ES2541123T3 - Composición para la prevención/el tratamiento de infecciones con HBV y de enfermedades mediadas por HBV - Google Patents
Composición para la prevención/el tratamiento de infecciones con HBV y de enfermedades mediadas por HBV Download PDFInfo
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- ES2541123T3 ES2541123T3 ES04764564.3T ES04764564T ES2541123T3 ES 2541123 T3 ES2541123 T3 ES 2541123T3 ES 04764564 T ES04764564 T ES 04764564T ES 2541123 T3 ES2541123 T3 ES 2541123T3
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- hbv
- hbsag
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- JUMGSHROWPPKFX-UHFFFAOYSA-N brefeldin-A Natural products CC1CCCC=CC2(C)CC(O)CC2(C)C(O)C=CC(=O)O1 JUMGSHROWPPKFX-UHFFFAOYSA-N 0.000 description 2
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
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- C07K14/01—DNA viruses
- C07K14/02—Hepadnaviridae, e.g. hepatitis B virus
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- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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Abstract
Uso de una composición, que contiene al menos dos antígenos de superficie del virus de hepatitis B (HBsAg's), fragmentos de los mismos, que contienen un epítope de célula T, en cuyo caso los fragmentos de los al menos dos HBsAgs tienen conjuntamente al menos 10 aminoácidos, aunque en se diferencian uno de otro al menos por un aminoácido, y/o estos ácidos nucleicos codificantes, en cuyo caso los HBsAgs se componen de la proteína S (pequeño antígeno de superficie de HBV) y en cuyo caso los HBsAgs se diferencian en el genotipo del virus de hepatitis B (HBV) en la región S de HbsAg, y en cuyo caso la composición no contiene antígeno de núcleo de HBV (HBcAg) o este ácido nucleico codificante, para la producción de un medicamento para el tratamiento terapéutico de una infección con HBV o una enfermedad mediada por HBV.
Description
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E04764564
30-06-2015
Figura 10: respuestas de células T CD8+ HBsAg-específicas frente al epítope en 1 (S208-215) en ratones HBsayw-tg.
A. Los ratones HBs-tg que expresan HBsAgayw en el hígado fueron inmunizados tres veces (a intervalos de cuatro semanas) por vía intramuscular con vacunas de ADN que solamente codifican el subtipo ayw (pCI/Sayw) de HBsAg
- o los tres tipos ayw (pCI/Sayw), adw2 (pCI/Sadw2) y adr (pCI/Sadr), o con el vector de control negativo pCI (vector sin inserto). 12 días después de la última inmunización se retiró el bazo de los animales. Las células de bazo aisladas fueron re estimuladas durante un período de 4 horas in vitro (en presencia de Brefeldin A) con células RBL5 que habían sido pulsadas previamente con el péptido de enlace 1 Kb/ S208-215 de HBsAgayw (ILSPFLPL) o HBsAgadw2 (IVSPFIPL). Se muestra el número de las células T CD8+ de IFNγ+ de bazo / 105 células T CD8+ ± desviación estándar de 4-6 ratones (de dos experimentos independientes entre sí) por grupo.
- B.
- Los ratones de HBsayw-tg fueron inmunizados por vientre muscular tres veces (a intervalos de 21 días) con partículas de proteína HBsAg (SP) del subtipo ayw o una mezcla de partículas de proteína HBsAg de los subtipos ayw, adw2 y adr. A las vacunas de proteína se adicionaron respectivamente oligonucleótidos de CpG (ODN) o RC529 (mostrados solamente para la mezcla de subtipos) en calidad de adyuvantes. Como control negativo sirvió PBS. 12 días después de la última inmunización se retiró el paso de los animales. Las células de bazo aisladas se re estimularon durante un período de 4 horas in vitro (en presencia de Brefeldin A) con células RBL5, las cuales previamente habían sido pulsadas con el péptido de enlace 1 Kb/ S208-215 de HBsAgayw (ILSPFLPL) o HBsAgadw2 (IVSPFIPL). Se muestra el número de las células T CD8+ de IFNγ+ de bazo / 105 células T CD8+ ± desviación estándar de 4-6 ratones (de dos experimentos independientes entre sí) por grupo.
Figura 11: inducción de respuestas a anticuerpo de suero HBsAg -específicos en ratones HBs-tg. Ratones B6 y transgénicos HBs-tg fueron inmunizados por vía intramuscular con vacunas de partículas de proteína HBsAg (SP) del subtipo ayw o del subtipo adw2 o con una mezcla de los subtipos ayw, adw2 y adr y después de tres semanas fueron reforzados con la misma vacuna. Las vacunas de proteína contenían como aditivo CpG-oligonucleótidos (ODN) en calidad de adyuvantes. Cuatro semanas después de la inyección de refuerzo, se estudiaron las muestras de suero con relación a anticuerpos de HBsAg (A) y HBsAg-específicos (B). Se muestran los títulos medios de anticuerpo (mIU/ml) y el nivel de HBsAg en suero (ng/ml) ± desviaciones estándar de 4-6 ratones/grupo.
A continuación, la invención se ilustra por medio de ejemplos. Sin embargo, estos ejemplos no pretenden limitar la invención.
Ejemplos:
Material y métodos
Generalidades
El subtipo adw2 de HBV estudiado corresponde al genotipo A. El subtipo ayw de HBV corresponde al genotipo D. El subtipo adr de HBV corresponde al genotipo C.
Ratones
Ratones (B6) C57BL/6JBom (H-2b) fueron mantenidos en condiciones estándar libres de patógenos.
Ratones transgénicos (HBs-tg) C57BL/6J-TgN(Alb1 HBV)44Bri, HbsAgayw (codificado por la secuencia de HBV con el número de depósito V01460 J02203) fueron obtenidos del laboratorio The Jackson Laboratory (Bar Harbour, ME). Se usaron ratones machos y hembras en una edad de 8-16 semanas.
Células, partículas recombinantes de HBsAg y péptido antigénico de HBsAg
La línea celular H-2b RBL5 utilizada se describe en [10]. Fueron preparados transfectantes estables RBL5 que expresaron cantidades semejantes de HBsAgayw y HBsAgadw2, (datos no mostrados). Las partículas recombinantes de HBsAg de los subtipos ayw, adw2 y adr se encuentran disponibles en la empresa Rhein Biotech GmbH (Düsseldorf, Alemania). Las partículas de HBsAg preparadas en la cepa hospedera de Hansenula polymorpha RB10 se purificaron tal como se describe en [3]. Los péptidos sintéticos ILSPFLPL (ayw) o IVSPFIPL (subtipo adw2) de S208-215 Kb-enlazantes, y los péptidos VWLSVIWM (ayw) o VWLSAIWM (adw2) de S190-197 Kb-enlazantes se obtuvieron de Jerini BioTools (Berlin, Alemania). Los péptidos se disolvieron en una solución de DMSO a una concentración de 10 mg/ml y se diluyeron con un medio de cultivo antes de uso.
Plásmidos e inmunización con ADN
8
Claims (1)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| DE10339927A DE10339927A1 (de) | 2003-08-29 | 2003-08-29 | Zusammensetzung zur Prophylaxe/Therapie von HBV-Infektionen und HBV-vermittelten Erkrankungen |
| DE10339927 | 2003-08-29 | ||
| PCT/EP2004/009590 WO2005023297A1 (de) | 2003-08-29 | 2004-08-27 | Zusammensetzung zur prophylaxe/therapie von hbv-infektionen und hbv-vermittelten erkrankungen |
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| EP (1) | EP1660125B1 (es) |
| JP (1) | JP4740133B2 (es) |
| KR (2) | KR101250029B1 (es) |
| CN (1) | CN1874787B (es) |
| AU (1) | AU2004269882B2 (es) |
| BR (1) | BRPI0414026A (es) |
| CA (1) | CA2535734A1 (es) |
| DE (1) | DE10339927A1 (es) |
| ES (1) | ES2541123T3 (es) |
| HK (1) | HK1100812A1 (es) |
| WO (1) | WO2005023297A1 (es) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP1764369A1 (de) | 2005-09-16 | 2007-03-21 | Rhein Biotech Gesellschaft für neue biotechnologische Prozesse und Produkte mbH | Vakzine enthaltend trunkiertes HBV core protein plus Saponin-basierendes Adjuvants |
| KR100836745B1 (ko) * | 2007-01-31 | 2008-06-10 | (주)두비엘 | Ｈｂｖ 백신 및 그의 제조 방법 |
| US9052304B2 (en) | 2009-03-13 | 2015-06-09 | Terrasep, Llc | Methods and apparatus for centrifugal liquid chromatography |
| US9393299B2 (en) * | 2009-08-07 | 2016-07-19 | Transgene S.A. | Composition for treating HBV infection |
| US10076570B2 (en) | 2009-08-07 | 2018-09-18 | Transgene S.A. | Composition for treating HBV infection |
| US9238679B2 (en) * | 2011-02-11 | 2016-01-19 | The Trustees Of The University Of Pennslyvania | Nucleic acid molecule encoding hepatitis B virus core protein and surface antigen protein and vaccine comprising the same |
| MA34956B1 (fr) | 2011-02-12 | 2014-03-01 | Globeimmune Inc | Therapeutique a base de levure pour infection chronique par l'hepatite b |
| EA029137B1 (ru) | 2011-04-21 | 2018-02-28 | Ионис Фармасьютикалз, Инк. | Модулирование экспрессии вируса гепатита в (hbv) |
| EP2629096A1 (en) * | 2012-02-20 | 2013-08-21 | Roche Diagniostics GmbH | HBV immunocomplexes for response prediction and therapy monitoring of chronic HBV patients |
| KR101646830B1 (ko) * | 2013-05-31 | 2016-08-08 | (주)셀트리온 | Ｂ형 간염 바이러스를 중화시킬 수 있는 결합 분자 |
| RU2733496C2 (ru) * | 2015-03-16 | 2020-10-02 | Гельмгольц Центрум Мюнхен - Дойчес Форшунгсцентрум Фюр Гезундхайт Унд Умвельт (Гмбх) | Триспецифические связывающие молекулы для лечения вирусной инфекции гепатита в и связанных состояний |
| CN113058033B (zh) * | 2019-12-16 | 2024-07-09 | 远大赛威信生命科学(南京)有限公司 | 一种用于预防和治疗乙型肝炎的药物组合物及其用途 |
| WO2023143445A1 (zh) * | 2022-01-25 | 2023-08-03 | 厦门大学 | 用于治疗hbv感染及相关疾病的表位肽及抗体 |
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| US5196194A (en) * | 1979-05-24 | 1993-03-23 | The Regents Of The University Of California | Vaccines containing Hepatitis B S-protein |
| EP0389983A3 (en) * | 1989-03-31 | 1991-01-16 | Abbott Laboratories | Monoclonal antibodies to pres2 and pres1 polypeptides of the hepatitis b viral envelope |
| PT97632A (pt) * | 1990-05-11 | 1992-03-31 | Scripps Clinic Res | Processo de obtencao de polipeptidos relacionados com a proteina do antigenio de superficie do virus da hepatite b e de vacinas que os contem |
| CA2041772A1 (en) * | 1990-05-11 | 1991-11-12 | Larry T. Mimms | Monoclonal antibodies to pres2 and pres1 polypeptide of the hepatitis b viral envelope |
| EP0491077A1 (en) * | 1990-12-19 | 1992-06-24 | Medeva Holdings B.V. | A composition used as a therapeutic agent against chronic viral hepatic diseases |
| IL101653A0 (en) * | 1991-04-29 | 1992-12-30 | Merck & Co Inc | Multiple hepatitis b virus surface proteins which form particles |
| EP0533263A3 (en) * | 1991-09-20 | 1994-06-08 | Merck & Co Inc | A multivalent hepatitis b virus vaccine |
| US6133244A (en) * | 1993-10-22 | 2000-10-17 | Institut Pasteur | Method for immunization against hepatitis B |
| ZA973367B (en) * | 1996-04-19 | 1997-11-18 | Innogenetics Nv | Method for typing and detecting HBV. |
| GB9608626D0 (en) * | 1996-04-25 | 1996-07-03 | Univ College Of London | Hepatitis b monoclonal antibodies |
| EP1234040A2 (en) * | 1999-12-03 | 2002-08-28 | Innogenetics N.V. | Hbv sequences |
| JP2001294599A (ja) * | 2000-04-12 | 2001-10-23 | Sekisui Chem Co Ltd | 組み換えｂ型肝炎ウィルス表面抗原 |
| RU2286172C2 (ru) * | 2000-08-17 | 2006-10-27 | Трипеп Аб | Вакцины, содержащие рибавирин, и способы их использования |
| RU2233672C1 (ru) * | 2003-03-31 | 2004-08-10 | Закрытое акционерное общество научно-производственная компания "Комбиотех" | Комбинированная вакцина для иммунопрофилактики вирусного гепатита в и д, столбняка и дифтерии |
| RU2233673C1 (ru) * | 2003-03-31 | 2004-08-10 | Закрытое акционерное общество научно-производственная компания "Комбиотех" | Комбинированная вакцина для иммунопрофилактики коклюша, дифтерии, столбняка и вирусного гепатита в и д |
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2003
- 2003-08-29 DE DE10339927A patent/DE10339927A1/de not_active Ceased
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2004
- 2004-08-27 BR BRPI0414026-5A patent/BRPI0414026A/pt not_active IP Right Cessation
- 2004-08-27 KR KR1020067004038A patent/KR101250029B1/ko not_active IP Right Cessation
- 2004-08-27 ES ES04764564.3T patent/ES2541123T3/es not_active Expired - Lifetime
- 2004-08-27 CN CN2004800317444A patent/CN1874787B/zh not_active Expired - Fee Related
- 2004-08-27 AU AU2004269882A patent/AU2004269882B2/en not_active Ceased
- 2004-08-27 CA CA002535734A patent/CA2535734A1/en not_active Abandoned
- 2004-08-27 JP JP2006524340A patent/JP4740133B2/ja not_active Expired - Fee Related
- 2004-08-27 WO PCT/EP2004/009590 patent/WO2005023297A1/de active Application Filing
- 2004-08-27 EP EP04764564.3A patent/EP1660125B1/de not_active Expired - Lifetime
- 2004-08-27 KR KR1020127003977A patent/KR20120026138A/ko not_active Application Discontinuation
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2006
- 2006-02-28 US US11/365,210 patent/US20060233832A1/en not_active Abandoned
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2007
- 2007-06-05 HK HK07105918.1A patent/HK1100812A1/xx not_active IP Right Cessation
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Also Published As
| Publication number | Publication date |
|---|---|
| EP1660125A1 (de) | 2006-05-31 |
| BRPI0414026A (pt) | 2006-10-24 |
| JP2007504112A (ja) | 2007-03-01 |
| US20060233832A1 (en) | 2006-10-19 |
| CN1874787B (zh) | 2012-09-19 |
| CN1874787A (zh) | 2006-12-06 |
| JP4740133B2 (ja) | 2011-08-03 |
| KR20070019632A (ko) | 2007-02-15 |
| AU2004269882B2 (en) | 2010-02-18 |
| DE10339927A1 (de) | 2005-03-24 |
| EP1660125B1 (de) | 2015-05-06 |
| KR101250029B1 (ko) | 2013-04-09 |
| KR20120026138A (ko) | 2012-03-16 |
| AU2004269882A1 (en) | 2005-03-17 |
| HK1100812A1 (en) | 2007-09-28 |
| US20110263822A1 (en) | 2011-10-27 |
| WO2005023297A1 (de) | 2005-03-17 |
| CA2535734A1 (en) | 2005-03-17 |
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