JP5967585B2 - ワクチンとして使用される無毒化大腸菌易熱性エンテロトキシン(lt)との多糖結合 - Google Patents
ワクチンとして使用される無毒化大腸菌易熱性エンテロトキシン(lt)との多糖結合 Download PDFInfo
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- JP5967585B2 JP5967585B2 JP2013508580A JP2013508580A JP5967585B2 JP 5967585 B2 JP5967585 B2 JP 5967585B2 JP 2013508580 A JP2013508580 A JP 2013508580A JP 2013508580 A JP2013508580 A JP 2013508580A JP 5967585 B2 JP5967585 B2 JP 5967585B2
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- AZXBUJAUZGTXCC-KYHHOPLUSA-N CC[C@@H](C(C(CNC)OCC)C=N)Cl Chemical compound CC[C@@H](C(C(CNC)OCC)C=N)Cl AZXBUJAUZGTXCC-KYHHOPLUSA-N 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
- A61K39/092—Streptococcus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/102—Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/646—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6037—Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
Description
CFU:コロニー形成単位
ELISA:酵素結合免疫吸着測定法
Hib:インフルエンザ菌b型
IEF:等電点電気泳動
LT:易熱性エンテロトキシン
MALLS:多角度レーザー光散乱
OD:光学密度
PNPS:肺炎球菌多糖
PRP:ポリリボシルリビトールリン酸
PS:多糖
SDS−PAGE:ドデシル硫酸ナトリウムポリアクリルアミドゲル電気泳動法
SEC_HPLC:サイズ排除高圧液体クロマトグラフィー
RI:反射率(reflective index)
[0037]さまざまな可能性のある結合プロセスが、図面の図3に図示されている。本発明に従って選択された還元アミノ化プロセスの一般化されたフローチャートは、Glyconjugate J. 1989年、6:489頁に見出され、図面の図4として再現されている。
[0053]ニュージーランドシロウサギを、意図されたヒト用量の多糖、LTS61Kと混合した多糖、又は多糖−LTS61K結合体を用いて、2週間間隔で3回、筋肉内免疫感作して結合体ワクチンの効力を評価した。全てのワクチン調製物は、AlPO4又は他の関連アジュバントを含有しなかった。全てのワクチンの免疫応答は、抗多糖抗原特異的IgG力価を検出するためのELISA、及び抗体の機能的活性を検出するための血清殺菌アッセイにより決定した。試験結果は、結合に成功した多糖−LTS61Kワクチンのみが、多糖単独又はLTS61Kと混合された多糖のみよりも、血清中で高い多糖特異的IgG抗体力価及び大きい殺菌活性を誘導できることを示した。動物免疫原性試験は、LTS61Kタンパク質を含む無毒化大腸菌易熱性エンテロトキシンホロ毒素が、多糖抗原の特異的免疫応答を著しく刺激するのに多糖の担体タンパク質として有用であることを示唆している。
[0068]試験結果を、図面の図20〜23及び表3〜5を参照して以下に記載する。
Claims (10)
- ワクチンとして有用な多糖及び無毒化大腸菌易熱性エンテロトキシン(LT)の共有結合体であって、
可溶型であり、
前記LTが、野生型LTAのアミノ酸配列の61位に対応する位置にリシン置換を有するLTS61Kホロ毒素であり、3次構造を維持している、共有結合体。 - 感染性細菌の影響に対して防御又は免疫感作するための、請求項1に記載の共有結合体。
- 感染性細菌がインフルエンザ菌又は肺炎連鎖球菌である、請求項2に記載の共有結合体。
- 多糖がポリリボシルリビトールリン酸である、請求項1〜3のいずれか一項に記載の共有結合体。
- 精製された請求項1〜4のいずれか一項に記載の共有結合体を含む、哺乳動物に投与するためのワクチン。
- 感染性細菌の影響から哺乳動物を防御又は免疫感作するための医薬の製造における精製された請求項1〜4のいずれか一項に記載の共有結合体の使用。
- (a)多糖を過ヨウ素酸塩によって酸化する工程と、
(b)得られた多糖を還元アミノ化によってLTに結合させる工程と、
(c)得られた共有結合体を単離する工程と、
を含む、請求項1〜4のいずれか一項に記載の共有結合体を調製する方法。 - 前記多糖がポリリボシルリビトールリン酸であり、ポリリボシルリビトールリン酸:LTのモル比の範囲が3:1〜60:1の間である、請求項7に記載の方法。
- 旅行者下痢の影響から哺乳動物を防御又は免疫感作するための医薬の製造における精製された請求項1〜4のいずれか一項に記載の共有結合体の使用。
- 腸管毒素原性大腸菌由来の下痢の影響から哺乳動物を防御又は免疫感作するための医薬の製造における精製された請求項1〜4のいずれか一項に記載の共有結合体の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US33065010P | 2010-05-03 | 2010-05-03 | |
US61/330,650 | 2010-05-03 | ||
PCT/IB2011/001429 WO2012023008A2 (en) | 2010-05-03 | 2011-04-29 | Polysaccharide conjugation with detoxified e. coli heat labile enterotoxin (lt) used as vaccine |
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JP2014246147A Division JP2015071630A (ja) | 2010-05-03 | 2014-12-04 | ワクチンとして使用される無毒化大腸菌易熱性エンテロトキシン(lt)との多糖結合 |
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JP2013525474A JP2013525474A (ja) | 2013-06-20 |
JP5967585B2 true JP5967585B2 (ja) | 2016-08-10 |
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JP2013508580A Active JP5967585B2 (ja) | 2010-05-03 | 2011-04-29 | ワクチンとして使用される無毒化大腸菌易熱性エンテロトキシン(lt)との多糖結合 |
JP2014246147A Ceased JP2015071630A (ja) | 2010-05-03 | 2014-12-04 | ワクチンとして使用される無毒化大腸菌易熱性エンテロトキシン(lt)との多糖結合 |
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US (1) | US10624962B2 (ja) |
EP (1) | EP2566508B1 (ja) |
JP (2) | JP5967585B2 (ja) |
CN (2) | CN107261129A (ja) |
ES (1) | ES2550853T3 (ja) |
TW (2) | TWI451874B (ja) |
WO (1) | WO2012023008A2 (ja) |
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CN113616783A (zh) * | 2020-05-08 | 2021-11-09 | 昱厚生技股份有限公司 | 使用免疫调节剂和包含所述免疫调节剂的疫苗组合物预防或治疗冠状病毒感染的方法 |
CN113388008B (zh) * | 2021-06-25 | 2023-04-28 | 太原师范学院 | 一种细胞内质网靶向的自释放型蛋白运输载体lca2及其应用 |
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JPS5920226A (ja) * | 1982-07-26 | 1984-02-01 | Kitasato Inst:The | 動物用ワクチンおよびその製造法 |
US4808700A (en) * | 1984-07-09 | 1989-02-28 | Praxis Biologics, Inc. | Immunogenic conjugates of non-toxic E. coli LT-B enterotoxin subunit and capsular polymers |
CN1191357C (zh) * | 1998-12-22 | 2005-03-02 | 博伊斯·汤普生植物研究所 | 口服的免疫原性细菌肠毒素在转基因植物中的表达 |
US20050175631A1 (en) | 2002-01-14 | 2005-08-11 | Michael Vajdy | Hiv vaccine and method of use |
MXPA04011249A (es) * | 2002-05-14 | 2005-06-06 | Chiron Srl | Vacunas mucosales con adyuvante de quitosano y antigenos meningococicos. |
US20050002957A1 (en) * | 2003-05-07 | 2005-01-06 | Ryall Robert P. | Multivalent meningococcal derivatized polysaccharide-protein conjugates and vaccine |
GB0408978D0 (en) | 2004-04-22 | 2004-05-26 | Chiron Srl | Meningococcal fermentation for preparing conjugate vaccines |
US20070065462A1 (en) | 2005-09-21 | 2007-03-22 | Ryall Robert P | Multivalent meningococcal derivatized polysaccharide-protein conjugates and vaccine |
MX2009001412A (es) * | 2006-08-07 | 2009-04-24 | Harvard College | Vacunas de matriz de proteinas y metodos de hacer y administrar tales vacunas. |
TWI304838B (en) | 2006-10-27 | 2009-01-01 | Dev Center Biotechnology | Nucleotide acid sequence and amino acid sequence of e. coli heat-labile enterotoxin, and recombinant protein |
US8110197B2 (en) * | 2006-10-27 | 2012-02-07 | Development Center For Biotechnology | Mutated E. coli heat-labile enterotoxin |
BRPI0721746B1 (pt) * | 2007-07-18 | 2021-08-31 | Development Center For Biotechnology | Polipeptídeo isolado, vacina, ácido nucléico isolado, vetor e células transformadas de bactérias e fungos |
JP2011524375A (ja) | 2008-06-16 | 2011-09-01 | アカデミア シニカ | GloboHおよびSSEA3に特異的な免疫反応を誘起する組成物および癌治療におけるその使用 |
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2011
- 2011-04-29 CN CN201710238821.2A patent/CN107261129A/zh active Pending
- 2011-04-29 EP EP11817824.3A patent/EP2566508B1/en active Active
- 2011-04-29 ES ES11817824.3T patent/ES2550853T3/es active Active
- 2011-04-29 WO PCT/IB2011/001429 patent/WO2012023008A2/en active Application Filing
- 2011-04-29 JP JP2013508580A patent/JP5967585B2/ja active Active
- 2011-04-29 TW TW100115255A patent/TWI451874B/zh active
- 2011-04-29 CN CN2011800215281A patent/CN102858370A/zh active Pending
- 2011-04-29 TW TW102136855A patent/TW201406389A/zh unknown
- 2011-04-29 US US13/097,218 patent/US10624962B2/en active Active
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Publication number | Publication date |
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EP2566508A2 (en) | 2013-03-13 |
JP2015071630A (ja) | 2015-04-16 |
ES2550853T3 (es) | 2015-11-12 |
WO2012023008A3 (en) | 2012-05-24 |
JP2013525474A (ja) | 2013-06-20 |
CN102858370A (zh) | 2013-01-02 |
WO2012023008A2 (en) | 2012-02-23 |
US20110274717A1 (en) | 2011-11-10 |
US10624962B2 (en) | 2020-04-21 |
TW201138814A (en) | 2011-11-16 |
CN107261129A (zh) | 2017-10-20 |
TW201406389A (zh) | 2014-02-16 |
EP2566508B1 (en) | 2015-07-22 |
TWI451874B (zh) | 2014-09-11 |
EP2566508A4 (en) | 2013-10-09 |
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