- 专利标题: Engineered outer domain (eOD) of HIV GP120, mutants and use thereof
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申请号: US15844753申请日: 2017-12-18
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公开(公告)号: US11248027B2公开(公告)日: 2022-02-15
- 发明人: William Schief , Sergey Menis , Daniel Kulp , Joseph Jardine
- 申请人: International AIDS Vaccine Initiative , The Scripps Research Institute
- 申请人地址: US NY New York; US CA La Jolla
- 专利权人: International AIDS Vaccine Initiative,The Scripps Research Institute
- 当前专利权人: International AIDS Vaccine Initiative,The Scripps Research Institute
- 当前专利权人地址: US NY New York; US CA La Jolla
- 代理机构: Duane Morris LLP
- 代理商 Thomas J. Kowalski; Deborah L. Lu
- 主分类号: C07K16/28
- IPC分类号: C07K16/28 ; A61K39/00 ; C07K16/00 ; A61K38/00 ; A61K39/395 ; C07K14/005 ; A01K67/027 ; A61K39/12 ; A61K39/21 ; A61K49/00 ; C12N7/00 ; C12N9/10
摘要:
The present invention relates to engineered outer domain (eOD) immunogens of HIV gp120 and mutants thereof and methods of making and using the same. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity. The mutant eODs bind to neutralizing antibody precursors. The mutant eODs can activate germline precursors on the pathway to eliciting a broadly neutralizing antibody (bnAb) response. The invention also relates to immunized knock-in mice expressing germline-reverted heavy chains. Induced antibodies showed characteristics of bnAbs and mutations that favored binding to near-native HIV-1 gp120 constructs. In contrast, native-like immunogens failed to activate precursors. The invention also relates to rational epitope design that can prime rare B cell precursors for affinity maturation to desired targets.
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