JP5654345B2 - 多量体マルチエピトープインフルエンザワクチン - Google Patents
多量体マルチエピトープインフルエンザワクチン Download PDFInfo
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- JP5654345B2 JP5654345B2 JP2010518815A JP2010518815A JP5654345B2 JP 5654345 B2 JP5654345 B2 JP 5654345B2 JP 2010518815 A JP2010518815 A JP 2010518815A JP 2010518815 A JP2010518815 A JP 2010518815A JP 5654345 B2 JP5654345 B2 JP 5654345B2
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| CN104203272A (zh) * | 2012-01-26 | 2014-12-10 | 长角牛疫苗和诊断有限责任公司 | 复合抗原序列及疫苗 |
| CN104395346A (zh) * | 2012-04-02 | 2015-03-04 | 弗利亚生物技术公司 | 重组木瓜花叶病毒外壳蛋白及其在流感疫苗中的应用 |
| CN103055311B (zh) * | 2012-12-28 | 2014-05-21 | 中山大学 | 一种传染性喉气管炎粘膜疫苗及其制备方法和应用 |
| US20140193484A1 (en) * | 2013-01-10 | 2014-07-10 | Sylvie Carine Bertholet Girardin | Influenza virus immunogenic compositions and uses thereof |
| CA2944768C (en) | 2014-04-03 | 2022-08-30 | Biondvax Pharmaceuticals Ltd. | Compositions of multimeric-multiepitope influenza polypeptides and their production |
| SG10202108573TA (en) * | 2016-02-03 | 2021-09-29 | Cg Discovery Inc | Compositions of influenza hemagglutinin with heterologous epitopes and/or altered maturation cleavage sites |
| JP2019064924A (ja) * | 2016-02-24 | 2019-04-25 | Ａｇｃ株式会社 | インフルエンザワクチン |
| EP3562498A4 (en) | 2016-12-28 | 2020-10-28 | Invvax, Inc. | INFLUENZA VACCINES |
| WO2019061297A1 (zh) * | 2017-09-29 | 2019-04-04 | 苏州工业园区唯可达生物科技有限公司 | 一种cd4辅助性t细胞表位融合肽及其疫苗 |
| CN111556896A (zh) * | 2017-12-21 | 2020-08-18 | 株式会社绿色生物医药 | 交叉免疫抗原疫苗及其制备方法 |
| EP3774841A1 (en) | 2018-08-27 | 2021-02-17 | Regeneron Pharmaceuticals, Inc. | Use of raman spectroscopy in downstream purification |
| EP3851120A4 (en) * | 2018-09-11 | 2022-04-27 | Shanghai Public Health Clinical Center | Immunogen for broad-spectrum influenza vaccine and application thereof |
| WO2020257317A1 (en) * | 2019-06-18 | 2020-12-24 | Citranvi Biosciences, Llc | Rationally engineered carrier proteins for vaccines |
| JP2023513720A (ja) * | 2020-02-14 | 2023-04-03 | ユニバーシティ オブ ワシントン | 感染症の治療又は発症を制限するためのポリペプチド、組成物、及びそれらの使用 |
| US11149286B1 (en) | 2020-08-17 | 2021-10-19 | Mayo Foundation For Medical Education And Research | Adenovirus vectors and methods for using adenovirus vectors |
| US20230364261A1 (en) * | 2020-09-21 | 2023-11-16 | Sri International | Targeted antigen delivery system and uses thereof |
Family Cites Families (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4767842A (en) * | 1973-05-07 | 1988-08-30 | The Ohio State University | Antigenic modification of polypeptides |
| IL61904A (en) * | 1981-01-13 | 1985-07-31 | Yeda Res & Dev | Synthetic vaccine against influenza virus infections comprising a synthetic peptide and process for producing same |
| US4436727A (en) * | 1982-05-26 | 1984-03-13 | Ribi Immunochem Research, Inc. | Refined detoxified endotoxin product |
| US4866034A (en) * | 1982-05-26 | 1989-09-12 | Ribi Immunochem Research Inc. | Refined detoxified endotoxin |
| US4643992A (en) * | 1982-11-09 | 1987-02-17 | Scripps Clinic And Research Foundation | Modulation of animal cellular responses with compositions containing 8-substituted guanine derivatives |
| US4539205A (en) * | 1982-11-09 | 1985-09-03 | Scripps Clinic And Research Foundation | Modulation of animal cellular responses with compositions containing 8-substituted guanine derivatives |
| US4987237A (en) * | 1983-08-26 | 1991-01-22 | Ribi Immunochem Research, Inc. | Derivatives of monophosphoryl lipid A |
| US5093318A (en) * | 1983-11-01 | 1992-03-03 | Scripps Clinic And Research Foundation | Immunostimulating guanosine derivatives and their pharmaceutical compositions |
| US5011828A (en) * | 1985-11-15 | 1991-04-30 | Michael Goodman | Immunostimulating guanine derivatives, compositions and methods |
| US5057540A (en) * | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
| US6130082A (en) * | 1988-05-05 | 2000-10-10 | American Cyanamid Company | Recombinant flagellin vaccines |
| JPH0832638B2 (ja) | 1989-05-25 | 1996-03-29 | カイロン コーポレイション | サブミクロン油滴乳剤を含んで成るアジュバント製剤 |
| US5709879A (en) * | 1990-06-29 | 1998-01-20 | Chiron Corporation | Vaccine compositions containing liposomes |
| US5837268A (en) * | 1991-10-16 | 1998-11-17 | University Of Saskatchewan | GnRH-leukotoxin chimeras |
| GB9201139D0 (en) | 1992-01-20 | 1992-03-11 | Connaught Lab | Synthetic peptides for a rubella vaccine |
| IL101639A0 (en) | 1992-04-17 | 1992-12-30 | Yeda Res & Dev | Recombinant influenza vaccines |
| PT761231E (pt) * | 1992-06-25 | 2000-06-30 | Smithkline Beecham Biolog | Composicao de vacina contendo adjuvantes |
| EP0625043B1 (en) * | 1992-09-16 | 2002-03-20 | The University Of Tennessee Research Corporation | Recombinant multivalent m protein vaccine |
| US5683695A (en) * | 1993-02-10 | 1997-11-04 | United Biomedical, Inc. | Production of recombinant proteins containing multiple antigenic determinants linked by flexible hinge domains |
| SK117395A3 (en) * | 1993-03-23 | 1996-11-06 | Smithkline Beecham Biolog | Vaccine composition and manufacturing process thereof |
| GB9326253D0 (en) | 1993-12-23 | 1994-02-23 | Smithkline Beecham Biolog | Vaccines |
| ES2366201T3 (es) | 1994-07-15 | 2011-10-18 | University Of Iowa Research Foundation | Oligonucleótidos inmunmoduladores. |
| UA56132C2 (uk) | 1995-04-25 | 2003-05-15 | Смітклайн Бічем Байолоджікалс С.А. | Композиція вакцини (варіанти), спосіб стабілізації qs21 відносно гідролізу (варіанти), спосіб приготування композиції вакцини |
| CO4600681A1 (es) | 1996-02-24 | 1998-05-08 | Boehringer Ingelheim Pharma | Composicion farmaceutica para la modulacion inmunitaria |
| US6113918A (en) * | 1997-05-08 | 2000-09-05 | Ribi Immunochem Research, Inc. | Aminoalkyl glucosamine phosphate compounds and their use as adjuvants and immunoeffectors |
| US6303347B1 (en) * | 1997-05-08 | 2001-10-16 | Corixa Corporation | Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectors |
| US6355257B1 (en) * | 1997-05-08 | 2002-03-12 | Corixa Corporation | Aminoalkyl glucosamine phosphate compounds and their use as adjuvants and immunoeffectors |
| US7063967B2 (en) * | 1997-05-08 | 2006-06-20 | Corixa Corporation | Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectors |
| AU732856B2 (en) * | 1997-05-20 | 2001-05-03 | Galenica Pharmaceuticals, Inc. | Triterpene saponin analogs having adjuvant and immunostimulatory activity |
| US6080725A (en) * | 1997-05-20 | 2000-06-27 | Galenica Pharmaceuticals, Inc. | Immunostimulating and vaccine compositions employing saponin analog adjuvants and uses thereof |
| CA2297786C (en) | 1997-08-05 | 2011-06-14 | Vlaams Interuniversitair Instituut Voor Biotechnologie | New immunoprotective influenza antigen and its use in vaccination |
| GB9718901D0 (en) | 1997-09-05 | 1997-11-12 | Smithkline Beecham Biolog | Vaccine |
| JP4426091B2 (ja) * | 1997-09-05 | 2010-03-03 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | サポニンを含有する水中油型エマルション |
| AU6253898A (en) * | 1997-12-16 | 1999-07-05 | Chiron Corporation | Use of microparticles combined with submicron oil-in-water emulsions |
| KR20010042573A (ko) | 1998-04-09 | 2001-05-25 | 장 스테판느 | 애쥬번트 조성물 |
| GB9807805D0 (en) | 1998-04-09 | 1998-06-10 | Smithkline Beecham Biolog | Vaccine |
| US6630161B1 (en) | 1998-05-07 | 2003-10-07 | Ribi Immunochem Research, Inc. | Adjuvant composition and methods for its use |
| CA2337754C (en) * | 1998-08-21 | 2011-05-24 | Altaf A. Lal | Recombinant multivalent malarial vaccine against plasmodium falciparum |
| IL127331A0 (en) * | 1998-11-30 | 1999-09-22 | Yeda Res & Dev | Peptide-based vaccine for influenza |
| CA2377525A1 (en) | 1999-07-19 | 2001-03-29 | Epimmune, Inc. | Inducing cellular immune responses to hepatitis c virus using peptide and nucleic acid compositions |
| WO2001024810A1 (en) | 1999-10-05 | 2001-04-12 | Epimmune Inc. | Inducing cellular immune responses to human immunodeficiency virus-1 using peptide and nucleic acid compositions |
| US6843781B2 (en) * | 1999-10-14 | 2005-01-18 | Becton, Dickinson And Company | Intradermal needle |
| DK1294892T3 (da) | 2000-06-23 | 2008-01-28 | Wyeth Corp | Aggregering af vildtype- og kimære influenzaviruslignende partikler (VLP'er) |
| AU2003279750A1 (en) * | 2002-06-28 | 2004-01-19 | Nastech Pharmaceutical Company Inc. | Compositions and methods for modulating physiology of epithelial junctional adhesion molecules for enhanced mucosal delivery of therapeutic compounds |
| WO2004080403A2 (en) | 2003-03-07 | 2004-09-23 | Merck & Co. Inc. | Influenza virus vaccine |
| US7108679B2 (en) * | 2004-03-11 | 2006-09-19 | Becton, Dickinson And Company | Intradermal syringe and needle assembly |
| CA2589553C (en) * | 2004-12-16 | 2014-02-18 | Wake Forest University Health Sciences | Use of flagellin in the immunotherapy of yersinia pestis |
| WO2006069262A2 (en) | 2004-12-21 | 2006-06-29 | Vaxinnate Corporation | Compositions of influenza viral proteins and methods of use thereof |
| MY157941A (en) | 2005-01-19 | 2016-08-15 | Vaxinnate Corp | Compositions of pathogen-associated molecular patterns and methods of use |
| US20090104216A1 (en) * | 2005-06-01 | 2009-04-23 | Variation Biotechnologies, Inc. | Peptide-Based Influenza Vaccine Formulation |
| US7260958B2 (en) * | 2005-09-14 | 2007-08-28 | National Taipei University Technology | Electrohydrodynamic condenser device |
| EP1945253A2 (en) * | 2005-11-04 | 2008-07-23 | Novartis Vaccines and Diagnostics S.r.l. | Adminstration routes for priming/boosting with influenza vaccines |
| ES2385842T3 (es) * | 2005-12-06 | 2012-08-01 | Yeda Research And Development Co., Ltd. | Vacuna mejorada contra la gripe |
| GB0613977D0 (en) | 2006-02-07 | 2006-08-23 | Peptcell Ltd | Peptide sequences and compositions |
| WO2008039267A2 (en) * | 2006-07-21 | 2008-04-03 | Pharmexa Inc. | Inducing cellular immune responses to influenza virus using peptide and nucleic acid compositions |
| PE20090146A1 (es) * | 2007-04-20 | 2009-03-23 | Glaxosmithkline Biolog Sa | Composicion inmunogenica contra el virus influenza |
| KR20100075843A (ko) | 2007-08-21 | 2010-07-05 | 다이나박스 테크놀로지 코퍼레이션 | 인플루엔자 단백질 조성물 및 그 제조 및 사용 방법 |
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| CA2695399C (en) | 2017-10-17 |
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| KR101580660B1 (ko) | 2015-12-28 |
| KR20100045473A (ko) | 2010-05-03 |
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| PT2173376E (pt) | 2015-07-30 |
| EP2173376B1 (en) | 2015-03-25 |
| CA2695399A1 (en) | 2009-02-05 |
| AU2008281384B2 (en) | 2012-02-16 |
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| CN101795709B (zh) | 2013-07-17 |
| EA017887B1 (ru) | 2013-03-29 |
| EP2173376A2 (en) | 2010-04-14 |
| BRPI0815008B1 (pt) | 2019-11-19 |
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