JP2006143729A - 非毒性の粘膜アジュバント - Google Patents
非毒性の粘膜アジュバント Download PDFInfo
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- JP2006143729A JP2006143729A JP2005335023A JP2005335023A JP2006143729A JP 2006143729 A JP2006143729 A JP 2006143729A JP 2005335023 A JP2005335023 A JP 2005335023A JP 2005335023 A JP2005335023 A JP 2005335023A JP 2006143729 A JP2006143729 A JP 2006143729A
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Abstract
【解決手段】非毒性の粘膜アジュバントを第2の抗原とともに混合して含有する薬学的組成物であって、1つの実施形態において、項上述の非毒性の粘膜アジュバントが細菌のADPリボシル化毒素の無毒化された変異体である、組成物であって、別の実施形態においいて、上述の非毒性の粘膜アジュバントがCTまたはLTの無毒化された変異体である、組成物。
【選択図】 なし
Description
本発明は、生物にワクチンを投与するために有用なアジュバントに関する。特に、本発明のアジュバントは、ワクチンを粘膜表面へ送達し、分泌応答および全身的免疫応答を誘起させ得る。
現在のワクチン接種技術は、大部分が専ら全身的なワクチン接種技術に基づいている。この技術では、ワクチンは、ワクチン接種される被験体に注射される。特定の生/弱毒化ワクチン(例えば、セービンポリオワクチン)が経口服用され得るのみである。
(項目1)非毒性の粘膜アジュバントを第2の抗原とともに混合して含有する薬学的組成物。
(項目2) 項目1に記載の組成物であって、前記非毒性の粘膜アジュバントが細菌のADPリボシル化毒素の無毒化された変異体である、組成物。
(項目3) 項目2に記載の組成物であって、前記非毒性の粘膜アジュバントがCTまたはLTの無毒化された変異体である、組成物。
(項目4) 項目2または3に記載の組成物であって、前記非毒性の粘膜アジュバントが、1またはそれより多いアミノ酸の付加、欠失、または置換を、ホロトキシンのAサブユニットに含有する、組成物。
(項目5) 前記非毒性の粘膜アジュバントがLTK7である、項目4に記載の組成物。
(項目6) 項目2から5のいずれかに定義される非毒性の変異体の、粘膜投与のための組成物の調製における粘膜アジュバントとしての使用。
(項目7) 前記組成物がワクチンである、項目6に記載の使用。
(項目8) 前記ワクチンが、予防または治療適用での使用のためである、項目7に記載の使用。
(項目9) 前記組成物がさらに第2の抗原を含有する、項目6から8のいずれかに記載の使用。
(項目10) 被験体の疾患を防止または処置するための方法であって、該被験体に、項目2から5のいずれかに定義される非毒性の変異体とともにアジュバント化した免疫学的有効量の抗原を、該被験体の粘膜表面と該アジュバント化抗原とを接触させることにより投与する工程を包含する、方法。
(項目11) 項目10に記載の方法であって、項目1から5のいずれかに記載の組成物の投与を包含する、方法。
(項目12) 前記アジュバント化抗原が、経口または鼻内に投与される、項目10または11に記載の方法。
(項目13) 同時に別々に、または連続して投与するための非毒性の粘膜アジュバントおよび第2の抗原。
(項目14) 単一の媒体、キャリア、または粒子中に組み合わせて同時に投与するための非毒性の粘膜アジュバントおよび第2の抗原。
(項目15) アジュバント化ワクチンを製造するための方法であって、
a)毒素を無毒化するために、部位特異的変異誘発を、細菌のADPリボシル化毒素のAサブユニットに行う、工程;および
b)粘膜アジュバントとして機能するように、該無毒化された毒素を、第2の抗原と結合させる工程、
を包含する、方法。
発明の要旨
従って、経口または鼻内のような粘膜表面に投与された場合、抗原の免疫原性を増大させるために使用され得る活性な粘膜アジュバントの必要が残されたままである。
a)毒素を無毒化するために、細菌のADPリボシル化毒素のAサブユニットにおいて、部位特異的変異誘発を行う工程;および
b)粘膜アジュバントとして機能させるように、無毒化した毒素を第2の抗原と結合させる工程。
細胞結合活性を有するホロトキシンとしてなおも組み合わせ得る、非毒性のLT変異体を構築するために、部位特異的変異誘発を用いて、LTのAサブユニットの7位のアルギニン残基をリジンで置換した。LTK7と名付けた、変異タンパク質を精製し、そしていくつかのアッセイでADP-リボシルトランスフェラーゼおよび毒性活性について試験した。LTK7は、なおもGM1ガングリオシドレセプターを結合し得たが、出版されたデータと一致して、酵素活性の完全な消失を示した(Lobetら,Infect.Immun. 1991; 59: 2870-2879)。さらに、LTK7は、野生型のLTの107毒性単位と同等の用量を試験した場合でさえ、マウスの回腸係蹄アッセイおよびY1細胞におけるインビトロで不活性であった(表1)。
表1
** この研究
>> 表に示す最高濃度で試験した場合に、LT-K7がなおも酵素学的に非活性または非毒性であったことを意味する。
<< 実際の差違は、示した数よりも大きいことを示し、この数は試験した差違を表す。
Claims (1)
- 薬学的組成物。
Applications Claiming Priority (2)
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GB939326174A GB9326174D0 (en) | 1993-12-22 | 1993-12-22 | Mucosal adjuvant |
IB9400068 | 1994-03-24 |
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JP51730095A Division JP4283889B2 (ja) | 1993-12-22 | 1994-12-22 | 非毒性の粘膜アジュバント |
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JP51730095A Expired - Fee Related JP4283889B2 (ja) | 1993-12-22 | 1994-12-22 | 非毒性の粘膜アジュバント |
JP2005335023A Withdrawn JP2006143729A (ja) | 1993-12-22 | 2005-11-18 | 非毒性の粘膜アジュバント |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9513371D0 (en) * | 1995-06-30 | 1995-09-06 | Biocine Spa | Immunogenic detoxified mutant toxins |
ATE275970T1 (de) | 1993-10-05 | 2004-10-15 | Celltech Pharmaceuticals Ltd | Impfstoffzusammensetzungen |
GB9326174D0 (en) | 1993-12-22 | 1994-02-23 | Biocine Sclavo | Mucosal adjuvant |
JP5148577B2 (ja) * | 1993-12-22 | 2013-02-20 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス エスアールエル | 非毒性の粘膜アジュバント |
US6436407B1 (en) | 1994-08-26 | 2002-08-20 | The Administrators Of The Tulane Educational Fund | Mutant enterotoxin effective as a non-toxic adjuvant |
US6019982A (en) * | 1994-08-26 | 2000-02-01 | The Administrators Of The Tulane Educational Fund | Mutant enterotoxin effective as a non-toxic oral adjuvant |
GB9603314D0 (en) * | 1996-02-16 | 1996-04-17 | Biocine Spa | Immunogenic detoxified mutant toxins |
US20070043215A1 (en) * | 1996-08-27 | 2007-02-22 | Heath David G | Recombinant f1-v plague vaccine |
GB9622660D0 (en) | 1996-10-31 | 1997-01-08 | Biocine Spa | Immunogenic detoxified mutant toxin |
US20060002949A1 (en) | 1996-11-14 | 2006-01-05 | Army Govt. Of The Usa, As Rep. By Secretary Of The Office Of The Command Judge Advocate, Hq Usamrmc. | Transcutaneous immunization without heterologous adjuvant |
CN101002727A (zh) * | 1996-11-14 | 2007-07-25 | (由国防部长代表的)美利坚合众国政府 | 经皮免疫之佐剂 |
US5980898A (en) * | 1996-11-14 | 1999-11-09 | The United States Of America As Represented By The U.S. Army Medical Research & Material Command | Adjuvant for transcutaneous immunization |
US6818222B1 (en) | 1997-03-21 | 2004-11-16 | Chiron Corporation | Detoxified mutants of bacterial ADP-ribosylating toxins as parenteral adjuvants |
US6824793B1 (en) | 1998-06-01 | 2004-11-30 | Chiron Corporation | Use of hyaluronic acid polymers for mucosal delivery of vaccine antigens and adjuvants |
CA2332455C (en) * | 1998-06-01 | 2012-08-14 | Chiron Corporation | Use of hyaluronic acid polymers for mucosal delivery of vaccine antigens and adjuvants |
CA2335487A1 (en) | 1998-06-19 | 1999-12-23 | Merieux Oravax | Lt and ct in parenteral immunization methods against helicobacter infection |
US6686339B1 (en) | 1998-08-20 | 2004-02-03 | Aventis Pasteur Limited | Nucleic acid molecules encoding inclusion membrane protein C of Chlamydia |
US6693087B1 (en) | 1998-08-20 | 2004-02-17 | Aventis Pasteur Limited | Nucleic acid molecules encoding POMP91A protein of Chlamydia |
EP1105490A1 (en) | 1998-08-20 | 2001-06-13 | Aventis Pasteur Limited | Nucleic acid molecules encoding inclusion membrane protein c of chlamydia |
KR100649286B1 (ko) * | 1998-10-21 | 2006-11-24 | 샤단호칭키타사토겐큐쇼 | 감독화톡신을 포함하는 백신제제 |
ATE481108T1 (de) * | 1999-02-26 | 2010-10-15 | Novartis Vaccines & Diagnostic | Verwendung von bioadhaesiven und adjuvantien für die mukosale anwendung von antigenen |
US7115730B1 (en) | 1999-04-27 | 2006-10-03 | Chiron Srl | Immunogenic detoxified mutant E. coli LT-A-toxin |
US7384640B1 (en) | 1999-09-30 | 2008-06-10 | Wyeth Holdings Corporation | Mutant cholera holotoxin as an adjuvant |
AU1013701A (en) | 1999-10-22 | 2001-05-08 | Aventis Pasteur Limited | Modified gp100 and uses thereof |
JP2003171291A (ja) * | 1999-10-29 | 2003-06-17 | Takeda Schering-Plough Animal Health Kk | 乳房炎用粘膜予防剤 |
WO2001049317A2 (en) * | 2000-01-05 | 2001-07-12 | Aventis Pasteur Limited | Enhancing the immune response to an antigen by presensitizing with an inducing agent prior to immunizing with the inducing agent and the antigen |
EP1792995A3 (en) | 2000-05-08 | 2007-06-13 | Sanofi Pasteur Limited | Chlamydia secretory locus orf and uses thereof |
AU5810201A (en) | 2000-05-10 | 2001-11-20 | Aventis Pasteur | Immunogenic polypeptides encoded by mage minigenes and uses thereof |
US7063852B2 (en) | 2000-05-19 | 2006-06-20 | The Administrators Of The Tulane Educational Fund | Hybrid LT-A/CT-B holotoxin for use as an adjuvant |
US7364739B2 (en) | 2000-08-25 | 2008-04-29 | National Research Council Of Canada | Haemophilus influenzae lipopolysaccharide inner-core oligosaccharide epitopes as vaccines for the prevention of Haemophilus influenzae infections |
DE60239317D1 (de) | 2001-01-12 | 2011-04-14 | Novartis Vaccines & Diagnostic | Nukleinsäure mukosale immunisierung |
GB0108024D0 (en) | 2001-03-30 | 2001-05-23 | Chiron Spa | Bacterial toxins |
ES2533085T3 (es) | 2001-05-22 | 2015-04-07 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Desarrollo de mutaciones útiles para atenuar virus del dengue y virus del dengue quiméricos |
IL159209A0 (en) | 2001-06-07 | 2004-06-01 | Wyeth Corp | Mutant forms of cholera holotoxin as an adjuvant |
CN1977971A (zh) | 2001-06-07 | 2007-06-13 | 惠氏控股有限公司 | 作为佐剂的霍乱全毒素的突变体形式 |
NZ536859A (en) * | 2002-05-14 | 2007-11-30 | Chiron Srl | Mucosal combination vaccines for bacterial meningitis |
GB0220205D0 (en) | 2002-08-30 | 2002-10-09 | Chiron Spa | Neisseria toxin |
JPWO2004028561A1 (ja) * | 2002-09-30 | 2006-01-19 | アステラス製薬株式会社 | 免疫応答誘導方法 |
US20050031587A1 (en) * | 2002-10-04 | 2005-02-10 | Yamanouchi Pharmaceutical Co., Ltd. | Immune response induction method |
WO2004032958A1 (en) | 2002-10-11 | 2004-04-22 | Chiron Srl | Polypeptide-vaccines for broad protection against hypervirulent meningococcal lineages |
WO2004067030A2 (en) | 2003-01-30 | 2004-08-12 | Chiron Srl | Injectable vaccines against multiple meningococcal serogroups |
GB0308198D0 (en) | 2003-04-09 | 2003-05-14 | Chiron Srl | ADP-ribosylating bacterial toxin |
GB0323103D0 (en) | 2003-10-02 | 2003-11-05 | Chiron Srl | De-acetylated saccharides |
ATE506963T1 (de) | 2003-10-02 | 2011-05-15 | Novartis Vaccines & Diagnostic | Kombinationsimpfstoffe gegen meningitis |
JP5600375B2 (ja) | 2004-03-09 | 2014-10-01 | ノバルティス バクシンズ アンド ダイアグノスティックス,インコーポレーテッド | インフルエンザウイルスワクチン |
BRPI0510315A (pt) | 2004-04-30 | 2007-10-16 | Chiron Srl | integração de vacinação com conjugado meningocócico |
GB0500787D0 (en) | 2005-01-14 | 2005-02-23 | Chiron Srl | Integration of meningococcal conjugate vaccination |
GB0409745D0 (en) | 2004-04-30 | 2004-06-09 | Chiron Srl | Compositions including unconjugated carrier proteins |
GB0410866D0 (en) | 2004-05-14 | 2004-06-16 | Chiron Srl | Haemophilius influenzae |
EP2811027A1 (en) | 2004-05-21 | 2014-12-10 | Novartis Vaccines and Diagnostics, Inc. | Alphavirus vectors for RSV and PIV vaccines |
EP2612679A1 (en) | 2004-07-29 | 2013-07-10 | Novartis Vaccines and Diagnostics, Inc. | Immunogenic compositions for gram positive bacteria such as streptococcus agalactiae |
GB0424092D0 (en) | 2004-10-29 | 2004-12-01 | Chiron Srl | Immunogenic bacterial vesicles with outer membrane proteins |
GB0502095D0 (en) | 2005-02-01 | 2005-03-09 | Chiron Srl | Conjugation of streptococcal capsular saccharides |
SI2351772T1 (sl) | 2005-02-18 | 2016-11-30 | Glaxosmithkline Biologicals Sa | Proteini in nukleinske kisline iz Escherichia coli povezane z meningitisom/sepso |
CN101203529A (zh) | 2005-02-18 | 2008-06-18 | 诺华疫苗和诊断公司 | 来自脑膜炎/脓毒症相关性大肠杆菌的蛋白质和核酸 |
EP2357000A1 (en) | 2005-10-18 | 2011-08-17 | Novartis Vaccines and Diagnostics, Inc. | Mucosal and systemic immunizations with alphavirus replicon particles |
CA2628152C (en) | 2005-11-04 | 2016-02-02 | Novartis Vaccines And Diagnostics S.R.L. | Adjuvanted vaccines with non-virion antigens prepared from influenza viruses grown in cell culture |
NZ567980A (en) * | 2005-11-04 | 2012-01-12 | Novartis Vaccines & Diagnostic | Administration routes (intranasal or mucosal and parenteral or intramuscular) for priming/boosting with influenza vaccines |
WO2007081447A2 (en) | 2005-11-22 | 2007-07-19 | Novartis Vaccines And Diagnostics, Inc. | Norovirus and sapovirus antigens |
GB0524066D0 (en) | 2005-11-25 | 2006-01-04 | Chiron Srl | 741 ii |
DK1976559T6 (da) | 2006-01-27 | 2020-04-06 | Seqirus Uk Ltd | Influenzavacciner indeholdende hæmagglutinin og matrixproteiner |
AU2007219615B2 (en) | 2006-03-03 | 2013-11-28 | Promis Neurosciences Inc. | Methods and compositions to treat and detect misfolded-SOD1 mediated diseases |
ES2536426T3 (es) | 2006-03-23 | 2015-05-25 | Novartis Ag | Compuestos de imidazoquinoxalina como inmunomoduladores |
EP2004226A1 (en) | 2006-03-24 | 2008-12-24 | Novartis Vaccines and Diagnostics GmbH & Co. KG | Storage of influenza vaccines without refrigeration |
EP2382988A1 (en) | 2006-03-31 | 2011-11-02 | Novartis AG | Combined mucosal and parenteral immunization against HIV |
US20110206692A1 (en) | 2006-06-09 | 2011-08-25 | Novartis Ag | Conformers of bacterial adhesins |
GB0614460D0 (en) | 2006-07-20 | 2006-08-30 | Novartis Ag | Vaccines |
JP2010500399A (ja) | 2006-08-16 | 2010-01-07 | ノバルティス アーゲー | 尿路病原性大腸菌由来の免疫原 |
CA2663196A1 (en) | 2006-09-11 | 2008-03-20 | Novartis Ag | Making influenza virus vaccines without using eggs |
NZ577405A (en) | 2006-12-06 | 2012-08-31 | Novartis Ag | Vaccines including antigen from four strains of influenza virus |
GB0700562D0 (en) | 2007-01-11 | 2007-02-21 | Novartis Vaccines & Diagnostic | Modified Saccharides |
CN101688194B (zh) | 2007-05-23 | 2013-09-11 | Uab研究基金会 | 去毒的肺炎球菌神经氨酸酶及其用途 |
EA201070066A1 (ru) | 2007-06-27 | 2010-06-30 | Новартис Аг | Вакцины против гриппа с низким содержанием добавок |
GB0713880D0 (en) | 2007-07-17 | 2007-08-29 | Novartis Ag | Conjugate purification |
GB0714963D0 (en) | 2007-08-01 | 2007-09-12 | Novartis Ag | Compositions comprising antigens |
AU2008299536B2 (en) | 2007-09-11 | 2014-06-12 | University Of Guelph | Novel polysaccharide immunogens from clostridium difficile |
KR101621837B1 (ko) | 2007-09-12 | 2016-05-17 | 노파르티스 아게 | Gas57 돌연변이 항원 및 gas57 항체 |
GB0810305D0 (en) | 2008-06-05 | 2008-07-09 | Novartis Ag | Influenza vaccination |
GB0818453D0 (en) | 2008-10-08 | 2008-11-12 | Novartis Ag | Fermentation processes for cultivating streptococci and purification processes for obtaining cps therefrom |
CN104292312A (zh) | 2007-12-21 | 2015-01-21 | 诺华股份有限公司 | 链球菌溶血素o的突变形式 |
NZ587382A (en) | 2008-02-21 | 2012-01-12 | Novartis Ag | Meningococcal fhbp polypeptides |
EP2268309B1 (en) | 2008-03-18 | 2015-01-21 | Novartis AG | Improvements in preparation of influenza virus vaccine antigens |
CA2743904A1 (en) * | 2008-11-17 | 2010-05-20 | The Regents Of The University Of Michigan | Cancer vaccine compositions and methods of using the same |
US8585505B2 (en) | 2008-12-15 | 2013-11-19 | Tetris Online, Inc. | Inter-game interactive hybrid asynchronous computer game infrastructure |
EP2376526A4 (en) | 2008-12-24 | 2013-02-27 | Kingdom Of The Netherlands Represented By The Min Ister Of Health Welfare & Sport On Behalf Of The M | MODIFIED STREPTOCOCCUS PNEUMONIAE PNEUMOLYSIN (PLY) POLYPEPTIDE |
AU2010203223B9 (en) | 2009-01-05 | 2015-10-08 | Epitogenesis Inc. | Adjuvant compositions and methods of use |
AU2010204139A1 (en) | 2009-01-12 | 2011-08-11 | Novartis Ag | Cna_B domain antigens in vaccines against gram positive bacteria |
US8568732B2 (en) | 2009-03-06 | 2013-10-29 | Novartis Ag | Chlamydia antigens |
PL2510947T3 (pl) | 2009-04-14 | 2016-09-30 | Kompozycje do immunizacji przeciwko Staphylococcus aureus | |
EP2442826B1 (en) | 2009-06-15 | 2015-07-08 | National University of Singapore | Influenza vaccine, composition, and methods of use |
SG177533A1 (en) | 2009-07-07 | 2012-02-28 | Novartis Ag | Conserved escherichia coli immunogens |
DK3178490T3 (da) | 2009-07-15 | 2022-06-20 | Glaxosmithkline Biologicals Sa | RSV F-proteinsammensætninger og fremgangsmåder til fremstilling af disse |
CN102770443A (zh) | 2009-07-16 | 2012-11-07 | 诺华有限公司 | 脱毒大肠杆菌免疫原 |
WO2011024072A2 (en) | 2009-08-27 | 2011-03-03 | Novartis Ag | Hybrid polypeptides including meningococcal fhbp sequences |
CN102695523A (zh) | 2009-09-10 | 2012-09-26 | 诺华有限公司 | 针对呼吸道疾病的组合疫苗 |
GB0917003D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Purification of bacterial vesicles |
GB0917002D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Improved shigella blebs |
CA2779798C (en) | 2009-09-30 | 2019-03-19 | Novartis Ag | Conjugation of staphylococcus aureus type 5 and type 8 capsular polysaccharides |
AU2010302344A1 (en) | 2009-09-30 | 2012-04-26 | Novartis Ag | Expression of meningococcal fhbp polypeptides |
GB0918392D0 (en) | 2009-10-20 | 2009-12-02 | Novartis Ag | Diagnostic and therapeutic methods |
BR112012010531A2 (pt) | 2009-10-27 | 2019-09-24 | Novartis Ag | "polipeptídeos de modificação meningocócica fhbp" |
GB0919690D0 (en) | 2009-11-10 | 2009-12-23 | Guy S And St Thomas S Nhs Foun | compositions for immunising against staphylococcus aureus |
WO2011080595A2 (en) | 2009-12-30 | 2011-07-07 | Novartis Ag | Polysaccharide immunogens conjugated to e. coli carrier proteins |
GB201003333D0 (en) | 2010-02-26 | 2010-04-14 | Novartis Ag | Immunogenic proteins and compositions |
EP3187585A1 (en) | 2010-03-25 | 2017-07-05 | Oregon Health&Science University | Cmv glycoproteins and recombinant vectors |
GB201005625D0 (en) | 2010-04-01 | 2010-05-19 | Novartis Ag | Immunogenic proteins and compositions |
WO2011127316A1 (en) | 2010-04-07 | 2011-10-13 | Novartis Ag | Method for generating a parvovirus b19 virus-like particle |
EP2558069A1 (en) | 2010-04-13 | 2013-02-20 | Novartis AG | Benzonapthyridine compositions and uses thereof |
GB201009861D0 (en) | 2010-06-11 | 2010-07-21 | Novartis Ag | OMV vaccines |
US20130171185A1 (en) | 2010-07-06 | 2013-07-04 | Ethan Settembre | Norovirus derived immunogenic compositions and methods |
US9192661B2 (en) | 2010-07-06 | 2015-11-24 | Novartis Ag | Delivery of self-replicating RNA using biodegradable polymer particles |
GB201101665D0 (en) | 2011-01-31 | 2011-03-16 | Novartis Ag | Immunogenic compositions |
GB201017519D0 (en) | 2010-10-15 | 2010-12-01 | Novartis Vaccines Inst For Global Health S R L | Vaccines |
WO2012072769A1 (en) | 2010-12-01 | 2012-06-07 | Novartis Ag | Pneumococcal rrgb epitopes and clade combinations |
EP2655389A2 (en) | 2010-12-24 | 2013-10-30 | Novartis AG | Compounds |
EP3527224A1 (en) | 2011-01-26 | 2019-08-21 | GlaxoSmithKline Biologicals S.A. | Rsv immunization regimen |
EP2668201A2 (en) | 2011-01-28 | 2013-12-04 | Sanofi Pasteur SA | Immunological compositions comprising hiv gp41 polypeptide derivatives |
PT2707385T (pt) | 2011-05-13 | 2017-12-19 | Glaxosmithkline Biologicals Sa | Antigénios de f de rsv pré-fusão |
DK2691530T3 (en) | 2011-06-10 | 2018-05-22 | Univ Oregon Health & Science | CMV GLYCOPROTEIN AND RECOMBINANT VECTORS |
BR112013032410A2 (pt) | 2011-06-24 | 2017-01-17 | Epitogenesis Inc | composições farmacêuticas compreendendo uma combinação de veículos, vitaminas, taninos e flavonoides de seleção como imunomoduladores específicos de antígeno |
CA2841047A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Immunogenic compositions and uses thereof |
EP3854413A1 (en) | 2011-07-06 | 2021-07-28 | GlaxoSmithKline Biologicals SA | Immunogenic combination compositions and uses thereof |
WO2013009564A1 (en) | 2011-07-08 | 2013-01-17 | Novartis Ag | Tyrosine ligation process |
EP2736921B1 (en) | 2011-07-25 | 2018-06-27 | GlaxoSmithKline Biologicals SA | Compositions and methods for assessing functional immunogenicity of parvovirus vaccines |
EP2568289A3 (en) | 2011-09-12 | 2013-04-03 | International AIDS Vaccine Initiative | Immunoselection of recombinant vesicular stomatitis virus expressing hiv-1 proteins by broadly neutralizing antibodies |
WO2013038375A2 (en) | 2011-09-14 | 2013-03-21 | Novartis Ag | Methods for making saccharide-protein glycoconjugates |
WO2013038385A2 (en) | 2011-09-14 | 2013-03-21 | Novartis Ag | Escherichia coli vaccine combination |
EP2586461A1 (en) | 2011-10-27 | 2013-05-01 | Christopher L. Parks | Viral particles derived from an enveloped virus |
AU2012335208B2 (en) | 2011-11-07 | 2017-08-31 | Glaxosmithkline Biologicals S.A. | Carrier molecule comprising a spr0096 and a spr2021 antigen |
WO2013108272A2 (en) | 2012-01-20 | 2013-07-25 | International Centre For Genetic Engineering And Biotechnology | Blood stage malaria vaccine |
JP2015518845A (ja) | 2012-05-22 | 2015-07-06 | ノバルティス アーゲー | 髄膜炎菌血清群xコンジュゲート |
EP2679596B1 (en) | 2012-06-27 | 2017-04-12 | International Aids Vaccine Initiative | HIV-1 env glycoprotein variant |
EP2869842A1 (en) | 2012-07-06 | 2015-05-13 | Novartis AG | Immunogenic compositions and uses thereof |
MX363529B (es) | 2012-09-18 | 2019-03-27 | Novartis Ag | Vesículas de membrana externa. |
EA201590427A1 (ru) | 2012-10-02 | 2015-09-30 | Глаксосмитклайн Байолоджикалс С.А. | Нелинейные сахаридные конъюгаты |
US9855324B2 (en) | 2012-10-03 | 2018-01-02 | Glaxosmithkline Biologicals Sa | Immunogenic compositions |
ES2826555T3 (es) | 2012-11-30 | 2021-05-18 | Glaxosmithkline Biologicals Sa | Antígenos de Pseudomonas y combinación de antígenos |
CN105188747A (zh) | 2013-02-01 | 2015-12-23 | 葛兰素史密斯克莱生物公司 | 包含toll样受体激动剂的免疫组合物的皮内递送 |
WO2014140938A2 (en) | 2013-03-14 | 2014-09-18 | Centre Hospitalier Universitaire Vaudois | Immunological methods |
EP2848937A1 (en) | 2013-09-05 | 2015-03-18 | International Aids Vaccine Initiative | Methods of identifying novel HIV-1 immunogens |
EP2873423B1 (en) | 2013-10-07 | 2017-05-31 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
EP2870974A1 (en) | 2013-11-08 | 2015-05-13 | Novartis AG | Salmonella conjugate vaccines |
LT3122378T (lt) | 2014-03-26 | 2020-02-10 | Glaxosmithkline Biologicals S.A. | Mutantų stafilokokiniai antigenai |
US10174292B2 (en) | 2015-03-20 | 2019-01-08 | International Aids Vaccine Initiative | Soluble HIV-1 envelope glycoprotein trimers |
EP3072901A1 (en) | 2015-03-23 | 2016-09-28 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
CN108350051A (zh) | 2015-11-09 | 2018-07-31 | 英属哥伦比亚大学 | 淀粉样蛋白β中的N-末端表位及其构象选择性抗体 |
KR20180085736A (ko) | 2015-11-09 | 2018-07-27 | 더 유니버시티 오브 브리티쉬 콜롬비아 | 아밀로이드 베타 중간-영역 내 에피토프 및 이에 대해 구조적으로 선택성인 항체 |
WO2017079835A1 (en) | 2015-11-09 | 2017-05-18 | The University Of British Columbia | Amyloid beta epitopes and antibodies thereto |
US20180125920A1 (en) | 2016-11-09 | 2018-05-10 | The University Of British Columbia | Methods for preventing and treating A-beta oligomer-associated and/or -induced diseases and conditions |
IT201900007060A1 (it) | 2019-05-21 | 2020-11-21 | St Superiore Di Sanita | Cellule tumorali ingegnerizzate e loro usi |
IT201900012540A1 (it) | 2019-07-22 | 2021-01-22 | Humanitas Mirasole Spa | Inibitori di CHI3L1 e loro usi |
EP4114848A4 (en) | 2020-02-26 | 2024-04-03 | Versitech Limited | PD-1-BASED VACCINES AGAINST CORONAVIRUS INFECTION |
Family Cites Families (63)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4328209A (en) * | 1979-04-11 | 1982-05-04 | Board Of Regents, The University Of Texas System | Cholera vaccine |
US4428931A (en) * | 1982-03-15 | 1984-01-31 | Merck & Co., Inc. | Bacterial toxoids and gram-negative immune globulin therefrom |
US4666837A (en) * | 1982-05-24 | 1987-05-19 | Smithkline-Rit | DNA sequences, recombinant DNA molecules and processes for producing the A and B subunits of cholera toxin and preparations containing so-obtained subunit or subunits |
CH660375A5 (it) * | 1983-02-08 | 1987-04-15 | Sclavo Spa | Procedimento per la produzione di proteine correlate alla tossina difterica. |
US5882653A (en) * | 1983-03-04 | 1999-03-16 | The University Of Maryland System | Vibrio cholerae 01 (CVD111) and non-01 (CVD112 and CVD112RM) serogroup vaccine strains, methods of making same and products thereof |
US5668255A (en) * | 1984-06-07 | 1997-09-16 | Seragen, Inc. | Hybrid molecules having translocation region and cell-binding region |
CA1340373C (en) * | 1986-01-28 | 1999-02-02 | Rino Rappuoli | Cloning and sequencing of the dna fragment which codes for the five subunits of the pertussis toxin, a hybrid plasmid containing the dna fragment and micro-organisms transformed by the hybrid plasmid and capable of expressing all or some of the subunits of the pertussis toxin |
US5032398A (en) * | 1986-08-01 | 1991-07-16 | Kaslow Harvey R | Selective modification of the catalytic subunit of pertussis toxin |
US4892827A (en) * | 1986-09-24 | 1990-01-09 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant pseudomonas exotoxins: construction of an active immunotoxin with low side effects |
WO1989001976A1 (en) * | 1987-09-04 | 1989-03-09 | Amgen Inc. | Recombinant dna-derived bordetella toxin subunit analogs |
US5925546A (en) * | 1987-11-02 | 1999-07-20 | Chiron S.P.A. | Immunologically active polypeptides with altered toxicity useful for the preparation of an antipertussis vaccine |
US6713072B1 (en) * | 1987-11-02 | 2004-03-30 | Chiron S.R.L. | Immunologically active polypeptides with altered toxicity useful for the preparation of an antipertussis vaccine |
GB8727489D0 (en) * | 1987-11-24 | 1987-12-23 | Connaught Lab | Detoxification of pertussis toxin |
US5358868A (en) * | 1987-11-24 | 1994-10-25 | Connaught Laboratories Limited | Genetic detoxification of pertussis toxin |
US5244657A (en) * | 1987-11-24 | 1993-09-14 | Connaught Laboratories Limited | Genetic detoxification of pertussis toxin |
US5221618A (en) * | 1987-11-24 | 1993-06-22 | Connaught Laboratories Limited | Genetic detoxification of pertussis toxin |
US5332583A (en) * | 1987-11-24 | 1994-07-26 | Connaught Laboratories Limited | Vaccine containing genetically-detoxified pertussis holotoxin |
JP2849632B2 (ja) * | 1988-04-08 | 1999-01-20 | 社団法人北里研究所 | ワクチン製剤 |
US5211657A (en) * | 1988-11-07 | 1993-05-18 | The United States Government As Represented By The Secretary Of The Department Of Health And Human Services | Laminin a chain deduced amino acid sequence, expression vectors and active synthetic peptides |
WO1990006366A1 (en) * | 1988-12-07 | 1990-06-14 | University Of Leicester | Heat-labile toxin b subunit fusion proteins |
DK0396964T3 (da) * | 1989-04-28 | 1995-10-30 | Sclavo Spa | Pertussistoxin-mutanter, Bordetella-stammer, der er i stand til at producere sådanne mutanter, samt deres anvendelse til udvikling af antipertussis-vacciner |
US5786189A (en) * | 1989-11-29 | 1998-07-28 | Smithkline Beecham Biologicals (S.A.) | Vaccine |
IT1248735B (it) * | 1990-06-21 | 1995-01-26 | Sclavo Spa | Vaccini acellulari contro la pertosse |
US5241053A (en) * | 1990-09-05 | 1993-08-31 | Takeda Chemical Industries, Ltd. | Fused proteins comprising glycoprotein gD of HSV-1 and LTB |
IL101715A (en) * | 1991-05-02 | 2005-06-19 | Amgen Inc | Recombinant dna-derived cholera toxin subunit analogs |
GB9513371D0 (en) * | 1995-06-30 | 1995-09-06 | Biocine Spa | Immunogenic detoxified mutant toxins |
IT1253009B (it) * | 1991-12-31 | 1995-07-10 | Sclavo Ricerca S R L | Mutanti immunogenici detossificati della tossina colerica e della tossina lt, loro preparazione ed uso per la preparazione di vaccini |
US20020044939A1 (en) * | 1991-12-31 | 2002-04-18 | Chiron S.P.A. | Immunogenic detoxified mutants of cholera toxin |
US5874088A (en) * | 1992-07-06 | 1999-02-23 | President And Fellows Of Harvard College | Deletion mutants of cholera vaccines expressing heterologous antigens |
CA2156191A1 (en) * | 1993-02-22 | 1994-09-01 | Stephen B. Calderwood | Heterologous antigens in live cell vaccine strains |
KR100333113B1 (ko) * | 1993-07-27 | 2002-11-27 | 시에스엘 리미티드 | 헬리코박터피롤리관련위십이지장질환의치료방법 |
US5856122A (en) * | 1993-08-24 | 1999-01-05 | University Of Alberta | Modification of pertussis toxin |
ATE275970T1 (de) * | 1993-10-05 | 2004-10-15 | Celltech Pharmaceuticals Ltd | Impfstoffzusammensetzungen |
US5961970A (en) * | 1993-10-29 | 1999-10-05 | Pharmos Corporation | Submicron emulsions as vaccine adjuvants |
GB9326174D0 (en) * | 1993-12-22 | 1994-02-23 | Biocine Sclavo | Mucosal adjuvant |
US20030072774A1 (en) * | 1994-06-10 | 2003-04-17 | Diane M. Gajewczyk | Proteinaceous adjuvants |
US6436407B1 (en) * | 1994-08-26 | 2002-08-20 | The Administrators Of The Tulane Educational Fund | Mutant enterotoxin effective as a non-toxic adjuvant |
US6019982A (en) * | 1994-08-26 | 2000-02-01 | The Administrators Of The Tulane Educational Fund | Mutant enterotoxin effective as a non-toxic oral adjuvant |
US5932714A (en) * | 1995-02-23 | 1999-08-03 | Connaught Laboratories Limited | Expression of gene products from genetically manipulated strains of Bordetella |
GB9513733D0 (en) * | 1995-07-05 | 1995-09-06 | Univ Bristol | Therapeutic agents |
US6030624A (en) * | 1996-08-16 | 2000-02-29 | Uab Research Foundation | Mucosal immunogens for novel vaccines |
GB9622660D0 (en) * | 1996-10-31 | 1997-01-08 | Biocine Spa | Immunogenic detoxified mutant toxin |
US5908825A (en) * | 1997-01-09 | 1999-06-01 | University Of Maryland At Baltimore | Dosage composition for nasal delivery and method of use of the same |
US6818222B1 (en) * | 1997-03-21 | 2004-11-16 | Chiron Corporation | Detoxified mutants of bacterial ADP-ribosylating toxins as parenteral adjuvants |
EP0919243A1 (en) * | 1997-11-25 | 1999-06-02 | Duphar International Research B.V | Vaccine containing B subunits of heat-labile enterotoxin (LTB) of Escherichia coli as an adjuvant |
AU2232399A (en) * | 1998-01-16 | 1999-08-02 | Maxim Pharmaceuticals, Inc. | Recombinant ctb-based vaccines |
US6033673A (en) * | 1998-03-18 | 2000-03-07 | The Administrators Of Tulane Educational Fund | Double mutant enterotoxin for use as an adjuvant |
GB9808932D0 (en) * | 1998-04-27 | 1998-06-24 | Chiron Spa | Polyepitope carrier protein |
WO1999057278A2 (en) * | 1998-04-30 | 1999-11-11 | Chiron S.P.A. | IMMUNIZATION AGAINST AND TREATMENT FOR INFECTION BY $i(H.PYLORI) |
HUP0104842A3 (en) * | 1998-05-08 | 2002-12-28 | Univ Bristol Bristol | Vaccine |
DK1117435T3 (da) * | 1998-09-30 | 2008-03-17 | Wyeth Corp | Muteret cholera-holotoxin som adjuvans |
BR9916515A (pt) * | 1998-12-22 | 2001-11-06 | Thompson Boyce Plant Res | Polinucleotìdeo, vetor de expressão, células de e. coli e de agrobacterium tumefaciens transformadas com o vetor de expressão, célula de planta transgênica, semente de planta transgênica, célula eucariótica transgênica, composição imunogênica, método de evocar uma resposta imune em um animal ou ser humano, planta transgênica, e, adjuvante |
US7115730B1 (en) * | 1999-04-27 | 2006-10-03 | Chiron Srl | Immunogenic detoxified mutant E. coli LT-A-toxin |
TR200103266T2 (tr) * | 1999-05-13 | 2002-01-21 | American Cyanamid Company | Yardımcı kombinasyon formülasyonları |
GB9923060D0 (en) * | 1999-09-29 | 1999-12-01 | Chiron Spa | Vaccine |
US7384640B1 (en) * | 1999-09-30 | 2008-06-10 | Wyeth Holdings Corporation | Mutant cholera holotoxin as an adjuvant |
US20040109874A1 (en) * | 1999-11-10 | 2004-06-10 | Powderject Vaccines, Inc. | Induction of mucosal immunity by vaccination via the skin route |
EE200300172A (et) * | 2000-11-10 | 2003-06-16 | Wyeth Holdings Corporation | Antigeenne kompositsioon ja adjuvantsegu |
GB0108024D0 (en) * | 2001-03-30 | 2001-05-23 | Chiron Spa | Bacterial toxins |
ES2399386T3 (es) * | 2001-04-05 | 2013-04-01 | Novartis Vaccines And Diagnostics, Inc. | Aumento de la inmunidad de las mucosas tras sensibilización parenteral |
DE602004020189D1 (de) * | 2003-01-30 | 2009-05-07 | Novartis Vaccines & Diagnostic | Adjuvante influenza-vakzine |
JP2007509164A (ja) * | 2003-10-23 | 2007-04-12 | カイロン コーポレイション | 安定化組成物 |
WO2006128296A1 (en) * | 2005-06-01 | 2006-12-07 | Sanofi Pasteur Limited | Pal-based chlamydia vaccine |
-
1993
- 1993-12-22 GB GB939326174A patent/GB9326174D0/en active Pending
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1994
- 1994-12-22 AT AT95903889T patent/ATE187078T1/de active
- 1994-12-22 AU AU12785/95A patent/AU1278595A/en not_active Abandoned
- 1994-12-22 DK DK95903889T patent/DK0732937T4/da active
- 1994-12-22 PT PT95903889T patent/PT732937E/pt unknown
- 1994-12-22 EP EP95903889A patent/EP0732937B2/en not_active Expired - Lifetime
- 1994-12-22 WO PCT/IB1995/000013 patent/WO1995017211A1/en active IP Right Grant
- 1994-12-22 JP JP51730095A patent/JP4283889B2/ja not_active Expired - Fee Related
- 1994-12-22 ES ES95903889T patent/ES2139879T5/es not_active Expired - Lifetime
- 1994-12-22 DE DE69421939T patent/DE69421939T3/de not_active Expired - Lifetime
- 1994-12-22 CA CA002179771A patent/CA2179771C/en not_active Expired - Fee Related
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2000
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2002
- 2002-06-04 US US10/163,448 patent/US20020187154A1/en not_active Abandoned
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2003
- 2003-01-24 US US10/351,075 patent/US7070781B2/en not_active Expired - Fee Related
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2005
- 2005-11-18 JP JP2005335023A patent/JP2006143729A/ja not_active Withdrawn
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2006
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CA2179771A1 (en) | 1995-06-29 |
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GR3032497T3 (en) | 2000-05-31 |
PT732937E (pt) | 2000-05-31 |
DE69421939T3 (de) | 2009-11-05 |
US7485304B2 (en) | 2009-02-03 |
ES2139879T5 (es) | 2009-06-10 |
DK0732937T3 (da) | 2000-05-01 |
AU1278595A (en) | 1995-07-10 |
EP0732937A1 (en) | 1996-09-25 |
ES2139879T3 (es) | 2000-02-16 |
DK0732937T4 (da) | 2009-06-08 |
ATE187078T1 (de) | 1999-12-15 |
US20040028690A1 (en) | 2004-02-12 |
CA2179771C (en) | 2001-02-20 |
DE69421939D1 (de) | 2000-01-05 |
JPH10500099A (ja) | 1998-01-06 |
DE69421939T2 (de) | 2000-06-15 |
EP0732937B1 (en) | 1999-12-01 |
US20020187154A1 (en) | 2002-12-12 |
WO1995017211A1 (en) | 1995-06-29 |
EP0732937B2 (en) | 2009-03-18 |
JP4283889B2 (ja) | 2009-06-24 |
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