specific ‘kick and kill’ of the latent HIV reservoir using dendritic cells
使用树突状细胞对潜伏 HIV 病毒库进行抗原特异性“踢杀”
  • 批准号:
    10401605
  • 财政年份:
    2021
  • 资助金额:
    $ 63.46万
  • 项目类别:
Role of macrophage activation in HBV/HIV co-infection-induced liver disease
巨噬细胞激活在 HBV/HIV 合并感染引起的肝病中的作用
  • 批准号:
    9453233
  • 财政年份:
    2017
  • 资助金额:
    $ 63.46万
  • 项目类别:

相似国自然基金

Neo-antigens暴露对肾移植术后体液性排斥反应的影响及其机制研究
  • 批准号:
    2022J011295
  • 批准年份:
    2022
  • 资助金额:
    10.0 万元
  • 项目类别:
    省市级项目
结核分枝杆菌持续感染期抗原(latency antigens)的重组BCG疫苗研究
  • 批准号:
    30801055
  • 批准年份:
    2008
  • 资助金额:
    19.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

Bovine herpesvirus 4 as a vaccine platform for African swine fever virus antigens in pigs
牛疱疹病毒 4 作为猪非洲猪瘟病毒抗原的疫苗平台
  • 批准号:
    BB/Y006224/1
  • 财政年份:
    2024
  • 资助金额:
    $ 63.46万
  • 项目类别:
    Research Grant
Uncovering tumor specific antigens and vulnerabilities in ETP-acute lymphoblastic leukemia
揭示 ETP-急性淋巴细胞白血病的肿瘤特异性抗原和脆弱性
  • 批准号:
    480030
  • 财政年份:
    2023
  • 资助金额:
    $ 63.46万
  • 项目类别:
    Operating Grants
A novel vaccine approach combining mosquito salivary antigens and viral antigens to protect against Zika, chikungunya and other arboviral infections.
一种结合蚊子唾液抗原和病毒抗原的新型疫苗方法,可预防寨卡病毒、基孔肯雅热和其他虫媒病毒感染。
  • 批准号:
    10083718
  • 财政年份:
    2023
  • 资助金额:
    $ 63.46万
  • 项目类别:
    Small Business Research Initiative
Regulation of B cell responses to vaccines by long-term retention of antigens in germinal centres
通过在生发中心长期保留抗原来调节 B 细胞对疫苗的反应
  • 批准号:
    MR/X009254/1
  • 财政年份:
    2023
  • 资助金额:
    $ 63.46万
  • 项目类别:
    Research Grant
Adaptive Discrimination of Risk of Antigens in Immune Memory Dynamics
免疫记忆动态中抗原风险的适应性辨别
  • 批准号:
    22KJ1758
  • 财政年份:
    2023
  • 资助金额:
    $ 63.46万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
22-ICRAD Call 2 - Improving the diagnosis of tuberculosis in domestic ruminants through the use of new antigens and test platforms
22-ICRAD 呼吁 2 - 通过使用新抗原和测试平台改善家养反刍动物结核病的诊断
  • 批准号:
    BB/Y000927/1
  • 财政年份:
    2023
  • 资助金额:
    $ 63.46万
  • 项目类别:
    Research Grant
Protective immunity elicited by distinct polysaccharide antigens of classical and hypervirulent Klebsiella
经典和高毒力克雷伯氏菌的不同多糖抗原引发的保护性免疫
  • 批准号:
    10795212
  • 财政年份:
    2023
  • 资助金额:
    $ 63.46万
  • 项目类别:
Integrative proteome analysis to harness humoral immune response against tumor antigens
综合蛋白质组分析利用针对肿瘤抗原的体液免疫反应
  • 批准号:
    23K18249
  • 财政年份:
    2023
  • 资助金额:
    $ 63.46万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
Functionally distinct human CD4 T cell responses to novel evolutionarily selected M. tuberculosis antigens
功能独特的人类 CD4 T 细胞对新型进化选择的结核分枝杆菌抗原的反应
  • 批准号:
    10735075
  • 财政年份:
    2023
  • 资助金额:
    $ 63.46万
  • 项目类别:
Targeting T3SA proteins as protective antigens against Yersinia
将 T3SA 蛋白作为针对耶尔森氏菌的保护性抗原
  • 批准号:
    10645989
  • 财政年份:
    2023
  • 资助金额:
    $ 63.46万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了