JP7472019B2 - 狂犬病ウイルスワクチン - Google Patents
狂犬病ウイルスワクチン Download PDFInfo
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- JP7472019B2 JP7472019B2 JP2020524280A JP2020524280A JP7472019B2 JP 7472019 B2 JP7472019 B2 JP 7472019B2 JP 2020524280 A JP2020524280 A JP 2020524280A JP 2020524280 A JP2020524280 A JP 2020524280A JP 7472019 B2 JP7472019 B2 JP 7472019B2
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Classifications
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- A61K39/205—Rhabdoviridae, e.g. rabies virus
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- A—HUMAN NECESSITIES
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- 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
- A61K2039/5256—Virus expressing foreign proteins
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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
- A61K2039/55—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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
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- C12N2760/20011—Rhabdoviridae
- C12N2760/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/20011—Rhabdoviridae
- C12N2760/20071—Demonstrated in vivo effect
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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
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- C12N2770/36141—Use of virus, viral particle or viral elements as a vector
- C12N2770/36143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Description
本出願は、35U.S.C.§119(e)に基づき、2017年11月6日に出願された仮出願U.S.Serial No.62/581,955の優先権を主張するものであり、その内容はその全体が参照により本明細書に組み込まれる。
従って、本発明は、1つ以上の狂犬病ウイルス抗原をコードするベクターを提供する。このようなベクターは、これらのベクターを含む免疫原性組成物に使用することができる。本発明の免疫原性組成物は、ワクチンに使用することができる。本発明の一態様において、ワクチンは、ワクチン接種された対象(例えば、哺乳動物)を狂犬病ウイルスから保護する。このタイプの一実施形態において、ワクチン接種された対象はイヌである。別の実施形態において、ワクチン接種された対象はネコである。このタイプのより特定の実施形態において、ワクチン接種された対象は、飼い猫である。さらに別の実施形態において、哺乳動物はウマ(equine)(例えば、ウマ(horse))である。本発明はさらに、狂犬病及び他の疾患、例えば、他のイヌ、ウマ及び/又はネコの感染症に対する防御免疫を誘導するための組合せワクチンを提供する。本発明の免疫原性組成物及びワクチンの製造及び使用方法も提供される。
本発明はまた、多価ワクチンを提供する。哺乳動物ワクチンにおいて有用な任意の抗原又はそのような抗原の組合せを、ワクチン中、狂犬病ウイルス[例えば、狂犬病糖タンパク質(G)]の哺乳動物抗原をコードする増殖欠損アルファウイルスRNAレプリコン粒子(RP)に添加することができる。したがって、このような多価ワクチンは、本発明に含まれる。
狂犬病糖タンパク質(G)遺伝子はヒトに対してコドン最適化した。得られた遺伝子は、100%のアミノ酸同一性を有するにもかかわらず、生狂犬病ウイルス糖タンパク質(G)配列に対して約85%のヌクレオチド同一性しか有さない。
アルファウイルスRNAレプリコン粒子への狂犬病ウイルス糖タンパク質のコード配列の組み込み
導入
RNAウイルスは、ゲノムに遺伝子操作されたワクチン抗原を導入するためのベクター-ビヒクルとして用いることができる。しかしながら、それらの今日までの使用は、ウイルス抗原をRNAウイルスに組み込み、次いでウイルスをレシピエント宿主に導入することに主に限定されている。その結果、取り込まれたウイルス抗原に対する防御抗体が誘導される。アルファウイルスRNAレプリコン粒子は病原性抗原をコードするために使用されてきた。このようなアルファウイルスレプリコンプラットフォームは、ベネズエラウマ脳炎ウイルス[Pushkoら,Virology、239:389-401(1997)]、シンドビス(SIN)[Bredenbeekら,Journal of Virology、67:6439-6446、(1993)、その内容全体が本明細書に組み込まれる]、及びセムリキフォレストウイルス(SFV)[Liljestrom及びGaroff、Biotechnology(NY)、9:1356-1361(1991)、その内容全体が本明細書に組み込まれる]を含むいくつかの異なるアルファウイルスから開発されている。さらに、アルファウイルスRNAレプリコン粒子は、ブタ及び家禽に対するいくつかの米国農務省認可ワクチンの基礎である。これらには、豚流行性下痢ワクチン、RNA粒子(製品コード19U5.P1)、豚インフルエンザワクチン、RNA(製品コード19A5.D0)、鳥インフルエンザワクチン、RNA(製品コード19O5.D0)、及び処方製品、RNA粒子(製品コード9PP0.00)が含まれる。
ベネズエラウマ脳炎ウイルスの無毒TC-83株のカプシドタンパク質及び糖タンパク質にパッケージされた狂犬病ウイルス由来の狂犬病ウイルス糖タンパク質(G)をコードするアルファウイルスRNAレプリコン粒子を含むワクチンを調製した。狂犬病ウイルスGタンパク質のヌクレオチド配列をヒトに対してコドン最適化した。得られた配列は、100%のアミノ酸同一性を有するにもかかわらず、生狂犬病ウイルス糖タンパク質(G)配列に対して約85%のヌクレオチド同一性しか有さない。ワクチンは、哺乳動物被験体に、例えば、12週齢以上のネコ及びイヌに皮下投与される単回投与として、又は代替的に、一次投与に続いて一回以上の追加投与を含む複数回投与として使用され得る。
ウイルス糖タンパク質をコードするアルファウイルスRNAレプリコン粒子を含有するワクチンのイヌへの投与
RP‐狂犬病ウイルスGワクチン接種後のイヌにおける安全性と血清学的応答を評価するために初期研究を行った。研究のためのRP狂犬病ウイルスGワクチンは、安定剤として5%スクロースと1%イヌ血清中で製剤化され、液体ワクチンは貯蔵のために凍結される。それぞれ5匹のイヌからなる5つの群が、以下のようにワクチン接種を受けた。
ウイルス糖タンパク質をコードするアルファウイルスRNAレプリコン粒子を含有するワクチンのネコへの投与
RP-狂犬病ウイルスGワクチン接種後のネコにおける安全性と血清学的反応を評価するために初期研究を行った。本研究のためのRP狂犬病ウイルスGワクチンを実験用液体安定剤[例えば、米国特許第9,314,519B2号参照]中で製剤化し、2~7℃で冷蔵保存した。以下の表4に要約されるように、4群のネコにワクチン接種を行った。
Claims (12)
- 狂犬病ウイルス糖タンパク質(G)又はその抗原性フラグメントをコードする核酸構築物を含むベネズエラウマ脳炎(VEE)アルファウイルスRNAレプリコン粒子、及び、薬学的に許容される担体を含む、狂犬病ウイルスによる疾患の予防を補助するためのワクチンであって、
ここで、ワクチンは、ワンショットワクチンである、前記ワクチン。 - 前記狂犬病ウイルス抗原が由来するものとは異なる株の狂犬病ウイルスに由来する第2の狂犬病ウイルス抗原をコードする1以上の追加のアルファウイルスRNAレプリコン粒子を含む、請求項1に記載のワクチン。
- 第二の狂犬病ウイルス抗原が、糖タンパク質(G)又はその抗原性フラグメントである、請求項2に記載のワクチン。
- 前記1以上の追加のアルファウイルスRNAレプリコン粒子がVEEアルファウイルスRNAレプリコン粒子である、請求項2又は3に記載のワクチン。
- 狂犬病ウイルス糖タンパク質(G)が、配列番号2のアミノ酸配列と少なくとも95%の同一性を有するアミノ酸配列を含む、請求項1~4のいずれかに記載のワクチン。
- 非ヒト哺乳動物がワクチンで免疫されるときに、非ヒト哺乳動物において抗体が誘導される、請求項1~5のいずれかに記載のワクチン。
- 非ヒト哺乳動物が、イヌ、ネコ、ウマ、フェレット、ヒツジ及びウシからなる群より選択される、請求項6に記載のワクチン。
- 非狂犬病ウイルス病原体に対する防御免疫を誘発するための少なくとも一つの非狂犬病ウイルス抗原をさらに含む、請求項6又は7に記載のワクチン。
- 非狂犬病ウイルス病原体に由来する少なくとも一つのタンパク質抗原又はその抗原性フラグメントをコードするヌクレオチド配列を含むアルファウイルスRNAレプリコン粒子をさらに含む、請求項1~8のいずれかに記載のワクチン。
- 非アジュバント化ワクチンである、請求項1~9のいずれかに記載のワクチン。
- 請求項1~10のいずれかに記載のワクチンの免疫学的に有効な1用量を哺乳動物に投与することを含む、狂犬病ウイルスに対して非ヒト哺乳動物を免疫化する方法。
- 非ヒト哺乳動物が、イヌ、ネコ及びウマの群から選択される、請求項11に記載の方法。
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