Discovery and Targeting of HIV-1 Associated Antigens

HIV-1 相关抗原的发现和靶向

基本信息

项目摘要

DESCRIPTION (provided by applicant): While searching for HIV-1 peptides that distinguish the HLA class I of infected cells, we found that a number of host-derived peptides are unique to HIV-1 infected cells. In aim 1 we propose to discover HLA class I presented host peptides that distinguish HIV-1 infected cells. Using a unique immunoproteomics approach we will catalog targets that HIV-1 cannot antigenically vary. Having discovered host peptide/HLA complexes that distinguish infected cells, we will next pursue the immune targeting of these complexes. A concern in targeting host peptides presented by the HLA of HIV-1 infected cells is autoimmunity; T cell responses (including memory responses) might target host peptides on uninfected cells. In aim 2 we will derive monoclonal antibodies that mimic the T cell receptor's specificity for peptide/HLA complexes (TCR mimics or TCRm antibodies). The goal is to passively administer these TCRm antibodies for the targeting of HIV-1 infected cells. In aim 3 the anti-viral activity of these TCRm antibodies will be tested. In summary, we will apply a proven immunoproteomics approach to identify unrealized HLA presented host peptides that distinguish HIV-1 infected cells. Furthermore, we will target HIV-1 specific host peptides with a new class of antibodies: TCRm. These novel antibodies will be systematically tested for antiviral effects in cell lines, primary human PBMC and against primary HIV-1 isolates. The ultimate goal is to test whether passive administration of TCRm antibodies will impact HIV-1 replication while bypassing the autoimmune consequences of targeting host epitopes.) Public Health Statement: HIV has been able to elude or defeat immune responses that directly target the virus. We hypothesize that the indirect targeting of HIV infected cells can block transmission of the virus. The goal of this study is to first identify changes unique to the infected cell and to then indirectly attack HIV by targeting infected cells with a new class of antibodies. We intend to target factors that the virus requires rather than the virus itself.
描述(由申请人提供):

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Abacavir induces loading of novel self-peptides into HLA-B*57: 01: an autoimmune model for HLA-associated drug hypersensitivity.
  • DOI:
    10.1097/qad.0b013e328355fe8f
  • 发表时间:
    2012-07-17
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Norcross MA;Luo S;Lu L;Boyne MT;Gomarteli M;Rennels AD;Woodcock J;Margulies DH;McMurtrey C;Vernon S;Hildebrand WH;Buchli R
  • 通讯作者:
    Buchli R
Direct interrogation of viral peptides presented by the class I HLA of HIV-infected T cells.
直接询问 HIV 感染 T 细胞的 I 类 HLA 呈递的病毒肽。
  • DOI:
    10.1128/jvi.01914-14
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    5.4
  • 作者:
    Yaciuk,JaneC;Skaley,Matthew;Bardet,Wilfried;Schafer,Fredda;Mojsilovic,Danijela;Cate,Steven;Stewart,ChristopherJ;McMurtrey,Curtis;Jackson,KennethW;Buchli,Rico;Olvera,Alex;Cedeño,Samandhy;Plana,Montserrat;Mothe,Beatriz;Brander
  • 通讯作者:
    Brander
Expanding the targets available to therapeutic antibodies via novel disease-specific markers.
  • DOI:
    10.3109/08830185.2011.608136
  • 发表时间:
    2011-10
  • 期刊:
  • 影响因子:
    5
  • 作者:
    Weidanz JA;Hildebrand WH
  • 通讯作者:
    Hildebrand WH
TCR-like biomolecules target peptide/MHC Class I complexes on the surface of infected and cancerous cells.
  • DOI:
    10.3109/08830185.2011.604880
  • 发表时间:
    2011-10
  • 期刊:
  • 影响因子:
    5
  • 作者:
    Weidanz JA;Hawkins O;Verma B;Hildebrand WH
  • 通讯作者:
    Hildebrand WH
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William Hildebrand其他文献

William Hildebrand的其他文献

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{{ truncateString('William Hildebrand', 18)}}的其他基金

rPIV5- and AVLP-vectored vaccine development with public tumor-specific neoantigens
使用公共肿瘤特异性新抗原开发 rPIV5 和 AVLP 载体疫苗
  • 批准号:
    10831315
  • 财政年份:
    2021
  • 资助金额:
    $ 47.92万
  • 项目类别:
Canine MHC-I genotyping and tumor specific neoantigen determination
犬 MHC-I 基因分型和肿瘤特异性新抗原测定
  • 批准号:
    10404109
  • 财政年份:
    2021
  • 资助金额:
    $ 47.92万
  • 项目类别:
Canine MHC-I genotyping and tumor specific neoantigen determination
犬 MHC-I 基因分型和肿瘤特异性新抗原测定
  • 批准号:
    10630913
  • 财政年份:
    2021
  • 资助金额:
    $ 47.92万
  • 项目类别:
Canine MHC-I genotyping and tumor specific neoantigen determination
犬 MHC-I 基因分型和肿瘤特异性新抗原测定
  • 批准号:
    10220542
  • 财政年份:
    2021
  • 资助金额:
    $ 47.92万
  • 项目类别:
Human natural killer cell recognition of cytomegalovirus
人类自然杀伤细胞对巨细胞病毒的识别
  • 批准号:
    8617610
  • 财政年份:
    2014
  • 资助金额:
    $ 47.92万
  • 项目类别:
Direct Discovery of HLA-associated Influenza Epitopes
HLA 相关流感表位的直接发现
  • 批准号:
    8481492
  • 财政年份:
    2012
  • 资助金额:
    $ 47.92万
  • 项目类别:
Direct Discovery of HLA-associated Influenza Epitopes
HLA 相关流感表位的直接发现
  • 批准号:
    8434472
  • 财政年份:
    2012
  • 资助金额:
    $ 47.92万
  • 项目类别:
Discovery and Targeting of HIV-1 Associated Antigens
HIV-1 相关抗原的发现和靶向
  • 批准号:
    8106378
  • 财政年份:
    2010
  • 资助金额:
    $ 47.92万
  • 项目类别:
Discovery and Targeting of HIV-1 Associated Antigens
HIV-1 相关抗原的发现和靶向
  • 批准号:
    7984351
  • 财政年份:
    2010
  • 资助金额:
    $ 47.92万
  • 项目类别:
Discovery and Targeting of HIV-1 Associated Antigens
HIV-1 相关抗原的发现和靶向
  • 批准号:
    8288353
  • 财政年份:
    2010
  • 资助金额:
    $ 47.92万
  • 项目类别:

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    2024
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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
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开发针对严重遗传神经系统疾病的一流聚集特异性抗体
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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
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