Development of a Pan-HIV Proteomic Chip

泛HIV蛋白质组芯片的开发

基本信息

  • 批准号:
    8659860
  • 负责人:
  • 金额:
    $ 22.5万
  • 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:
    2014-09-16 至 2016-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): HIV-1 causes the largest number of deaths from a single infectious agent in the world today. Despite considerable advances in treatment of HIV-1 infection and AIDS, which it causes, there is an urgent need for better methods of prevention and treatment of HIV-1 infection. The development of a safe and effective vaccine to prevent HIV-1 infection or the subsequent development of AIDS is therefore of the utmost importance. This effort, however, has been hampered by a lack of understanding of the correlates of protective immunity and a lack of the tools needed to measure effective anti-HIV-1 immune responses. We have developed a Multi-Clade HIV-1 Proteomic Chip (MC-HIV-1 chip) that can be used as a tool to rapidly screen antibody responses to HIV-1 elicited in vivo in response to infection or vaccination. The current version of the MC-HIV-1 chip which is available commercially from Antigen Discovery Incorporated (ADI) expresses over 100 HIV-1 proteins, protein fragments and epitopes from clades A1, A2, B, C and D which together comprise 74% of HIV-1 infections worldwide (Stephens 2012). Our preliminary studies show that the MC-HIV-1 chip can be used to identify the specificity of HIV-1 antibodies, track changes in the humoral immune response to HIV-1 during infection and may also be able to identify the clade of an HIV-1 infection. In this application we propose to improve the MC-HIV-1 chip by expanding it's coverage of HIV-1 subtypes, circulating recombinant forms (CRF), disulfide bound antigens, glycosylated antigens, epitopes and HIV-2 groups A and B thereby creating a Pan-HIV Proteomic Chip. We further propose to validate the MC-HIV chip and Pan HIV chip with a variety of sera and antibodies. We hypothesize that the improved Pan-HIV Chip will allow identification of the type, group and subtype of an HIV infection, will facilitate rapid characterization of humoral immune response to nearly all HIV infections and vaccination regimens, will identify reactivity with some broadly neutralizing epitopes and will differentiate natural from vaccine-induced humoral immunity. We have the following aims: 1 - We will expand the MC-HIV-1 chip to include HIV-1 subtype G, CRF01 AE and CRF01 AG as well as HIV-2 groups A and B, thereby creating a Pan-HIV chip. This will expand coverage to > 90% of HIV-1 infections and virtually all HIV-2 infections globally. 2 - We will improve the Pan-HIV chip by including disulfide bridges and glycosyl groups in the external proteins, gp120 and gp41, and in their fragments, including the variable loops of gp120. We will also include consensus sequences of key epitopes that differentiate clades as well as those that are the targets of braodly neutralizing (BN) antibodies. This will improve reactivity with BN and clade specific antibodies as well as antibodies that recognize conformational and glycosyl epitopes.3 - We will assay the ability of the current MC-HIV-1 chip as well as the improved Pan-HIV chip to react with patient sera from progressors, non-progressors, from early vs. late in infection, from patients infected with different types, groups and clades of HIV and following vaccination. We will also assay reactivity of all classes of broadly neutralizing monoclonal antibodies with the current and improved HIV chips. This aim will demonstrate the utility of the current MC-HIV-1 chip and improved Pan-HIV chip in vaccine research and in characterizing the humoral immune response to HIV infection. Future directions will include screening vaccinee sera and optimizing the Pan HIV chip for differentiating humoral immune responses to vaccinination from responses to natural infection.
描述(申请人提供):HIV-1是当今世界上单一传染病导致死亡人数最多的病毒。尽管在治疗HIV-1感染及其引起的艾滋病方面取得了相当大的进展,但仍然迫切需要更好的预防和治疗HIV-1感染的方法。因此,研制一种安全有效的疫苗来预防HIV-1感染或随后发展成艾滋病是至关重要的。然而,由于对保护性免疫的相关性缺乏了解,以及缺乏衡量有效的抗HIV-1免疫反应所需的工具,这一努力受到了阻碍。我们已经开发了一种多分支HIV-1蛋白质组芯片(MC-HIV-1芯片),可以用作快速筛选体内感染或疫苗接种引起的HIV-1抗体反应的工具。当前版本的MC-HIV-1芯片可从Antigen Discovery Incorporated(ADI)商购获得,其表达来自进化枝A1、A2、B、C和D的超过100种HIV-1蛋白、蛋白片段和表位,这些进化枝共占全球HIV-1感染的74%(Stephens 2012)。我们的初步研究表明,MC-HIV-1芯片可用于识别HIV-1抗体的特异性,跟踪感染期间对HIV-1的体液免疫反应的变化,也可能能够识别HIV-1感染的分支。在本申请中,我们提出通过扩大其对HIV-1亚型、循环重组形式(CRF)、二硫键结合抗原、糖基化抗原、表位和HIV-2组A和B的覆盖来改进MC-HIV-1芯片,从而创建泛HIV蛋白质组学芯片。我们进一步建议用各种血清和抗体验证MC-HIV芯片和Pan HIV芯片。我们假设,改进的泛HIV芯片将允许识别HIV感染的类型、组和亚型,将促进对几乎所有HIV感染和疫苗接种方案的体液免疫应答的快速表征,将识别与一些广泛中和表位的反应性,并将区分天然的和疫苗诱导的体液免疫。我们的目标如下:1 -我们将扩展MC-HIV-1芯片,包括HIV-1亚型G、CRF 01 AE和CRF 01 AG以及HIV-2 A和B组,从而创建泛HIV芯片。这将扩大覆盖面,覆盖全球90%以上的HIV-1感染和几乎所有HIV-2感染。2 -我们将通过在外部蛋白gp 120和gp 41及其片段(包括gp 120的可变环)中包括二硫键和糖基来改进泛HIV芯片。我们还将包括区分进化枝的关键表位的共有序列,以及那些是braodly中和(BN)抗体的靶点的序列。这将提高与BN和进化枝特异性抗体以及识别构象和糖基表位的抗体的反应性。3-我们将测定当前的MC-HIV-1芯片以及改进的Pan-HIV芯片与来自进展者、非进展者、来自感染早期与晚期、来自感染不同类型、组和进化枝的HIV的患者以及接种疫苗后的患者血清反应的能力。我们还将用现有的和改进的HIV芯片检测所有种类的广泛中和单克隆抗体的反应性。这一目标将证明目前的MC-HIV-1芯片和改进的泛HIV芯片在疫苗研究和表征对HIV感染的体液免疫反应中的实用性。未来的发展方向将包括筛选疫苗接种者血清和优化泛艾滋病毒芯片,以区分对疫苗接种的体液免疫反应和对自然感染的反应。

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)

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 }}

DAVID CAMERINI其他文献

DAVID CAMERINI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('DAVID CAMERINI', 18)}}的其他基金

Identification of Serodiagnostic Epitopes for SARS-CoV-2, endemic HCoV?s and influenza virus
SARS-CoV-2、地方性 HCoV 和流感病毒血清诊断表位的鉴定
  • 批准号:
    10259177
  • 财政年份:
    2021
  • 资助金额:
    $ 22.5万
  • 项目类别:
Discovery of Yellow Fever Virus-Specific Epitopes for Development of an Accurate Serodiagnostic Assay
发现黄热病病毒特异性表位以开发准确的血清诊断测定
  • 批准号:
    9467246
  • 财政年份:
    2018
  • 资助金额:
    $ 22.5万
  • 项目类别:
Specific Detection of Antibodies to Emerging and Established Arboviruses Including Zika Virus
针对新出现和已建立的虫媒病毒(包括寨卡病毒)的抗体的特异性检测
  • 批准号:
    9347926
  • 财政年份:
    2017
  • 资助金额:
    $ 22.5万
  • 项目类别:
Point of Care Detection of Oral Pathogens
口腔病原体的即时检测
  • 批准号:
    8973923
  • 财政年份:
    2015
  • 资助金额:
    $ 22.5万
  • 项目类别:
HIV Pathogenesis and Immunity in Viremic Non-Progressors
病毒血症非进展者的 HIV 发病机制和免疫
  • 批准号:
    8069963
  • 财政年份:
    2010
  • 资助金额:
    $ 22.5万
  • 项目类别:
HIV Pathogenesis and Immunity in Viremic Non-Progressors
病毒血症非进展者的 HIV 发病机制和免疫
  • 批准号:
    7931065
  • 财政年份:
    2010
  • 资助金额:
    $ 22.5万
  • 项目类别:
Defensin mediated inhibition of HIV-1 replication
防御素介导的 HIV-1 复制抑制
  • 批准号:
    6954219
  • 财政年份:
    2004
  • 资助金额:
    $ 22.5万
  • 项目类别:
Defensin mediated inhibition of HIV-1 replication
防御素介导的 HIV-1 复制抑制
  • 批准号:
    6845911
  • 财政年份:
    2004
  • 资助金额:
    $ 22.5万
  • 项目类别:
HIV-1 Clones with Attenuated Cytopathic Effects
细胞病变效应减弱的 HIV-1 克隆
  • 批准号:
    6744170
  • 财政年份:
    2003
  • 资助金额:
    $ 22.5万
  • 项目类别:
HIV-1 Clones with Attenuated Cytopathic Effects
细胞病变效应减弱的 HIV-1 克隆
  • 批准号:
    6655454
  • 财政年份:
    2003
  • 资助金额:
    $ 22.5万
  • 项目类别:

相似海外基金

University of Aberdeen and Vertebrate Antibodies Limited KTP 23_24 R1
阿伯丁大学和脊椎动物抗体有限公司 KTP 23_24 R1
  • 批准号:
    10073243
  • 财政年份:
    2024
  • 资助金额:
    $ 22.5万
  • 项目类别:
    Knowledge Transfer Partnership
Role of Natural Antibodies and B1 cells in Fibroproliferative Lung Disease
天然抗体和 B1 细胞在纤维增生性肺病中的作用
  • 批准号:
    10752129
  • 财政年份:
    2024
  • 资助金额:
    $ 22.5万
  • 项目类别:
CAREER: Next-generation protease inhibitor discovery with chemically diversified antibodies
职业:利用化学多样化的抗体发现下一代蛋白酶抑制剂
  • 批准号:
    2339201
  • 财政年份:
    2024
  • 资助金额:
    $ 22.5万
  • 项目类别:
    Continuing Grant
Isolation and characterisation of monoclonal antibodies for the treatment or prevention of antibiotic resistant Acinetobacter baumannii infections
用于治疗或预防抗生素耐药鲍曼不动杆菌感染的单克隆抗体的分离和表征
  • 批准号:
    MR/Y008693/1
  • 财政年份:
    2024
  • 资助金额:
    $ 22.5万
  • 项目类别:
    Research Grant
Developing first-in-class aggregation-specific antibodies for a severe genetic neurological disease
开发针对严重遗传神经系统疾病的一流聚集特异性抗体
  • 批准号:
    10076445
  • 财政年份:
    2023
  • 资助金额:
    $ 22.5万
  • 项目类别:
    Grant for R&D
Discovery of novel nodal antibodies in the central nervous system demyelinating diseases and elucidation of the mechanisms through an optic nerve demyelination model
发现中枢神经系统脱髓鞘疾病中的新型节点抗体并通过视神经脱髓鞘模型阐明其机制
  • 批准号:
    23K14783
  • 财政年份:
    2023
  • 资助金额:
    $ 22.5万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Elucidation of the mechanisms controlling the physicochemical properties and functions of supercharged antibodies and development of their applications
阐明控制超电荷抗体的理化性质和功能的机制及其应用开发
  • 批准号:
    23KJ0394
  • 财政年份:
    2023
  • 资助金额:
    $ 22.5万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Role of antibodies in hepatitis E virus infection
抗体在戊型肝炎病毒感染中的作用
  • 批准号:
    10639161
  • 财政年份:
    2023
  • 资助金额:
    $ 22.5万
  • 项目类别:
Defining the protective or pathologic role of antibodies in Post-Ebola Syndrome
定义抗体在埃博拉后综合症中的保护或病理作用
  • 批准号:
    10752441
  • 财政年份:
    2023
  • 资助金额:
    $ 22.5万
  • 项目类别:
Human CMV monoclonal antibodies as therapeutics to inhibit virus infection and dissemination
人 CMV 单克隆抗体作为抑制病毒感染和传播的治疗药物
  • 批准号:
    10867639
  • 财政年份:
    2023
  • 资助金额:
    $ 22.5万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了