Core-002
Core-002
批准号:
10794904
负责人:
Richard Thomas Wyatt
金额:
$113.05万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-02-04 至 2026-01-31
中文摘要
点击翻译按钮获取中文摘要
英文摘要
Abstract
Structure-based vaccine design holds great promise for combatting viral pathogens that create substantial
burdens on global health. For HIV, the soluble ectodomain of the envelope glycoprotein (Env), which is the
primary target for neutralizing antibody responses, is the focal point for vaccine design. Several different
platforms of stable, soluble Env trimers locked in a prefusion, antigenically optimal, conformation are now
available and provide the basis for further design efforts. The investigators of this grant developed the native
flexibly-linked (NFL) platform, which does not require furin cleavage. The Ward and Wilson labs (Co-PIs of the
Structure Core) have shown that NFL trimers adopt native-like structures and the Wyatt lab (Project 1) that they
induce neutralizing antibody responses in rabbits and guinea pigs. In fact, a small subset of monoclonal
antibodies that have been isolated from these animals show some neutralization breadth, a key next step in
trimer-based vaccine design. We have already mapped these antibodies by electron microscopy and showed
that one antibody targets an epitope that overlaps with the CD4bs and another targets an epitope near the base
of the trimer, similar to some known human broadly neutralizing antibodies. These desirable immune responses
are relatively infrequent, but show the promise of these trimer-based immunogens. Based on new structural
information and the desire to improve the antigenicity and immunogenicity, further NFL trimers are continually
being redesigned. For example, the NFL platform has been elaborated to include the MPER as well as a glycan-depleted version that increases accessibility of the CD4bs, and has been successfully been incorporated into
liposomes for multivalent presentation. Each new design was enabled by the available structural information.
Hence, this core will continue to provide the necessary structural information to drive Env trimer vaccine
innovation in an iterative manner, at the front-end aiding in the design of new immunogens (with Project 1), in
the middle by informing boosting strategies using our EM serum profiling analysis (with Project 2), and at the
back-end by evaluating the antibody responses to such immunogens at low and high resolution (with Project 2).
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Eliciting neutralizing antibodies and B cell responses using novel HIV Env immunogens in non-human primates
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批准号:10339439
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项目类别:
-
资助金额:$342.0万
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财政年份:2021
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负责人:Richard Thomas Wyatt
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依托单位:
Project 1
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批准号:10339443
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项目类别:
-
资助金额:$115.59万
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财政年份:2021
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负责人:Richard Thomas Wyatt
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依托单位:
Admin Core
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批准号:10339440
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项目类别:
-
资助金额:$21.4万
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财政年份:2021
-
负责人:Richard Thomas Wyatt
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依托单位:
Core-001
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批准号:10782243
-
项目类别:
-
资助金额:$139.64万
-
财政年份:2021
-
负责人:Richard Thomas Wyatt
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依托单位:
Project-002
-
批准号:10794919
-
项目类别:
-
资助金额:$50.33万
-
财政年份:2021
-
负责人:Richard Thomas Wyatt
-
依托单位:
Eliciting neutralizing antibodies and B cell responses using novel HIV Env immunogens in non-human primates
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批准号:10549838
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项目类别:
-
资助金额:$340.27万
-
财政年份:2021
-
负责人:Richard Thomas Wyatt
-
依托单位:
Admin-Core-001
-
批准号:10794918
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项目类别:
-
资助金额:$37.25万
-
财政年份:2021
-
负责人:Richard Thomas Wyatt
-
依托单位:
N-glycan baiting to target the highly effective HIV Env shield
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批准号:10388295
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项目类别:
-
资助金额:$96.18万
-
财政年份:2019
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负责人:Richard Thomas Wyatt
-
依托单位:
N-glycan baiting to target the highly effective HIV Env shield
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批准号:9754560
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项目类别:
-
资助金额:$67.15万
-
财政年份:2019
-
负责人:Richard Thomas Wyatt
-
依托单位:
N-glycan baiting to target the highly effective HIV Env shield
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批准号:10333202
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项目类别:
-
资助金额:$96.18万
-
财政年份:2019
-
负责人:Richard Thomas Wyatt
-
依托单位:
N-glycan baiting to target the highly effective HIV Env shield
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批准号:9918868
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项目类别:
-
资助金额:$67.15万
-
财政年份:2019
-
负责人:Richard Thomas Wyatt
-
依托单位:
High Resolution Analysis of Env-directed B Cells to Accelerate Vaccine Design
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批准号:8680621
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项目类别:
-
资助金额:$265.98万
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财政年份:2014
-
负责人:Richard Thomas Wyatt
-
依托单位:
Structure and Immunogenicity of HIV-1 gp41 Membrane Prox
-
批准号:7299877
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项目类别:
-
资助金额:$0.0万
-
财政年份:--
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负责人:Richard Thomas Wyatt
-
依托单位:
Immmunogenicity and Structure of trimeric HIV-1 gp120 gl
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批准号:7184287
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项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:Richard Thomas Wyatt
-
依托单位:
HIV-1 Solid Phase Proteoliposome
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批准号:7184256
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项目类别:
-
资助金额:$0.0万
-
财政年份:--
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负责人:Richard Thomas Wyatt
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依托单位:
Biophysics /Structure /Immunogenicity of HIV-1Glycoprote
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批准号:7189318
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项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:Richard Thomas Wyatt
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依托单位:
Production And Characterization Of HIV-1 Solid Phase Proteoliposomes
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批准号:7732748
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项目类别:
-
资助金额:$41.47万
-
财政年份:--
-
负责人:Richard Thomas Wyatt
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依托单位:
Determination of the Neutralization Specificity in Broadly Neutralizing HIV Sera
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批准号:7592436
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项目类别:
-
资助金额:$19.16万
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财政年份:--
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负责人:Richard Thomas Wyatt
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依托单位:
Administrative Core
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批准号:8829138
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项目类别:
-
资助金额:$10.27万
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财政年份:--
-
负责人:Richard Thomas Wyatt
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依托单位:
Administrative Core
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批准号:8680626
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项目类别:
-
资助金额:$11.26万
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财政年份:--
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负责人:Richard Thomas Wyatt
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依托单位:
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