JP2007125039A - ニワトリ貧血因子ワクチン - Google Patents
ニワトリ貧血因子ワクチン Download PDFInfo
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- JP2007125039A JP2007125039A JP2007025127A JP2007025127A JP2007125039A JP 2007125039 A JP2007125039 A JP 2007125039A JP 2007025127 A JP2007025127 A JP 2007025127A JP 2007025127 A JP2007025127 A JP 2007025127A JP 2007125039 A JP2007125039 A JP 2007125039A
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
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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
- A61K39/12—Viral antigens
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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
- A61P31/12—Antivirals
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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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5252—Virus inactivated (killed)
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
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- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2720/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsRNA viruses
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
【解決手段】ワクチンのCAAウイルスは孵化卵内における連続継代により弱毒化する。この発明はまた、このような新規のCAAウイルスおよび該ウイルスの製造方法も提供する。インビトロにおいてCAAウイルスを高力価に増殖させることができ、得られたウイルスは免疫原性を保持し且つ病原性も極めて低い。これにより、該ワクチンは、CAAに対する家禽類の保護に有効である。
【選択図】なし
Description
‐これまでに開示されている全てのCAA株に対立するものとして、そのCAAウイルスは胚中において致死的または病理学的作用を含む、CAAに特異的な病変を誘導する。(Yuasa、N.ら、1979年、上掲;Yuasa、N.及びYoshida、I.、1983年、上掲;Bulow von、V.及びWitt、M.、1986年、上掲)。他の好ましい特性は、
‐このCAAウイルスは弱毒化され、つまり、1日令のSPFニワトリに投与する場合、野外から単離したCAAに関して顕著に低い病原的兆候を誘発するにすぎない、
‐このCAAウイルスは、孵化卵中において高力価にまで増殖するのに適合している。
孵化卵内でのCAAの弱毒化
親株であるインターベット株26P4を、貧血を患っている野生のニワトリの肝臓から単離した(exp. VIM‐CA‐89‐4‐153)。単離後、その株を、卵内に接種する前にMDCC‐MSB1細胞内で5回継代した。卵の卵黄嚢内に、0.2mlのCAA株26P4もしくはGifu(Yuasa、N.ら、Avian Diseases 23巻、366‐385ページ、1979年)を接種した。13日間の100°Fでのインキュベーションの後(湿度:55%)、胚を取り出し、更に、ホモジナイズした。このホモジネートを2500gで10分間遠心した。上清を集め、更に、100μmのフィルターを通して濾した。このホモジネートをトリプトース2.5%で20倍に希釈し、更に、卵当たり0.2mlを接種した。同様に処理することにより、19回より多い回数の継代を、株26P4に施した。この株の19回目の卵継代の試料(CAAの種親(master seed)18‐09‐1990;1ml/fl)を、受託番号I‐1141として、パスツール研究所(パリ、フランス)のCNCMに寄託した。Gifu株を、孵化卵内で14回継代することにより弱毒化した。
2種類の高卵継代CAAウイルスと低卵継代CAAウイルスの孵化ニワトリ卵内における増殖特性の比較
30から60個のSPF卵の卵黄嚢内に、様々な卵継代レベルのウイルスを接種した。100°Fでの7日間のインキュベーションの後(湿度55%)、卵に燭光をあて、死んだ孵化卵もしくは未受精卵は廃棄した。接種後(p.i.)7日目から、卵を毎日燭光をあて、胚死亡率を記録した。CAAに起因する胚死の記録は、接種後10日後、つまり11日目に開始した。接種後13日目に胚を取り出し、ホモジナイズし、更に、2500gで10分間遠心した。上清を集め、MDCC‐MSB1細胞内でウイルス感染を測定した。
CAA生ワクチンでの実験的ワクチン接種
CAAウイルスの弱毒化及び、孵化卵を通してのウイルスの継代による免疫原性の維持を測定するために実験を行った。
実験1においては、以下に示すインターベット株の継代レベルを使用した:
* 1回目の卵継代レベル(低卵継代レベル)
* 18回目の卵継代レベル(高卵継代レベル)
* 未感染のSPF孵化卵からの胚ホモジネート(13日間インキュベーシンしたもの)。
* 4回目の卵継代レベル(低卵継代レベル)
* 19回目の卵継代レベル(高卵継代レベル)
19回目の継代レベルのCAAウイルスを「種親」として貯蔵した。
* 1回目の卵継代レベル
* 14回目の卵継代レベル
107羽の1日齢のニワトリを35〜46羽の3つの群に分けた(上述を参照せよ)。3番目の群はワクチン接種しなかった(対照群)。ワクチン接種後10及び14日目に、群当たり10羽の鳥を、ヘマトクリット値測定及び検死のため隔離室(isolator)から取りだした。ワクチン接種後3週間後に鳥を脱血し、更に、間接免疫蛍光法テスト(IIFT)によりCAA抗体について血清を調べた。ワクチン接種は、実験1及び2について記載したように行った。
96穴マイクロプレート(組織培養グレード)を用いて、MDCC‐MSB1細胞内でウイルスを滴定した。ウイルスの連続した10倍希釈液を、10%のウシ胎児血清及び抗生物質を補充したRPMI1640培地内で調整した。96穴マイクロプレートの10穴を、各ウイルス希釈液の穴当たり100μlで満たした。その後、100μlのMDCC‐MSB1細胞(終濃度は1ml当たり6×105 細胞である)を添加した。その細胞を2、3日毎に二次培養し、更に、10回の二次培養後に終点を読み取った。感染力価をReed及びMuench(Reed、L.J.及びMuench、H.、Am. J. Hyg. 27巻、493‐497ページ、1938年)に従い計算した。
CAAに対する抗体を、96穴のマイクロプレートを使用し、MDCC‐MSB1細胞及び従来の定常ウイルスを用いてVNテスト、改良した血清法により測定した。(Kunitoshi、I.、及びYuasa、N.、Jpn. J. Vet. Sci. 52巻、873‐875ページ、1990年)。IIFTは、標準的な方法に従って行った(Yuasa、N.ら、Avian Pathology 14巻、521‐530ページ、1985年)。
血液は、羽の血管からヘパリン処理マイクロヘマトクリット毛細管内へ採取した。ヘマトクリット値(%)は、12,000rpmで5分間の遠心の後読み取った。ニワトリは、27.0%を下回るヘマトクリット値を示す場合に貧血であると見なされる(Yuasa、N.ら、1979年、上掲)。
表5は、Gifu株の免疫原性はCAAウイルスの弱毒化の結果として悪影響を受けなかったことを証明している。表6は、実験1及び2の血清学の結果を示している。高継代ウイルスの病原性の低下にも拘わらず、このウイルスの免疫原性の低下は何ら認められなかった。
配合生ワクチンでのワクチン接種
レオウイルスワクチン:市販の(インターベット インターナショナル B.V.、オランダ)レオ生ワクチン Nobilis(登録商標)(バッチ 016901)。このワクチンを製造元の推奨により希釈剤で希釈した。
不活性化CAAワクチンでの実験的ワクチン接種
4週齢のSPFニワトリに、油中水型の乳化剤(w/o)中で不活性化したCAAワクチンを筋肉内注射によりワクチン接種した。そのワクチンは、インターベット株の19回目の卵継代レベルの胚ホモジネートから調製した。そのウイルスをβ‐プロピオラクトンで、37℃で3時間不活性化した。50%の不活性化したCAA‐卵材料と50%の鉱物油‐乳化液を含むw/o乳化液を調製した。
Claims (14)
- ニワトリ胚において病変を誘発することができるニワトリ貧血因子(CAA)ウイルス。
- ウイルスがパスツール研究所のCNCMに寄託してあるI‐1141株のものであることを特徴とする、請求項1に記載のCAAウイルス。
- 請求項1または2に記載のCAAウイルスの微生物学的に純粋な組成物。
- 組成物が1ml当たり少なくとも108.0 TCID50を含むことを特徴とする、請求項3に記載の微生物学的に純粋な組成物。
- 弱毒化した生きているCAAウイルスを含む、CAAに対する家禽類の保護のためのワクチンであって、それが請求項1または2に記載のCAAウイルスを含むことを特徴とするワクチン。
- CAAウイルスが孵化卵内において弱毒化されることを特徴とする、請求項5に記載のワクチン。
- CAAに対する家禽類の保護のためのワクチンであって、それが不活性化したCAAウイルスの有効量を含み、そのワクチンはワクチン接種後にニワトリ内においてCAAウイルス中和抗体の産生を誘導することができることを特徴とするワクチン。
- CAAウイルスの前不活性化量が用量当たり少なくとも約107.5 TCID50であることを特徴とする、請求項7に記載のワクチン。
- 前不活性化量が用量当たり少なくとも約108.0 TCID50であり、好ましくは少なくとも約109.0 TCID50であるという特徴を有する、請求項8に記載のワクチン。
- ワクチンが請求項1または2に記載のCAAウイルスを含むことを特徴とする、請求項5〜9のいずれか一項に記載のワクチン。
- ワクチンが更にアジュバントを含むことを特徴とする、請求項7〜10のいずれか一項に記載のワクチン。
- ワクチンが更に1種類またはそれ以上の無関係の鳥類の病原体の抗原を含むことを特徴とする、請求項5または7に記載のワクチン。
- CAAウイルス生成物の製造方法であって、
a)感受性基体に請求項1または2に記載のCAAウイルスを接種し、
b)CAAウイルスを増殖させ、および、
c)CAAウイルスを含有する物質を取り出す
段階を含む方法。 - 基体が孵化卵であることを特徴とする、請求項13に記載の方法。
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EP91202452 | 1991-09-20 |
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JP25137492A Division JP3945830B2 (ja) | 1991-09-20 | 1992-09-21 | ニワトリ貧血因子ワクチン |
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JP2007125039A true JP2007125039A (ja) | 2007-05-24 |
JP4148980B2 JP4148980B2 (ja) | 2008-09-10 |
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JP25137492A Expired - Lifetime JP3945830B2 (ja) | 1991-09-20 | 1992-09-21 | ニワトリ貧血因子ワクチン |
JP2007025127A Expired - Lifetime JP4148980B2 (ja) | 1991-09-20 | 2007-02-05 | ニワトリ貧血因子ワクチン |
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US (1) | US5728569A (ja) |
EP (1) | EP0533294B1 (ja) |
JP (2) | JP3945830B2 (ja) |
KR (1) | KR100221710B1 (ja) |
CN (1) | CN1050302C (ja) |
AT (1) | ATE147632T1 (ja) |
AU (1) | AU659490B2 (ja) |
CA (1) | CA2078605C (ja) |
DE (1) | DE69216732T2 (ja) |
DK (1) | DK0533294T3 (ja) |
ES (1) | ES2099200T3 (ja) |
GR (1) | GR3022755T3 (ja) |
HU (2) | HU217214B (ja) |
MX (1) | MX9205336A (ja) |
NZ (1) | NZ244361A (ja) |
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US5922600A (en) * | 1990-09-12 | 1999-07-13 | Leadd Bv | Chicken anemia virus mutants and vaccines and uses based on the viral proteins VP1 VP2 and VP3 or sequences of that virus coding therefor |
US5981502A (en) * | 1990-09-12 | 1999-11-09 | Leadd B.V. | Methods and compositions for inducing apoptosis in tumor cells |
US6217870B1 (en) | 1990-09-12 | 2001-04-17 | Leadd, Bv | Chicken anemia virus mutants and vaccines and uses based on the viral proteins VP1 VP2 and VP3 or sequences of that virus coding therefor |
NL9301272A (nl) * | 1993-07-20 | 1995-02-16 | Aesculaap Bv | Chicken Anemia Virus mutanten en vaccins en toepassingen gebaseerd op de virale eiwitten VP1, VP2 en VP3 of daarvoor coderende sequenties van dat virus. |
US6071520A (en) * | 1990-09-12 | 2000-06-06 | Leadd Bv | Chicken anemia virus mutants and vaccines and uses based on the viral proteins VP1, VP2 and VP3 or sequences of that virus coding therefor |
GB9414888D0 (en) * | 1994-07-23 | 1994-09-14 | Univ Belfast | Method and composition |
US6270770B1 (en) | 1995-01-06 | 2001-08-07 | Akzo Nobel N.V. | Chicken anaemia agent broiler vaccine |
ZA978434B (en) * | 1996-09-27 | 1998-03-26 | Akzo Nobel Nv | Inactivated vaccines. |
US6159472A (en) * | 1998-11-16 | 2000-12-12 | Akzo Nobel N.V. | Intradermal Avian immunization with inactivated vaccines |
JP2001275664A (ja) * | 2000-02-29 | 2001-10-09 | Akzo Nobel Nv | 低い病原性のニワトリ貧血ウイルス |
US6593134B1 (en) | 2000-03-10 | 2003-07-15 | Cornell Research Foundation, Inc. | Method of propagating chicken infectious anemia virus |
WO2003020308A1 (en) * | 2001-09-05 | 2003-03-13 | Biomune | Chicken anemia virus vaccine from cell line |
MXPA06010131A (es) * | 2004-03-05 | 2007-04-12 | Biomune Company | Vacuna para el virus de la anemia aviar de la linea celular. |
EP1848541A4 (en) * | 2005-02-07 | 2013-01-16 | Pharmalight Inc | METHOD AND DEVICE FOR OPHTHALMIC DELIVERY OF PHARMACEUTICALLY ACTIVE INGREDIENTS |
EP3294876A1 (en) | 2015-05-14 | 2018-03-21 | Merial, Inc. | Method for porcine circovirus production and pcv2 vaccines |
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US3616262A (en) * | 1967-06-09 | 1971-10-26 | Merck & Co Inc | Apparatus and method for propagating viruses i in the extra-embryonic fluids of eggs |
BE853923A (fr) * | 1977-04-25 | 1977-10-25 | Rit Rech Ind Therapeut | Nouveau vaccin vivant ameliore contre le pseudopeste aviaire et son procede de preparation |
US4530831A (en) * | 1982-11-02 | 1985-07-23 | Akzo N.V. | Infectious Bursal Disease vaccine |
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CA2078605A1 (en) | 1993-03-21 |
EP0533294A1 (en) | 1993-03-24 |
GR3022755T3 (en) | 1997-06-30 |
JP3945830B2 (ja) | 2007-07-18 |
MX9205336A (es) | 1993-07-01 |
CA2078605C (en) | 2003-06-17 |
ES2099200T3 (es) | 1997-05-16 |
KR930006150A (ko) | 1993-04-20 |
CN1073879A (zh) | 1993-07-07 |
EP0533294B1 (en) | 1997-01-15 |
KR100221710B1 (ko) | 1999-10-01 |
CN1050302C (zh) | 2000-03-15 |
HU211896A9 (en) | 1995-12-28 |
US5728569A (en) | 1998-03-17 |
HU9202976D0 (en) | 1992-11-30 |
AU2521792A (en) | 1993-03-25 |
HUT65367A (en) | 1994-05-02 |
HU217214B (hu) | 1999-12-28 |
AU659490B2 (en) | 1995-05-18 |
ATE147632T1 (de) | 1997-02-15 |
NZ244361A (en) | 1995-06-27 |
JPH05260962A (ja) | 1993-10-12 |
DE69216732D1 (de) | 1997-02-27 |
TW340873B (en) | 1998-09-21 |
JP4148980B2 (ja) | 2008-09-10 |
ZA927014B (en) | 1993-03-19 |
DE69216732T2 (de) | 1997-06-12 |
DK0533294T3 (da) | 1997-07-07 |
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