JPH09501933A - 植物、動物、およびヒトのワクチンとして並びに免疫療法に有用な抗体の免疫優性エピトープの弱化 - Google Patents
植物、動物、およびヒトのワクチンとして並びに免疫療法に有用な抗体の免疫優性エピトープの弱化Info
- Publication number
- JPH09501933A JPH09501933A JP7507666A JP50766695A JPH09501933A JP H09501933 A JPH09501933 A JP H09501933A JP 7507666 A JP7507666 A JP 7507666A JP 50766695 A JP50766695 A JP 50766695A JP H09501933 A JPH09501933 A JP H09501933A
- Authority
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- Japan
- Prior art keywords
- vaccine
- epitope
- amino acids
- modified
- immunodominant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.哺乳類に投与して該哺乳類内に病原性有機体に対する免疫的防除を引 き起こし得るワクチンであって、前記病原性有機体は免疫優性エピトープを有す る抗原を含み、当該ワクチンは前記免疫優性エピトープが免疫弱化された前記抗 原の修飾形態物と薬学的に許容される担体とを含むワクチン。 2.天然抗原または、当該ワクチンは前記天然抗原をコードしてこの天然 抗原を前記哺乳類中に発現するベクターを更に含む請求の範囲第1項に記載のワ クチン。 3.ヒトに投与して被験者内でHIV−1に対する免疫的防除を引き起こ し得るワクチンであって、前記ワクチンはHIV−1のgp120/160の修 飾形態物と、前記ヒトに投与するための薬学的に許容される担体とを含み、ここ で、前記gp120/160のV3ループは免疫弱化されたものである請求の範 囲第1項に記載のワクチン。 4.前記V3ループは天然V3ループには存在しない一以上のN−結合グ リコシル化シグナルを含む修飾アミノ酸配列を有する請求の範囲第3項に記載の ワクチン。 5.前記担体は薬学的に許容される生理食塩緩衝液を含むものである、請 求の範囲第1項に記載のワクチン。 6.前記免疫優性エピトープはこのエピトープに対する炭水化物部分の付 加によって免疫弱化されたものである、請求の範囲第1項に記載のワクチン。 7.前記免疫優性エピトープは複数のアミノ酸を含み、前記エピトープは このアミノ酸の改変によって免疫弱化される、請求の範囲第1項に記載のワクチ ン。 8.前記改変はアミノ酸置換を包含するものである、請求の範囲第7項に 記載のワクチン。 9.前記複数のアミノ酸はヒトB細胞に寛容化された異なる複数のアミノ 酸によって置換されたものである、請求の範囲第8項に記載のワクチン。 10.前記異なる複数のアミノ酸は直鎖状のヒトB細胞エピトープを含む、 請求の範囲第9項に記載のワクチン。 11.前記複数のアミノ酸は生来の電荷を有し、前記改変はこの生来の電荷 の変更をもたらすものである、請求の範囲第7項に記載のワクチン。 12.前記改変は前記複数のアミノ酸の1以上の除去を含むものである、請 求の範囲第7項に記載のワクチン。 13.前記免疫優性エピトープは少なくとも1つの他の分子に対する結合部 位を含み、前記ワクチンは前記エピトープに非可逆的に結合した少なくとも1つ の他の分子をさらに含むものである、請求の範囲第1項に記載のワクチン。 14.前記他の分子は前記エピトープに対して指向する抗体を含むものであ る、請求の範囲第13項に記載のワクチン。 15.前記エピトープはレセプターを含み、前記他の分子は該レセプターに 対するリガンドを含むものである、請求の範囲第13項に記載のワクチン。 16.前記免疫優性エピトープは、前記哺乳類がこれに対する中和抗体を産 生することができるエピトープである、請求の範囲第1項に記載のワクチン。 17.前記免疫優性エピトープは複数のアミノ酸を含み、前記複数のアミノ 酸は前記病原性有機体の生存能に影響を及ぼすことなく変更されることができ、 これによって前記複数のアミノ酸が前記病原性有機体の複数の世代にわたる遺伝 子的浮動によって変化され得るものである、請求の範囲第1項に記載のワクチン 。 18.前記病原性有機体はウイルス、真菌、原虫類、および細菌から成る群 より選択されるものである、請求の範囲第1項に記載のワクチン。 19.前記病原性有機体はインフルエンザウイルスである、請求の範囲第1 8項に記載のウイルス。 20.前記病原性有機体はHIV−1であり、前記免疫優性エピトープはH IV−1のgp120/160のV3ループである、請求の範囲第1項に記載の ワクチン。 21.前記免疫優性エピトープは付加的なN−結合グリコシル化シグナルを 含むように改変された複数のアミノ酸を含むものである、請求の範囲第20項に 記載のワクチン。 22.哺乳類に投与して該哺乳類内に病原性有機体に対する免疫的防御を引 き起こすワクチンを製造する方法であって、前記病原性有機体は元々の免疫優性 エピトープを有する抗原を包含し、前記抗原は前記元来の免疫優性エピトープを 含むアミノ酸のサブセットを含む複数のアミノ酸を含み、当該方法は、 前記元々の免疫優性エピトープを含むアミノ酸の前記サブセットを包含する前 記複数のアミノ酸をコードするポリヌクレオチド配列を得ること、 前記元来の免疫優性エピトープとは異なるサブセットのアミノ酸を含む修飾さ れた免疫優性エピトープをコードするようにポリヌクレオチド配列を修飾するこ と、 前記修飾段階の結果得られた前記ポリヌクレオチド配列を発現し、これにより 、前記修飾された免疫優性エピトープを含む修飾抗原を産生して、前記修飾免疫 優性エピトープが前記元々の免疫優性エピトープと比較して相対的に免疫弱化さ れること、および 前記修飾抗原と薬学的に許容される担体とを含有するワクチン組成物を調製す ること、 の各段階を含むものである、ワクチンの製造方法。 23.前記修飾段階は、前記元来の免疫優性エピトープ内における少なくと も1つのアミノ酸置換をコードする修飾ポリヌクレオチド配列を産生することを 包含する、請求の範囲第22項に記載の方法。 24.前記修飾ポリヌクレオチド配列はヒトB細胞に寛容化される修飾免疫 優性エピトープをコードするものである、請求の範囲第23項に記載の方法。 25.前記修飾免疫優性エピトープは直鎖状のヒトB細胞エピトープである、 請求の範囲第24項に記載の方法。 26.前記元々の免疫優性エピトープを含む前記アミノ酸のサブセットは生 来の電荷を有し、前記修飾段階は前記生来の電荷とは異なる電荷を有する修飾免 疫優性エピトープをコードする修飾ポリヌクレオチド配列を産生するものである 、請求の範囲第23項に記載の方法。 27.前記修飾段階は前記元来の免疫優性エピトープ中の少なくとも1つの アミノ酸欠損をコードする修飾ポリヌクレオチド配列を産生することを包含する 、 請求の範囲第22項に記載の方法。 28.ヒトに投与してHIV−1に対する免疫防御を前記ヒトにもたらすこ とのできるワクチンの製造方法であって、本方法は、 HIV−1のgp120/160抗原を得ること、 前記gp120/160抗原をトロンビンに暴露処理してこのgp120/1 60抗原を分解すること、さらに、 上記トロンビンで処理された抗原と薬学的に許容される担体とを含むワクチン 組成物を調製すること、 の各段階を含むものである、請求の範囲第22項に記載の方法。 29.gp120/160の9238部位が処理段階の間で完全体である、 請求の範囲第28項に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US08/109,934 US5585250A (en) | 1993-08-20 | 1993-08-20 | Dampening of an immunodominant epitope of an antigen for use in plant, animal and human compositions and immunotherapies |
US08/109,934 | 1993-08-20 | ||
PCT/US1994/009336 WO1995006124A1 (en) | 1993-08-20 | 1994-08-19 | Dampening of an immunodominant epitope of an antigen for use in plant, animal and human vaccines and immunotherapies |
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JP2005367769A Division JP2006104216A (ja) | 1993-08-20 | 2005-12-21 | 植物、動物、およびヒトのワクチンとして並びに免疫療法に有用な抗体の免疫優性エピトープの弱化 |
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JPH09501933A true JPH09501933A (ja) | 1997-02-25 |
JP3851938B2 JP3851938B2 (ja) | 2006-11-29 |
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JP50766695A Expired - Lifetime JP3851938B2 (ja) | 1993-08-20 | 1994-08-19 | 植物、動物、およびヒトのワクチンとして並びに免疫療法に有用な抗体の免疫優性エピトープの弱化 |
JP2005367769A Pending JP2006104216A (ja) | 1993-08-20 | 2005-12-21 | 植物、動物、およびヒトのワクチンとして並びに免疫療法に有用な抗体の免疫優性エピトープの弱化 |
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JP2005367769A Pending JP2006104216A (ja) | 1993-08-20 | 2005-12-21 | 植物、動物、およびヒトのワクチンとして並びに免疫療法に有用な抗体の免疫優性エピトープの弱化 |
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US (2) | US5585250A (ja) |
EP (1) | EP0714444B1 (ja) |
JP (2) | JP3851938B2 (ja) |
AT (1) | ATE211767T1 (ja) |
AU (1) | AU700786B2 (ja) |
CA (2) | CA2623540A1 (ja) |
DE (1) | DE69429625T2 (ja) |
DK (1) | DK0714444T3 (ja) |
ES (1) | ES2170771T3 (ja) |
PT (1) | PT714444E (ja) |
WO (1) | WO1995006124A1 (ja) |
Cited By (1)
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JP2011513235A (ja) * | 2008-02-21 | 2011-04-28 | バイオロジカル ミメティクス インコーポレイテッド | 免疫原性インフルエンザ組成物 |
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Publication number | Priority date | Publication date | Assignee | Title |
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US5585250A (en) * | 1993-08-20 | 1996-12-17 | The United States Of America As Represented By The Department Of Health & Human Services | Dampening of an immunodominant epitope of an antigen for use in plant, animal and human compositions and immunotherapies |
ATE285417T1 (de) * | 1995-11-03 | 2005-01-15 | Binding Site Ltd | Herstellung von antikörpern |
US6835550B1 (en) * | 1998-04-15 | 2004-12-28 | Genencor International, Inc. | Mutant proteins having lower allergenic response in humans and methods for constructing, identifying and producing such proteins |
US6936249B1 (en) * | 1998-04-15 | 2005-08-30 | Genencor International, Inc. | Proteins producing an altered immunogenic response and methods of making and using the same |
US6642011B2 (en) * | 1998-04-15 | 2003-11-04 | Genencor International, Inc. | Human protease and use of such protease for pharmaceutical applications and for reducing the allergenicity of non-human proteins |
US20020182180A1 (en) * | 1998-05-29 | 2002-12-05 | Yutaro Kaneko | Method for inducing immunity to viruses |
JP2002531067A (ja) * | 1998-10-30 | 2002-09-24 | ノボザイムス アクティーゼルスカブ | 低下したアレルゲン性を有するグリコシル化タンパク質 |
US6759216B1 (en) * | 1998-11-06 | 2004-07-06 | Emory University | Glycosylated, low antigenicity low immunogenicity factor VIII |
US7078043B2 (en) | 1999-04-20 | 2006-07-18 | Medical Research Council | Malaria vaccine |
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JP2011513235A (ja) * | 2008-02-21 | 2011-04-28 | バイオロジカル ミメティクス インコーポレイテッド | 免疫原性インフルエンザ組成物 |
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DK0714444T3 (da) | 2002-04-29 |
CA2169764C (en) | 2008-04-15 |
JP2006104216A (ja) | 2006-04-20 |
CA2623540A1 (en) | 1995-03-02 |
AU700786B2 (en) | 1999-01-14 |
US5585250A (en) | 1996-12-17 |
ATE211767T1 (de) | 2002-01-15 |
EP0714444B1 (en) | 2002-01-09 |
CA2169764A1 (en) | 1995-03-02 |
JP3851938B2 (ja) | 2006-11-29 |
WO1995006124A1 (en) | 1995-03-02 |
PT714444E (pt) | 2002-07-31 |
EP0714444A1 (en) | 1996-06-05 |
ES2170771T3 (es) | 2002-08-16 |
DE69429625T2 (de) | 2002-09-12 |
US5853724A (en) | 1998-12-29 |
AU7569294A (en) | 1995-03-21 |
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