序号 专利名 申请号 申请日 公开(公告)号 公开(公告)日 发明人
1 ENGINEERED OUTER DOMAIN (EOD) OF HIV GP120, MUTANTS AND USE THEREOF US15844753 2017-12-18 US20180194809A1 2018-07-12 William Schief; Sergey Menis; Daniel Kulp; Joseph Jardine
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.
2 CHIMERAS OF BRUCELLA LUMAZINE SYNTHASE AND BETA SUBUNIT OF AB5 TOXINS US14894484 2014-05-26 US20160115459A1 2016-04-28 Fernando Alberto GOLDBAUM; Vanesa ZYLBERMAN; Patricio Oliver CRAIG; Giselle GHERSI; Marina Sandra PALERMO; Maria Pilar MEJIAS; Leticia Veronica BENTANCOR
Chimeric polypeptides useful as immunogens for inducing protective immune responses and neutralizing antibodies against Shiga toxin (Stx) in mammals. More specifically, chimeric polypeptides having a monomer of the homopentameric B subunit of the Shiga 2 toxin fused to the N-terminus of a monomer of Brucella lumazine synthase, and to oligomeric protein complexes formed from said chimeric polypeptides. Polynucleotides and vectors encoding said chimeric polypeptides, transgenic cells having said polynucleotides and vectors, pharmaceutical compositions, such as a vaccine, having said chimeric polypeptides and chimeric polynucleotides, antibodies which bind to the chimeric polypeptides, a method for obtaining antibodies which bind specifically to the subunit B of the Shiga 2 toxin and methods of lowering the bacterial load of enterohemorrhagic Escherichia coli in mammals, which can be used for prevention of inter cilia, hemolytic-ureic syndrome (HUS), are also provided.
3 BrucellaルマジンシンターゼとAB5毒素のBサブユニットとのキメラ JP2016516279 2014-05-26 JP2016522209A 2016-07-28 シュパッツ,マーティン,ディエゴ,ライナス; ゴールドバウム,フェルナンド,アルベルト; ジルバーマン,ヴァネサ; クレイグ,パトリシオ,オリバー; ゲルシ,ジゼル; パレルモ,マリナ,サンドラ; メヒアス,マリア,ピラー; ベンタンコール,レチシア,ヴェロニカ
本発明は、哺乳動物の志賀毒素(Stx)に対する防御免疫応答および中和抗体を誘導するための免疫原として有用なキメラポリペプチドに関する。より具体的には、本発明は、BrucellaルマジンシンターゼのモノマーのN末端に融合された志賀2毒素のホモ五量体Bサブユニットのモノマーを含むキメラポリペプチド、およびそのキメラポリペプチドから形成されるオリゴマー蛋白質複合体に関する。本発明は、そのキメラポリペプチドをコードするポリヌクレオチドおよびベクター、そのポリヌクレオチドおよびベクターを含むトランスジェニック細胞、ならびにそのキメラポリペプチドおよびキメラポリヌクレオチドを含むワクチンなどの医薬組成物にさらに関する。本発明のキメラポリペプチドに結合する抗体、志賀2毒素のサブユニットBに特異的に結合する抗体を得るための方法、および哺乳動物内の腸管出血性大腸菌の細菌量を低下させる方法もまた本発明の範囲内であり、とりわけ溶血性尿毒症症候群(hemolytic-ureic syndrome)(HUS)の予防のために用いられ得る。
4 CHIMERAS OF BRUCELLA LUMAZINE SYNTHASE AND BETA SUBUNIT OF AB5 TOXINS EP14736442.6 2014-05-26 EP3003348A1 2016-04-13 SPATZ, Martín, Diego, Linus; GOLDBAUM, Fernando, Alberto; ZYLBERMAN, Vanesa; CRAIG, Patricio, Oliver; GHERSI, Giselle; PALERMO, Marina, Sandra; MEJIAS, Maria, Pilar; BENTANCOR, Leticia, Veronica
Chimeric polypeptides useful as immunogens for inducing protective immune responses and neutralizing antibodies against Shiga toxin (Stx) in mammals. More specifically, chimeric polypeptides having a monomer of the homopentameric B subunit of the Shiga 2 toxin fused to the N-terminus of a monomer of Brucella lumazine synthase, and to oligomeric protein complexes formed from said chimeric polypeptides. Polynucleotides and vectors encoding said chimeric polypeptides, transgenic cells having said polynucleotides and vectors, pharmaceutical compositions, such as a vaccine, having said chimeric polypeptides and chimeric polynucleotides, antibodies which bind to the chimeric polypeptides, a method for obtaining antibodies which bind specifically to the subunit B of the Shiga 2 toxin and methods of lowering the bacterial load of enterohemorrhagic Escherichia coli in mammals, which can be used for prevention of inter cilia, hemolytic-ureic syndrome (HUS), are also provided.
5 ENGINEERED OUTER DOMAIN (EOD) OF HIV GP120, MUTANTS AND USE THEREOF EP16812553.2 2016-06-17 EP3334446A2 2018-06-20 SCHIEF, William; MENIS, Sergey; KULP, Daniel; JARDINE, Joseph
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.
6 브루셀라 균 주요 공통 항원을 발현하는 비병원성 약독화 살모넬라 균주를 포함하는 브루셀라증 예방 또는 치료용 백신 조성물 KR1020160178938 2016-12-26 KR101873362B1 2018-07-02 이존화; 조나탄넬시암다라; 원가연; 허진
본발명은브루셀라균 주요공통항원을발현하는비병원성약독화살모넬라균주을이용한브루셀라증예방또는치료용백신조성물에관한것이다. 본발명은브루셀라아보투스() 유래 BLS, Omp19, PrpA 및 SOD 항원의분비를증가시키도록개발된벡터로약독화살모넬라균을형질전환시키고상기형질전환된살모넬라변이주의혼합물을접종시킨마우스에서항원에대한체액성및 세포성면역반응유도및 도전감염시방어효과가우수함을확인하였다. 따라서, 본발명의변이주는안전하고경제적이며간편하게접종할수 있는브루셀라증및 살모넬라증예방또는치료용백신으로유용하게사용될것으로기대된다.
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