ZA200601689B - Process for preparing polysaccharide-protein conjugate vaccines - Google Patents
Process for preparing polysaccharide-protein conjugate vaccines Download PDFInfo
- Publication number
- ZA200601689B ZA200601689B ZA200601689A ZA200601689A ZA200601689B ZA 200601689 B ZA200601689 B ZA 200601689B ZA 200601689 A ZA200601689 A ZA 200601689A ZA 200601689 A ZA200601689 A ZA 200601689A ZA 200601689 B ZA200601689 B ZA 200601689B
- Authority
- ZA
- South Africa
- Prior art keywords
- polysaccharide
- protein
- conjugate
- activated
- conjugate vaccine
- Prior art date
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Landscapes
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US8048432B2 (en) | 2003-08-06 | 2011-11-01 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Polysaccharide-protein conjugate vaccines |
EP1651261B1 (de) | 2003-08-06 | 2014-10-08 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Polysaccharid-protein-konjugat-vakzine |
GB0500787D0 (en) | 2005-01-14 | 2005-02-23 | Chiron Srl | Integration of meningococcal conjugate vaccination |
RU2379052C2 (ru) * | 2004-04-30 | 2010-01-20 | Чирон С.Р.Л. | Вакцинация менингококковыми конъюгатами |
CN1984679B (zh) * | 2004-06-04 | 2013-05-15 | 美国政府健康及人类服务部 | 制备免疫原性结合物的方法 |
GB0502095D0 (en) | 2005-02-01 | 2005-03-09 | Chiron Srl | Conjugation of streptococcal capsular saccharides |
IL308456A (en) | 2005-04-08 | 2024-01-01 | Wyeth Llc | A multivalent pneumomuroral protein-polysaccharide conjugate preparation |
US7709001B2 (en) * | 2005-04-08 | 2010-05-04 | Wyeth Llc | Multivalent pneumococcal polysaccharide-protein conjugate composition |
US20070184072A1 (en) * | 2005-04-08 | 2007-08-09 | Wyeth | Multivalent pneumococcal polysaccharide-protein conjugate composition |
US7955605B2 (en) | 2005-04-08 | 2011-06-07 | Wyeth Llc | Multivalent pneumococcal polysaccharide-protein conjugate composition |
US8329184B2 (en) * | 2005-06-27 | 2012-12-11 | Glaxosmithkline Biologicals S.A. | Process for manufacturing vaccines |
KR101838938B1 (ko) | 2006-03-17 | 2018-03-15 | 더 거버먼트 오브 더 유나이티드 스테이츠 오브 아메리카 에즈 레프리젠티드 바이 더 세크러테리 오브 더 디파트먼트 오브 헬스 앤드 휴먼 서비시즈 | 복합 다가 면역원성 콘쥬게이트의 제조 방법 |
TW200806315A (en) | 2006-04-26 | 2008-02-01 | Wyeth Corp | Novel formulations which stabilize and inhibit precipitation of immunogenic compositions |
US8808707B1 (en) | 2006-05-08 | 2014-08-19 | Wyeth Llc | Pneumococcal dosing regimen |
EP2630972B1 (de) * | 2006-07-25 | 2017-08-30 | Lipoxen Technologies Limited | N-terminale polysialylation |
US8003112B2 (en) | 2009-04-16 | 2011-08-23 | Howard University | Meningococcal and pneumococcal conjugate vaccine and method of using same |
AU2010352695B2 (en) * | 2009-09-30 | 2014-08-21 | Glaxosmithkline Biologicals S.A. | Conjugation of Staphylococcus aureus type 5 and type 8 capsular polysaccharides |
US9173954B2 (en) | 2009-12-30 | 2015-11-03 | Glaxosmithkline Biologicals Sa | Polysaccharide immunogens conjugated to E. coli carrier proteins |
GB201003922D0 (en) | 2010-03-09 | 2010-04-21 | Glaxosmithkline Biolog Sa | Conjugation process |
CN102526724B (zh) * | 2011-01-14 | 2015-07-22 | 四川大学 | 氢氧化铝凝胶-多糖复合免疫佐剂及其制备方法和用途 |
WO2013177397A1 (en) | 2012-05-24 | 2013-11-28 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Multivalent meningococcal conjugates and methods for preparing cojugates |
EP2724730A1 (de) | 2012-10-29 | 2014-04-30 | Institut Pasteur | Glycokonjugate und deren Verwendung als potentielle Impfstoffe gegen Infektion durch Shigella flexneri |
EP2870974A1 (de) * | 2013-11-08 | 2015-05-13 | Novartis AG | Salmonella-Konjugatimpfstoffe |
US11160855B2 (en) | 2014-01-21 | 2021-11-02 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
CN105934251A (zh) * | 2014-01-21 | 2016-09-07 | 辉瑞大药厂 | 肺炎链球菌荚膜多糖及其缀合物 |
WO2015130963A2 (en) | 2014-02-27 | 2015-09-03 | Xenetic Biosciences, Inc. | Compositions and methods for administering insulin or insulin-like protein to the brain |
CN104198725B (zh) * | 2014-08-14 | 2016-04-06 | 上海睿康生物科技有限公司 | 抗环瓜氨酸肽抗体检测试剂盒 |
US9107906B1 (en) | 2014-10-28 | 2015-08-18 | Adma Biologics, Inc. | Compositions and methods for the treatment of immunodeficiency |
US10729780B2 (en) * | 2015-06-08 | 2020-08-04 | Serum Institute Of India Private Ltd. | Methods for improving the adsorption of polysaccharide-protein conjugates and multivalent vaccine formulation obtained thereof |
US20170333546A1 (en) * | 2015-12-08 | 2017-11-23 | Jl Medical Corporation | Method for Producing and Vaccine Composition of Neisseria Meningitidis Serogroups A, C, Y, and W-135 Oligosaccharides Conjugated to Glycan-Free Carrier Protein |
US11697851B2 (en) | 2016-05-24 | 2023-07-11 | The Regents Of The University Of California | Early ovarian cancer detection diagnostic test based on mRNA isoforms |
MX2019002489A (es) | 2016-09-02 | 2019-10-21 | Sanofi Pasteur Inc | Vacuna contra neisseria meningitidis. |
US10259865B2 (en) | 2017-03-15 | 2019-04-16 | Adma Biologics, Inc. | Anti-pneumococcal hyperimmune globulin for the treatment and prevention of pneumococcal infection |
KR102634811B1 (ko) | 2017-06-10 | 2024-02-06 | 인벤트프라이즈 인크. | 면역원성과 항원항체 결합성이 개선된 2가 또는 다가 접합체 다당류를 가진 다가 접합체 백신 |
US10729763B2 (en) | 2017-06-10 | 2020-08-04 | Inventprise, Llc | Mixtures of polysaccharide-protein pegylated compounds |
WO2019126197A1 (en) | 2017-12-18 | 2019-06-27 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Bacterial polysaccharide-conjugated carrier proteins and use thereof |
CN108498847A (zh) * | 2018-03-13 | 2018-09-07 | 中山大学 | 基于酰腙键的高分子水凝胶、其制备方法及皮肤组织粘附剂 |
CN108525003A (zh) * | 2018-03-13 | 2018-09-14 | 中山大学 | 基于酰腙键和亲疏水自组装的双交联杂化水凝胶、其制备方法及皮肤组织创面修复剂 |
CN109001198A (zh) * | 2018-09-03 | 2018-12-14 | 艾美卫信生物药业(浙江)有限公司 | 脱氧胆酸钠沉淀法检测Hib结合疫苗中游离多糖的方法 |
CN113274489B (zh) * | 2021-04-30 | 2023-08-29 | 山东省药学科学院 | 一种预防真菌感染的几丁质寡糖疫苗及其制备方法 |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4356170A (en) * | 1981-05-27 | 1982-10-26 | Canadian Patents & Development Ltd. | Immunogenic polysaccharide-protein conjugates |
DK163176C (da) * | 1985-09-27 | 1992-06-22 | Schweiz Serum & Impfinst | Ugiftig konjugatvaccine mod infektioner af pseudomonas aeruginosa- og escherichia coli- bakterier, fremgangsmaade til fremstilling heraf og anvendelse af vaccinen |
JPS63295408A (ja) * | 1987-05-28 | 1988-12-01 | Mitsubishi Gas Chem Co Inc | 水加ヒドラジン水溶液の精製方法 |
US5066408A (en) * | 1990-03-15 | 1991-11-19 | Powell Jonathan S | Means and method to treat swimming pool water |
NZ239643A (en) * | 1990-09-17 | 1996-05-28 | North American Vaccine Inc | Vaccine containing bacterial polysaccharide protein conjugate and adjuvant (c-nd-che-a-co-b-r) with a long chain alkyl group. |
US5480643A (en) * | 1991-10-16 | 1996-01-02 | Ecolab Inc. | Stable antimicrobial dialdehyde composition and methods of use |
US5849301A (en) * | 1993-09-22 | 1998-12-15 | Henry M. Jackson Foundation For The Advancement Of Military Medicine | Producing immunogenic constructs using soluable carbohydrates activated via organic cyanylating reagents |
US5565204A (en) | 1994-08-24 | 1996-10-15 | American Cyanamid Company | Pneumococcal polysaccharide-recombinant pneumolysin conjugate vaccines for immunization against pneumococcal infections |
NZ304715A (en) | 1995-03-22 | 1999-07-29 | Jackson H M Found Military Med | Production of immunogenic constructs using organic cyanylating reagents to activate carbohydrates and then coupling the carbohydrate to a protein, peptide or hapten |
US20020054884A1 (en) * | 1995-06-23 | 2002-05-09 | Smithkline Beecham Biologicals, Sa | Vaccine composition comprising a polysaccharide conjugate antigen adsorbed onto aluminium phosphate |
US5965714A (en) * | 1997-10-02 | 1999-10-12 | Connaught Laboratories, Inc. | Method for the covalent attachment of polysaccharides to protein molecules |
EP1315699B1 (de) * | 2000-03-22 | 2013-01-02 | Solulink, Incorporated | Hydrazin- und carbonyl-basierte bifunktionelle vernetzungsmittel |
US20050014037A1 (en) * | 2002-12-04 | 2005-01-20 | Chris Boyer | Fuel cell with recombination catalyst |
EP1651261B1 (de) | 2003-08-06 | 2014-10-08 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Polysaccharid-protein-konjugat-vakzine |
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