JP2008505656A - フラビウイルスワクチン - Google Patents
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Abstract
Description
本発明は、フラビウイルス科のウイルスに関する。フラビウイルス属は約70のメンバーを含み、この中の40種は人間の病気と関連する。フラビウイルスの大多数は、アボウイルスであり、ダニと蚊によって鳥類および哺乳動物(ヒトを含む)の宿主に感染する。デング熱ウイルス(1型〜4型)、黄熱病ウイルス、日本脳炎ウイルス、ダニ媒介性脳炎ウイルスおよび西ナイルウイルスは、人類において、かなりの罹患率および死亡率の原因物質である。いくつのフラビウイルス、例えば、羊において神経系疾患を引き起こす跳躍病ウイウス、馬において脳炎を引き起こす西ナイルウイルス、ならびに馬における脳炎および飼育豚における死産を引き起こす日本脳炎ウイルスは、重要な獣医学的病原体である。
Holstead,SB,「Immunological parameters of togavirus disease syndromes」,RW Schlesinger(編)The Togaviruses,Academic Press,Inc.,NY,1980年、p.107−173 Sabin,AB,「Dengue」,T RiversおよびF Horsfall(編),Viral and Rickettsial Infections of Man,JB Lippincott Co.,Philadelphia,1959,p.361−373 World Health Organization:1975.Technical Guides for Diagnosis,Treatment,Surveillance,Prevention and Control of Dengue Hemorrhagic Fever.World Health Organization.Geneva
本発明は、フラビウイルスワクチンを作製するための物質および方法に関する。このワクチンは、ウイルス様粒子(VLP)を含む。このVLPは、宿主細胞に感染することができ、その宿主細胞内で複製することができ、宿主免疫系によって認識されるウイルスタンパク質を産生することができるが、感染性ウイルス粒子内へはパッケージングされることができない。この目的のVLPは、レプリコンRNA産生およびフラビウイルスタンパク質の産生を確実にする全ての必要な遺伝しを有するレプリコンを含有する。従って、好ましいレプリンコは、全ての非構造タンパク質遺伝子であるpreMおよびE遺伝子を含有するレプリコンである。しかしながら、カプシド遺伝子は、カプシドタンパク質が作製されないか、または感染性ウイルス粒子を作製するためには使用され得ないかのいずれかであることを確実にするように、かつpreMおよびEタンパク質の高レベルの発現を確実にするように、操作されている。この目的のウイルス様粒子は、宿主細胞に感染することができ、次いで、多コピーのレプリコンがその細胞内で作製され、このレプリコンが発現してpreMおよびEタンパク質を産生する。このpreMおよびEタンパク質は、その細胞から放出されることもできるし、その細胞表面上で発現されることもでき、それによってこの目的のワクチンは、宿主の体液性応答および細胞性応答の両方を惹起する。
フラビウイルスは、RNA6%、タンパク質66%、炭水化物9%および脂質17%から構成される(Russell PK,Brandt WE,Dalrymple JM,Chemical and Antigenic Structure of Flaviviruses,Schlesinger RW編、The Togaviruses:Biology,Structure,Replication.New York:Academic;1980:503−529;およびTrent DW,Naeve CW,Biochemistry and Replication,Monath T編、St.Louis Encephalitis.Washington,DC:American Public Health Association;1980、p.159−199)。高電子密度ヌクレオカプシドは、C(カプシド)タンパク質およびゲノムRNAから構成される。エンベロープタンパク質E、および膜(M)タンパク質は、C末端疎水性アンカーによって脂質二重層に埋め込まれる。しかしながら、細胞内小胞で見られる未熟な粒子は、プロセシングされていないprMを含み、放出されるビリオンよりも感染性が低い(Morens DM:Antibody−dependent enhancement of infection and the pathogenesis of viral disease.Clin Infect Dis 1994,19:500−512)。
Claims (15)
- エンベロープタンパク質の少なくとも1つの免疫学的決定基を発現するレプリコンを含む、非複製フラビウイルス粒子。
- 前記フラビウイルスは、デング熱ウイルスである、請求項1に記載の粒子。
- 前記フラビウイルスは、西ナイルウイルスである、請求項1に記載の粒子。
- 前記フラビウイルスは、日本脳炎ウイルスである、請求項1に記載の粒子。
- 前記フラビウイルスウイルスは、黄熱病ウイルスである、請求項1に記載の粒子。
- 前記レプリコンは、カプシドタンパク質を発現しない、請求項1に記載の粒子。
- 前記レプリコンが、前膜または膜タンパク質の少なくとも1つの免疫学的決定基を発現する、請求項1に記載の粒子。
- 請求項1に記載の粒子と、薬学的に受容可能なキャリア、希釈剤または賦形剤を含む、薬学的組成物。
- 請求項1に記載の粒子を作製する方法であって、該方法は、以下の工程;
宿主細胞を、少なくとも1つのフラビウイルスの免疫学的決定基を発現するレプリコンで形質転換する工程、
次いで、該宿主細胞を、請求項1に記載のレプリコンに相補的な遺伝子を含むレプリコンで形質転換する工程、および
該宿主細胞によって産生される粒子を単離する工程、
を包含する、方法。 - 前記相補的なレプリコンは、シンドビスウイルスC、prMおよびEのオープンリーディングフレームを含む、請求項9に記載の方法。
- 請求項1に記載の粒子を作製する方法であって、該方法は、以下の工程;
宿主細胞を、少なくとも1つのフラビウイルスの免疫学的決定基を発現し、かつ感染性ウイルス粒子を作製するのに必須な遺伝子産物は発現しないレプリコンで形質転換する工程を包含し、
ここで、該宿主細胞は、感染性遺伝子粒子を作製するのに必須な該遺伝子産物を発現する、
方法。 - 前記宿主細胞はCタンパク質を発現する、請求項11に記載の方法。
- 前記Cタンパク質の発現は、前記宿主細胞が前記レプリコンで形質転換されたときに誘導される、請求項12に記載の方法。
- フラビウイルス構造タンパク質を発現する、形質転換細胞。
- preMおよびEタンパク質を発現し、かつCタンパク質を発現することができないか、または感染性ウイルス粒子のカプシドを含むことができないCタンパク質を発現するフラビウイルスレプリコンをさらに含む、請求項14に記載の形質転換細胞。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US58672204P | 2004-07-12 | 2004-07-12 | |
PCT/US2005/024428 WO2006017206A2 (en) | 2004-07-12 | 2005-07-11 | Flavivirus vaccine |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2008505656A true JP2008505656A (ja) | 2008-02-28 |
Family
ID=35839757
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007521526A Pending JP2008505656A (ja) | 2004-07-12 | 2005-07-11 | フラビウイルスワクチン |
Country Status (4)
Country | Link |
---|---|
US (2) | US10040824B2 (ja) |
JP (1) | JP2008505656A (ja) |
CN (2) | CN103088038B (ja) |
WO (1) | WO2006017206A2 (ja) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011516040A (ja) * | 2008-03-14 | 2011-05-26 | サノフィ パスツール バイオロジクス カンパニー | 複製欠損フラビウイルスワクチンおよびワクチンベクター |
US9017980B2 (en) | 2005-04-11 | 2015-04-28 | Crealta Pharmaceuticals Llc | Variant forms of urate oxidase and use thereof |
US9885024B2 (en) | 1998-08-06 | 2018-02-06 | Duke University | PEG-urate oxidase conjugates and use thereof |
US10139399B2 (en) | 2009-06-25 | 2018-11-27 | Horizon Pharma Rheumatology Llc | Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response by monitoring serum uric acid during PEGylated uricase therapy |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2673593A1 (en) * | 2005-12-23 | 2007-07-05 | Hygea Biopharma, Inc. | Immunologically enhanced recombinant vaccines |
EP1991709B1 (en) | 2006-02-27 | 2017-01-25 | The Board of Regents of The University of Texas System | Pseudoinfectious flavivirus and uses thereof |
BE1023557B1 (fr) | 2014-02-10 | 2017-05-03 | Univercells Sa | Systeme, appareil et procede pour la production de biomolecules |
KR102239090B1 (ko) * | 2014-06-05 | 2021-04-13 | 삼성전자 주식회사 | 위치 정보를 제공하기 위한 방법 및 장치 |
WO2017165317A2 (en) * | 2016-03-20 | 2017-09-28 | Samuel Bogoch | Therapies, vaccines, and predictive methods for flaviviruses |
CN113637697B (zh) * | 2021-07-13 | 2024-06-14 | 中山大学 | 一种denv-4全长感染性克隆及其构建方法 |
Citations (4)
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JP2002500003A (ja) * | 1997-11-28 | 2002-01-08 | ザ・クラウン・イン・ザ・ライト・オヴ・ザ・クイーンズランド・デパートメント・オヴ・ヘルス | フラビウイルスの発現および送達のシステム |
WO2002072803A2 (en) * | 2001-03-09 | 2002-09-19 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Subgenomic replicons of the flavivirus dengue |
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DK1625852T3 (da) * | 1997-02-28 | 2010-09-20 | Sanofi Pasteur Biologics Co | Kimæriske flavivirusvacciner |
FR2832270B1 (fr) | 2001-11-15 | 2006-07-28 | Centre Nat Rech Scient | Procede de reglage de l'ecartement de deux elements mecaniques d'une structure micromecanique sensiblement plane et resonateur electromecanique correspondant |
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EP1991709B1 (en) | 2006-02-27 | 2017-01-25 | The Board of Regents of The University of Texas System | Pseudoinfectious flavivirus and uses thereof |
-
2005
- 2005-07-11 WO PCT/US2005/024428 patent/WO2006017206A2/en active Application Filing
- 2005-07-11 CN CN201310014662.XA patent/CN103088038B/zh not_active Expired - Fee Related
- 2005-07-11 JP JP2007521526A patent/JP2008505656A/ja active Pending
- 2005-07-11 CN CN2005800304379A patent/CN101018860B/zh not_active Expired - Fee Related
-
2007
- 2007-01-11 US US11/622,233 patent/US10040824B2/en active Active
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2018
- 2018-08-06 US US16/056,314 patent/US20180340011A1/en not_active Abandoned
Patent Citations (4)
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JP2002500003A (ja) * | 1997-11-28 | 2002-01-08 | ザ・クラウン・イン・ザ・ライト・オヴ・ザ・クイーンズランド・デパートメント・オヴ・ヘルス | フラビウイルスの発現および送達のシステム |
US20040052818A1 (en) * | 2001-02-21 | 2004-03-18 | Heinz Franz Xaver | Attenuated live vaccine |
WO2002072803A2 (en) * | 2001-03-09 | 2002-09-19 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Subgenomic replicons of the flavivirus dengue |
WO2002081754A1 (en) * | 2001-04-04 | 2002-10-17 | The Governement Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services, Centers For Disease Control And Prevention | Nucleic acid vaccines for prevention of flavivirus infection |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9885024B2 (en) | 1998-08-06 | 2018-02-06 | Duke University | PEG-urate oxidase conjugates and use thereof |
US11345899B2 (en) | 2005-04-11 | 2022-05-31 | Horizon Therapeutics Usa, Inc. | Variant forms of urate oxidase and use thereof |
US9017980B2 (en) | 2005-04-11 | 2015-04-28 | Crealta Pharmaceuticals Llc | Variant forms of urate oxidase and use thereof |
US9670467B2 (en) | 2005-04-11 | 2017-06-06 | Horizon Pharma Rheumatology Llc | Variant forms of urate oxidase and use thereof |
US9926537B2 (en) | 2005-04-11 | 2018-03-27 | Horizon Pharma Rheumatology Llc | Variant forms of urate oxidase and use thereof |
US9926538B2 (en) | 2005-04-11 | 2018-03-27 | Horizon Pharma Rheumatology Llc | Variant forms of urate oxidase and use thereof |
US10160958B2 (en) | 2005-04-11 | 2018-12-25 | Horizon Pharma Rheumatology Llc | Variant forms of urate oxidase and use thereof |
US10731139B2 (en) | 2005-04-11 | 2020-08-04 | Horizon Pharma Rheumatology Llc | Variant forms of urate oxidase and use thereof |
US11781119B2 (en) | 2005-04-11 | 2023-10-10 | Horizon Therapeutics Usa, Inc. | Variant forms of urate oxidase and use thereof |
JP2011516040A (ja) * | 2008-03-14 | 2011-05-26 | サノフィ パスツール バイオロジクス カンパニー | 複製欠損フラビウイルスワクチンおよびワクチンベクター |
US10139399B2 (en) | 2009-06-25 | 2018-11-27 | Horizon Pharma Rheumatology Llc | Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response by monitoring serum uric acid during PEGylated uricase therapy |
US11598767B2 (en) | 2009-06-25 | 2023-03-07 | Horizon Therapeutics Usa, Inc. | Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response by monitoring serum uric acid during pegylated uricase therapy |
US11639927B2 (en) | 2009-06-25 | 2023-05-02 | Horizon Therapeutics Usa, Inc. | Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response by monitoring serum uric acid during PEGylated uricase therapy |
US10823727B2 (en) | 2009-06-25 | 2020-11-03 | Horizon Pharma Rheumatology Llc | Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response by monitoring serum uric acid during pegylated uricase therapy |
US11982670B2 (en) | 2009-06-25 | 2024-05-14 | Horizon Therapeutics Usa, Inc. | Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response by monitoring serum uric acid during pegylated uricase therapy |
Also Published As
Publication number | Publication date |
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WO2006017206A2 (en) | 2006-02-16 |
WO2006017206A3 (en) | 2007-02-01 |
CN101018860B (zh) | 2013-02-27 |
CN103088038A (zh) | 2013-05-08 |
CN101018860A (zh) | 2007-08-15 |
US20070249032A1 (en) | 2007-10-25 |
US20180340011A1 (en) | 2018-11-29 |
CN103088038B (zh) | 2015-06-24 |
US10040824B2 (en) | 2018-08-07 |
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