RAPID FLUOROMETRIC ASSAY OF HIV-INDUCED CELL FUSION
RAPID FLUOROMETRIC ASSAY OF HIV-INDUCED CELL FUSION
批准号:
2067703
负责人:
PAUL J MADDON
金额:
$19.64万
依托单位国家:
美国
项目类别:
财政年份:
1992
资助国家:
美国
项目状态:
已结题
起止时间:
1992-04-01 至 1995-12-31
关键词:
CD4 molecule HIV envelope protein gp120 HIV envelope protein gp41 HIV infections antiviral antibody biomedical automation cell fusion human immunodeficiency virus 1 human tissue immunofluorescence technique membrane fusion method development microorganism immunology monoclonal antibody neutralizing antibody virus infection mechanism virus receptors
中文摘要
表达HIV-1包膜糖蛋白gpl20/gp4l的细胞可以融合
英文摘要
Cells that express gpl20/gp4l, the HIV-1 envelope glycoprotein, can fuse
with cells expressing CD4, the HIV-1 receptor, to form multinucleated
giant cells or syncytia. Such cell-to-cell fusion appears to be a
mechanism for virus transmission as well as a primary cause of cell death
in HIV-1 infection. In addition, cell fusion can serve as a model system
of viral entry to study HIV-1 envelope-mediated membrane fusion, the
initial phase in the predicative cycle of the virus. During Phase I
period, the investigators successfully developed an HIV-1 envelope-
mediated fusion assay using cells that stably express gp120/gp4l from a
laboratory-adapted strain and human cells expressing CD4. They then
demonstrated that fusion between these cells can be measured using a novel
fluorescence-based assay. Their system has several major advantages over
already existing assays. It is virus-free, reproducible, sensitive, and
rapid. It is also suitable for quantitative and kinetic analyses,
providing an accurate and objective measurement of membrane fusion. During
the Phase II period, they will automate and optimize the fluorescence-
based fusion assay in order to rapidly analyze multiple samples. In
addition, they will develop an automated fluorescence fusion assay using
a cell line stably expressing gp2l0/gp4l from a primary isolate of HIV-1.
These assays will permit a detailed analysis of membrane fusion mediated
by envelope glycoproteins from viruses that exhibit markedly different
tropisms for human cells. They will then use these assays to identify
novel, functionally relevant human monoclonal antibodies (huMAbs) that
interact with authentic, oligomeric gpl20/gp4l. To date, huMAbs have been
selected by their ability to bind peptides or recombinant gp120 in an
ELISA format that severely restricts the identification of functionally
relevant huMAbs.huMAbs will be generated from HIV-l infected individuals,
including long-term survivors, and tested as single agents or in
combination with CD4-based molecules. In particular, huMAbs from long-
term survivors, which are not currently available, may possess unusual
characteristics and provide a unique insight into a protective immune
response. Finally, they will extensively characterize the structural and
functional properties of the huMAbs in order to select those most suitable
for development as immunotherapeutics in Phase III.
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批准号:6746752
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项目类别:
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资助金额:$30.36万
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财政年份:2004
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负责人:PAUL J MADDON
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依托单位:
Development of Small-Molecule HIV Entry Inhibitors
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批准号:6698946
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项目类别:
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资助金额:$89.94万
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财政年份:2001
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负责人:PAUL J MADDON
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依托单位:
HIV Vaccine Design and Development Team
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批准号:6374728
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项目类别:
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资助金额:$209.05万
-
财政年份:2000
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负责人:PAUL J MADDON
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依托单位:
HIV Vaccine Design and Development Team
-
批准号:6348770
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项目类别:
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资助金额:$197.43万
-
财政年份:2000
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负责人:PAUL J MADDON
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依托单位:
CLINICAL TRIALS OF CD4 IGG2 AND HUMAB COMBINATIONS
-
批准号:2887738
-
项目类别:
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资助金额:$54.6万
-
财政年份:1998
-
负责人:PAUL J MADDON
-
依托单位:
CLINICAL TRIALS OF CD4 IGG2 AND HUMAB COMBINATIONS
-
批准号:2643926
-
项目类别:
-
资助金额:$54.6万
-
财政年份:1998
-
负责人:PAUL J MADDON
-
依托单位:
CLINICAL TRIALS OF CD4 IGG2 AND HUMAB COMBINATIONS
-
批准号:6373836
-
项目类别:
-
资助金额:$54.6万
-
财政年份:1998
-
负责人:PAUL J MADDON
-
依托单位:
CLINICAL TRIALS OF CD4 IGG2 AND HUMAB COMBINATIONS
-
批准号:6510836
-
项目类别:
-
资助金额:$54.6万
-
财政年份:1998
-
负责人:PAUL J MADDON
-
依托单位:
CLINICAL TRIALS OF CD4 IGG2 AND HUMAB COMBINATIONS
-
批准号:6170605
-
项目类别:
-
资助金额:$54.6万
-
财政年份:1998
-
负责人:PAUL J MADDON
-
依托单位:
DEVELOPMENT OF ANTICO RECEPTOR MABS FOR HIV THERAPY
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批准号:2793411
-
项目类别:
-
资助金额:$52.06万
-
财政年份:1996
-
负责人:PAUL J MADDON
-
依托单位:
POST EXPOSURE PROPHYLAXIS AGAINST HIV 1 BY CD4 IGG2
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批准号:2545220
-
项目类别:
-
资助金额:$37.52万
-
财政年份:1996
-
负责人:PAUL J MADDON
-
依托单位:
DEVELOPMENT OF ANTICO RECEPTOR MABS FOR HIV THERAPY
-
批准号:6170001
-
项目类别:
-
资助金额:$59.45万
-
财政年份:1996
-
负责人:PAUL J MADDON
-
依托单位:
DEVELOPMENT OF ANTICO RECEPTOR MABS FOR HIV THERAPY
-
批准号:6373597
-
项目类别:
-
资助金额:$81.34万
-
财政年份:1996
-
负责人:PAUL J MADDON
-
依托单位:
POST EXPOSURE PROPHYLAXIS AGAINST HIV 1 BY CD4 IGG2
-
批准号:2004162
-
项目类别:
-
资助金额:$37.48万
-
财政年份:1996
-
负责人:PAUL J MADDON
-
依托单位:
POSTEXPOSURE PROPHYLAXIS AGAINST HIV 1 BY CD4 IGG2
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批准号:2073306
-
项目类别:
-
资助金额:$9.98万
-
财政年份:1995
-
负责人:PAUL J MADDON
-
依托单位:
RAPID FLUOROMETRIC ASSAY OF HIV-INDUCED CELL FUSION
-
批准号:3489609
-
项目类别:
-
资助金额:$5.0万
-
财政年份:1992
-
负责人:PAUL J MADDON
-
依托单位:
RAPID FLUOROMETRIC ASSAY OF HIV-INDUCED CELL FUSION
-
批准号:2067704
-
项目类别:
-
资助金额:$26.75万
-
财政年份:1992
-
负责人:PAUL J MADDON
-
依托单位:
HIGH-LEVEL EXPRESSION OF HIV GP120 IN MAMMALIAN CELLS
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批准号:2066683
-
项目类别:
-
资助金额:$21.21万
-
财政年份:1991
-
负责人:PAUL J MADDON
-
依托单位:
HIGH-LEVEL EXPRESSION OF HIV GP120 IN MAMMALIAN CELLS
-
批准号:3489513
-
项目类别:
-
资助金额:$4.97万
-
财政年份:1991
-
负责人:PAUL J MADDON
-
依托单位:
HIGH-LEVEL EXPRESSION OF HIV GP120 IN MAMMALIAN CELLS
-
批准号:2066684
-
项目类别:
-
资助金额:$28.78万
-
财政年份:1991
-
负责人:PAUL J MADDON
-
依托单位: