JP5642080B2 - ワクチン製剤およびその使用 - Google Patents
ワクチン製剤およびその使用 Download PDFInfo
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- JP5642080B2 JP5642080B2 JP2011536514A JP2011536514A JP5642080B2 JP 5642080 B2 JP5642080 B2 JP 5642080B2 JP 2011536514 A JP2011536514 A JP 2011536514A JP 2011536514 A JP2011536514 A JP 2011536514A JP 5642080 B2 JP5642080 B2 JP 5642080B2
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Description
(a)改変されたワクシニアアンカラ(modified vaccinia Ankara)(MVA)ウイルス、またはその改変体もしくは誘導体;
および
(b)マンニトール
を含み、
ここで、(b)はその組成物の唯一の安定化剤である。
本発明の上記組成物は、安定である。
本発明はまた、以下の項目を提供する。
(項目1)
液体組成物または液体凍結組成物であって、該組成物は、
(a)改変されたワクシニアアンカラ(MVA)ウイルス、またはその改変体もしくは誘導体;
および
(b)マンニトール
を含み、(b)は該組成物の唯一の安定化剤である組成物。
(項目2)
マンニトールが、10℃と0℃との間の保存温度で安定化効果を提供する、項目1に記載の組成物。
(項目3)
上記組成物がワクチンであるか、または哺乳動物、好ましくは、ヒトにおける遺伝子療法、ウイルス療法、免疫療法、もしくはがん療法での使用のためである、項目1に記載の組成物。
(項目4)
上記組成物が生ワクチンである、項目3に記載の組成物。
(項目5)
上記ウイルスが、アデノウイルス、単純ヘルペス、水痘・帯状疱疹、サイトメガロウイルス、エプスタイン−バーウイルス、B型肝炎ウイルス、インフルエンザウイルス、ヒト乳頭腫ウイルス、パラインフルエンザウイルス、麻疹ウイルス、RSウイルス、ポリオウイルス、コクサッキーウイルス、ライノウイルス、A型肝炎ウイルス、ワクシニア、大痘瘡、小痘瘡、ロタウイルス、ヒトTリンパ球向性ウイルス−1、ヒト免疫不全ウイルス(HIV)、狂犬病ウイルス、風疹ウイルス、黄熱病ウイルス、アルボウイルス、Afipia spp、Brucella spp、Burkholderia pseudomallei、Chlamydia、Coxiella burnetii、Francisella tularensis、Legionella pneumophila、Listeria monocytogenes、Mycobacterium avium、Mycobacterium leprae、Mycobacterium tuberculosis、Neisseria gonorrhoeae、Rickettsiae、Salmonella typhi、Shigella dysenteriae、Yersinia pestis、Plasmodium spp、Theileria parva、Toxoplasma gondii、Cryptosporidium parvum、Leishmania、Trypanosoma cruziおよびCryptococcus neoformansからなる群より選択される微生物により引き起こされる、疾患または状態に対するワクチン接種のためである、項目4に記載の組成物。
(項目6)
上記組成物が実質的に水性である、項目1に記載の組成物。
(項目7)
0.01%と40%(w/v)との間のマンニトールを含む、項目1に記載の組成物。
(項目8)
0.1%と10%(w/v)との間のマンニトールを含む、項目7に記載の組成物。
(項目9)
約5%(w/v)のマンニトールを含む、項目8に記載の組成物。
(項目10)
改変されたワクシニアウイルス(MVA)、またはその改変体もしくは誘導体を含む、液体組成物または液体凍結組成物を安定化する方法であって、該方法は、十分な量のマンニトールを添加する工程を包含し、マンニトールは該組成物の唯一の安定化剤である方法。
(項目11)
上記組成物が、項目3または4のいずれか1項に定義されるとおりの目的のためである、項目10に記載の方法。
(項目12)
上記組成物の上記ウイルスが、項目5に定義されるとおりのものである、項目10または11のいずれか1項に記載の方法。
(項目13)
上記組成物が、項目6から9のいずれか1項に定義されるとおりのものである、項目10から12のいずれか1項に記載の方法。
(項目14)
改変されたワクシニアウイルス(MVA)、またはその改変体もしくは誘導体を含む、液体組成物または液体凍結組成物を安定化するためのマンニトールの使用であって、マンニトールが、該組成物の唯一の安定化剤である使用。
(項目15)
上記組成物が、項目3または4のいずれか1項に定義されるとおりの目的のためである、項目14に記載の使用。
(項目16)
上記組成物の上記ウイルスが、項目5に定義されるとおりのものである、項目14から15に記載の使用。
(項目17)
上記組成物が、項目6から9のいずれか1項に定義されるとおりのものである、項目14から16に記載の使用。
Xi=有効な個々の結果、サンプルのウイルスタイター[TCID50/ml]
n=個々の決定の数
凍結された食物の長期保存に使用される、従来のフリーザーまたは従来の低温室は、一般に生ワクチンの保存にも使用される。それらは、≦−15℃で作動するように設計されるが、頻繁に−18℃と−26℃との間の温度に達する。
本研究は、試験物として組換えMVAおよびMVAを使って行った。その組換えMVAは、遺伝子を基にした、抗がん性免疫治療用物質である。改変されたワクシニアアンカラ(Modified Vaccinia Ankara)(MVA)痘瘡(Smallpox)ワクチンは、痘瘡(smallpox)の予防および制御のための、弱毒化生ワクチンである。本研究の目的は、従来の冷蔵条件下で保存された液体製剤の安定性を試験することであった。
製剤
MVAの大規模な生産を、米国特許第5,391,491号に記載された方法の無血清の改変で達成した。製剤を、1×109TCID50/mlの標的タイターまで、TBSで希釈によるバッチMVAの希釈によって行った。
製剤を:
(i)−23℃±2℃;
(ii)<−60℃
で保存した。
マイクロタイタープレートに、5×105±20%細胞/mlの濃度で、100μlのCEC懸濁物を播種した。そのプレートをCO2インキュベーター内において36±2℃で一晩中インキュベートした。
MVA組成物は、トリス緩衝化生理食塩水(TBS;Tris−Buffered Saline)の中で−60℃より低い温度で39ヶ月間安定であることが見出された(図1を参照のこと)。通常の凍結条件下(すなわち、約−20℃)で保存された液体凍結製剤(liquid frozen formulation)もまた、安定であるという一般的な考えがあった。したがって、同じMVA TBS製剤が、通常の凍結温度で安定であると予想されていた。
液体MVA TBS製剤は、−22℃〜−23.4℃で不安定であることが見出された。この不安定性の原因は、この製剤についてのこの温度範囲に起こる水相の再結晶であり得る。その製剤は、5%(w/v)マンニトールの添加により、この温度範囲で安定化された。したがって、液体MVA TBS−マンニトール製剤は、代表的な保存温度の−23℃±2℃で安定である。
本液体製剤研究の目的は、トリス緩衝化生理食塩水(TBS)ワクチン製剤へのマンニトールの添加が、冷蔵(非凍結)保存の間にこの製剤の安定性に影響を与えるかどうかを決定することであった。
製剤
MVAの大規模な生産を、米国特許第5,391,491号に記載された方法の無血清の改変で達成した。製剤を、1×109TCID50/mlの標的タイターまで、TBSで希釈によるバッチMVAの希釈によって行った。5%の終濃度になるようにマンニトールを添加した。
(i)5℃±3℃
TCID50の決定
(上の)実施例Aのように。
保存の安定性
MVA TBS組成物は、2℃〜8℃で12ヶ月〜36ヶ月の期間にわたって保存される場合、不安定であることが見出された(図3を参照のこと)。しかしながら、5w/v%のマンニトールを含む3つのMVA TBS組成物は、18ヶ月の試験期間にわたって安定であることが見出された(図4を参照のこと)。
液体TBSワクチン製剤は、冷蔵温度(+2℃〜+8℃)で不安定であったが、5%マンニトールの添加が安定化効果を与えたことを、上記データは示唆する。
Claims (18)
- 液体組成物または液体凍結組成物であって、該組成物は、
(a)改変されたワクシニアアンカラ(MVA)ウイルス、またはその改変体もしくは誘導体;
および
(b)マンニトール
を含み、(b)は該組成物の唯一の安定化剤であり、該組成物には実質的に非ウイルスタンパク質がない、組成物。 - マンニトールが、10℃と0℃との間の保存温度で安定化効果を提供する、請求項1に記載の組成物。
- 前記組成物がワクチンであるか、または哺乳動物における遺伝子療法、ウイルス療法、免疫療法、もしくはがん療法での使用のためである、請求項1に記載の組成物。
- 前記哺乳動物がヒトである、請求項3に記載の組成物。
- 前記組成物が生ワクチンである、請求項3または4に記載の組成物。
- 前記ウイルスが、アデノウイルス、単純ヘルペス、水痘・帯状疱疹、サイトメガロウイルス、エプスタイン−バーウイルス、B型肝炎ウイルス、インフルエンザウイルス、ヒト乳頭腫ウイルス、パラインフルエンザウイルス、麻疹ウイルス、RSウイルス、ポリオウイルス、コクサッキーウイルス、ライノウイルス、A型肝炎ウイルス、ワクシニア、大痘瘡、小痘瘡、ロタウイルス、ヒトTリンパ球向性ウイルス−1、ヒト免疫不全ウイルス(HIV)、狂犬病ウイルス、風疹ウイルス、黄熱病ウイルス、アルボウイルス、Afipia spp、Brucella spp、Burkholderia pseudomallei、Chlamydia、Coxiella burnetii、Francisella tularensis、Legionella pneumophila、Listeria monocytogenes、Mycobacterium avium、Mycobacterium leprae、Mycobacterium tuberculosis、Neisseria gonorrhoeae、Rickettsiae、Salmonella typhi、Shigella dysenteriae、Yersinia pestis、Plasmodium spp、Theileria parva、Toxoplasma gondii、Cryptosporidium parvum、Leishmania、Trypanosoma cruziおよびCryptococcus neoformansからなる群より選択される微生物により引き起こされる、疾患または状態に対するワクチン接種のためである、請求項5に記載の組成物。
- 前記組成物が実質的に水性である、請求項1に記載の組成物。
- 0.01%と40%(w/v)との間のマンニトールを含む、請求項1に記載の組成物。
- 0.1%と10%(w/v)との間のマンニトールを含む、請求項8に記載の組成物。
- 約5%(w/v)のマンニトールを含む、請求項9に記載の組成物。
- 改変されたワクシニアウイルス(MVA)、またはその改変体もしくは誘導体を含む、液体組成物または液体凍結組成物を安定化する方法であって、該方法は、十分な量のマンニトールを添加する工程を包含し、マンニトールは該組成物の唯一の安定化剤であり、該組成物には実質的に非ウイルスタンパク質がない、方法。
- 前記組成物が、請求項3から5のいずれか1項に定義されるとおりの目的のためである、請求項11に記載の方法。
- 前記組成物の前記ウイルスが、請求項6に定義されるとおりのものである、請求項11または12のいずれか1項に記載の方法。
- 前記組成物が、請求項7から10のいずれか1項に定義されるとおりのものである、請求項11から13のいずれか1項に記載の方法。
- 改変されたワクシニアウイルス(MVA)、またはその改変体もしくは誘導体を含む、液体組成物または液体凍結組成物を安定化するためのマンニトールの使用であって、マンニトールが、該組成物の唯一の安定化剤であり、該組成物には実質的に非ウイルスタンパク質がない、使用。
- 前記組成物が、請求項3から5のいずれか1項に定義されるとおりの目的のためである、請求項15に記載の使用。
- 前記組成物の前記ウイルスが、請求項6に定義されるとおりのものである、請求項15から16に記載の使用。
- 前記組成物が、請求項7から10のいずれか1項に定義されるとおりのものである、請求項15から17に記載の使用。
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US7998488B2 (en) * | 2008-11-14 | 2011-08-16 | Baxter International Inc. | Vaccine formulations and uses thereof |
TWI527598B (zh) * | 2009-05-18 | 2016-04-01 | 英特威特國際股份有限公司 | 將致免疫組成物維持可供投與動物的方法 |
AU2012212463B2 (en) | 2011-01-31 | 2016-07-07 | Nanotherapeutics, Inc. | Recombinant viral vectors and methods for inducing a heterosubtypic immune response to influenza A viruses |
US8420617B2 (en) | 2011-03-11 | 2013-04-16 | Biocell Laboratories | Multiantivirus compound, composition and method for treatment of virus diseases |
US9314519B2 (en) | 2012-08-21 | 2016-04-19 | Intervet Inc. | Liquid stable virus vaccines |
US9480739B2 (en) | 2013-03-15 | 2016-11-01 | Intervet Inc. | Bovine virus vaccines that are liquid stable |
US9393298B2 (en) | 2013-03-15 | 2016-07-19 | Intervet Inc. | Liquid stable bovine virus vaccines |
AR097762A1 (es) | 2013-09-27 | 2016-04-13 | Intervet Int Bv | Formulaciones secas de vacunas que son estables a temperatura ambiente |
AR099470A1 (es) | 2014-02-17 | 2016-07-27 | Intervet Int Bv | Vacunas de virus de aves de corral líquidas |
TWI670085B (zh) | 2014-02-19 | 2019-09-01 | 荷蘭商英特威國際公司 | 液體穩定之豬病毒疫苗 |
AU2015357225B2 (en) * | 2014-12-01 | 2020-04-09 | Transgene Sa | Stable liquid vaccinia virus formulations |
CN109072582B (zh) | 2016-04-19 | 2022-02-08 | 沃尔沃建筑设备公司 | 用于材料的倾倒的控制单元 |
JP7051132B2 (ja) | 2016-09-16 | 2022-04-11 | ロイコケア・アクチェンゲゼルシャフト | ワクチン接種または遺伝子治療のための効率的なウイルスベクターベースの組成物を得るための新規方法 |
US20210187100A1 (en) | 2018-09-06 | 2021-06-24 | Bavarian Nordic A/S | Storage Improved Poxvirus Compositions |
BR112022017438A2 (pt) | 2020-03-12 | 2022-10-18 | Bavarian Nordic As | Composições que melhoram a estabilidade do poxvírus |
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US20100124557A1 (en) | 2010-05-20 |
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CA2747918A1 (en) | 2010-05-20 |
US8795683B2 (en) | 2014-08-05 |
AU2009313912B2 (en) | 2015-04-16 |
US7998488B2 (en) | 2011-08-16 |
CN102215866A (zh) | 2011-10-12 |
EP2358387A1 (en) | 2011-08-24 |
CA2747918C (en) | 2018-10-02 |
AU2009313912A1 (en) | 2010-05-20 |
US20120201847A1 (en) | 2012-08-09 |
EP2358387B1 (en) | 2017-04-19 |
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WO2010056991A8 (en) | 2010-07-08 |
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