JP7189014B2 - Rsvに対するワクチン - Google Patents
Rsvに対するワクチン Download PDFInfo
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- JP7189014B2 JP7189014B2 JP2018500567A JP2018500567A JP7189014B2 JP 7189014 B2 JP7189014 B2 JP 7189014B2 JP 2018500567 A JP2018500567 A JP 2018500567A JP 2018500567 A JP2018500567 A JP 2018500567A JP 7189014 B2 JP7189014 B2 JP 7189014B2
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- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
- C12N2760/18534—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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Description
特定の実施形態では、リンカーはアミノ酸配列SAIGを含む。
本発明の様々な実施形態を以下に示す。
1.融合前コンフォメーションで安定化される組換え呼吸器合胞体ウイルス(RSV)融合(F)ポリペプチドを含む組成物であって、前記RSV Fポリペプチドは、野生型RSV Fポリペプチドと比較して、少なくとも1つの変異を含み、前記少なくとも1つの変異は、a)486位のアミノ酸のアスパラギン酸(D)の変異、b)489位のアミノ酸のアスパラギン酸(D)の変異、ならびにc)398位のアミノ酸のセリン(S)および/または394位のアミノ酸のリシン(K)の変異からなる群から選択される、組成物。
2.融合前コンフォメーションで安定化される組換え呼吸器合胞体ウイルス(RSV)融合(F)ポリペプチドをコードする核酸配列を含む組成物であって、前記RSV Fポリペプチドは、野生型RSV Fポリペプチドと比較して、少なくとも1つの変異を含み、前記少なくとも1つの変異は、a)486位のアミノ酸のアスパラギン酸(D)の変異、b)489位のアミノ酸のアスパラギン酸(D)の変異、ならびにc)398位のアミノ酸のセリン(S)および/または394位のアミノ酸のリシン(K)の変異からなる群から選択される、組成物。
3.前記核酸配列はベクター中に含まれる、上記2に記載の組成物。
4.前記486位のアミノ酸の前記変異は、アスパラギン酸(D)からアスパラギン(N)への変異である、上記1~3のいずれかに記載の組成物。
5.前記489位のアミノ酸の前記変異は、アスパラギン酸(D)からチロシン(Y)への変異である、上記1~3のいずれかに記載の組成物。
6.前記398位のアミノ酸の前記変異は、セリン(S)からロイシン(L)への変異であり、かつ/または前記394位の変異は、リシン(K)からアルギニン(R)への変異である、上記1~3のいずれかに記載の組成物。
7.前記RSV Fポリペプチドは、完全長RSVタンパク質である、上記1~6のいずれかに記載の組成物。
8.前記RSV Fポリペプチドは、可溶性RSV Fタンパク質である、上記1~6のいずれかに記載の組成物。
9.前記ポリペプチドは、55℃、好ましくは58℃、より好ましくは60℃で少なくとも10分間にわたり安定である、上記1~8のいずれかに記載の組成物。
10.前記ポリペプチドは、配列番号21~26からなる群から選択されるアミノ酸配列を含む、上記1~9のいずれかに記載の組成物。
11.RSV Fタンパク質に対する免疫応答の誘導に使用するための、上記1~10のいずれかに記載の組成物。
12.ワクチンとして使用するための、上記1~11のいずれかに記載の組成物。
13.RSV感染の予防および/または処置に使用するための、上記1~12のいずれかに記載の組成物。
安定な融合前RSV Fポリペプチドの調製
呼吸器合胞体ウイルス(RSV)Fタンパク質に結合する治療小分子は、膜融合を阻害し、準安定なRSV F融合前コンフォメーションの中心空洞内の3重対称ポケットに結合する。阻害剤の結合は、膜融合を促進するには大きい構造転位を受ける必要がある、2つの領域を拘束することにより、このコンフォメーションを安定化させる。本発明によれば、融合前コンフォメーションを逆説的に安定化させるのは、驚くべきことに、エスケープ変異であることがわかった。したがって、本発明によれば、融合前コンフォメーションのRSV Fを安定化させるために、このクラスのエスケープ変異に対応するアミノ酸置換を使用できることが示された。
RSV Fタンパク質A2完全長配列(配列番号1)
RSV Fタンパク質B1完全長配列(配列番号2)
配列番号3
GYIPEAPRDGQAYVRKDGEWVLLSTFL
CR9501重鎖(配列番号16):
CR9501軽鎖(配列番号17):
CR9502重鎖(配列番号18):
CR9502軽鎖(配列番号19):
PreF、RSV A2、フィブリチン(配列番号20)(可溶性、フィブリチンを含む野生型)
PreF、RSV A2、(配列番号21)D486N
PreF、RSV A2、(配列番号22)D489Y
PreF、RSV A2、(配列番号23)S398L、K394R
可溶性PreF、RSV A2、(配列番号24)D486N
可溶性PreF、RSV A2、(配列番号25)D489Y
可溶性PreF、RSV A2、(配列番号26)S398L、K394R
Claims (9)
- 融合前コンフォメーションで安定化される組換え呼吸器合胞体ウイルス(RSV)融合(F)ポリペプチドを含む組成物であって、前記RSV Fポリペプチドは、配列番号1又は配列番号2のアミノ酸配列の野生型RSV Fポリペプチドと比較して変異を有し、前記変異は、486位のアミノ酸のアスパラギン酸(D)からアスパラギン(N)への変異のみからなる、組成物。
- 融合前コンフォメーションで安定化される組換え呼吸器合胞体ウイルス(RSV)融合(F)ポリペプチドをコードする核酸配列を含む組成物であって、前記RSV Fポリペプチドは、配列番号1又は配列番号2のアミノ酸配列の野生型RSV Fポリペプチドと比較して変異を有し、前記変異は、486位のアミノ酸のアスパラギン酸(D)からアスパラギン(N)への変異のみからなる、組成物。
- 前記核酸配列はベクター中に含まれる、請求項2に記載の組成物。
- 前記RSV Fポリペプチドは、完全長RSVタンパク質である、請求項1~3のいずれか一項に記載の組成物。
- 前記RSV Fポリペプチドは、可溶性RSV Fタンパク質である、請求項1~3のいずれか一項に記載の組成物。
- 前記ポリペプチドは、55℃、好ましくは58℃、より好ましくは60℃で少なくとも10分間にわたり安定である、請求項1~5のいずれか一項に記載の組成物。
- RSV Fタンパク質に対する免疫応答の誘導に使用するための、請求項1~6のいずれか一項に記載の組成物。
- ワクチンとして使用するための、請求項1~7のいずれか一項に記載の組成物。
- RSV感染の予防に使用するための、請求項1~8のいずれか一項に記載の組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP15175647 | 2015-07-07 | ||
EP15175647.5 | 2015-07-07 | ||
PCT/EP2016/066098 WO2017005844A1 (en) | 2015-07-07 | 2016-07-07 | Vaccine against rsv |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2018520159A JP2018520159A (ja) | 2018-07-26 |
JP7189014B2 true JP7189014B2 (ja) | 2022-12-13 |
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Application Number | Title | Priority Date | Filing Date |
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JP2018500567A Active JP7189014B2 (ja) | 2015-07-07 | 2016-07-07 | Rsvに対するワクチン |
Country Status (16)
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US (3) | US10456462B2 (ja) |
EP (2) | EP3821906A1 (ja) |
JP (1) | JP7189014B2 (ja) |
KR (1) | KR102638978B1 (ja) |
CN (2) | CN116059336A (ja) |
AU (2) | AU2016289492B2 (ja) |
BR (1) | BR112017027448A2 (ja) |
CA (1) | CA2991002C (ja) |
DK (1) | DK3319633T3 (ja) |
EA (1) | EA039065B1 (ja) |
ES (1) | ES2839880T3 (ja) |
HK (1) | HK1250939A1 (ja) |
IL (2) | IL288541B (ja) |
PL (1) | PL3319633T3 (ja) |
WO (1) | WO2017005844A1 (ja) |
ZA (1) | ZA201800092B (ja) |
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PL3319633T3 (pl) | 2015-07-07 | 2021-04-19 | Janssen Vaccines & Prevention B.V. | Szczepionka przeciwko rsv |
EA201892250A1 (ru) | 2016-04-05 | 2019-03-29 | Янссен Вэксинс Энд Превеншн Б.В. | Вакцина против rsv |
EP3464331B1 (en) | 2016-05-30 | 2020-10-28 | Janssen Vaccines & Prevention B.V. | Stabilized pre-fusion rsv f proteins |
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US11771755B2 (en) | 2018-02-28 | 2023-10-03 | University Of Washington | Self-asssembling nanostructure vaccines |
JP2022513025A (ja) * | 2018-11-13 | 2022-02-07 | ヤンセン ファッシンズ アンド プリベンション ベーフェー | 安定化された融合前rsv fタンパク質 |
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CA3177062A1 (en) | 2020-04-02 | 2021-10-07 | Janssen Vaccines & Prevention B.V. | Stabilized vaccine compositions |
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CN115960214A (zh) * | 2021-10-12 | 2023-04-14 | 中国科学院分子细胞科学卓越创新中心 | 中和呼吸道合胞病毒的全人抗体的设计及应用 |
CN116003536A (zh) * | 2022-09-23 | 2023-04-25 | 暨南大学 | 呼吸道合胞病毒融合前f蛋白突变体及其应用 |
WO2024069420A2 (en) | 2022-09-29 | 2024-04-04 | Pfizer Inc. | Immunogenic compositions comprising an rsv f protein trimer |
WO2024089633A1 (en) | 2022-10-27 | 2024-05-02 | Pfizer Inc. | Rna molecules encoding rsv-f and vaccines containing them |
WO2024089634A1 (en) | 2022-10-27 | 2024-05-02 | Pfizer Inc. | Immunogenic compositions against influenza and rsv |
CN117986382A (zh) * | 2022-11-04 | 2024-05-07 | 北京康乐卫士生物技术股份有限公司 | 针对rsv的重组亚单位疫苗及其应用 |
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