JP2019522986A - 弱毒化突然変異体ジカウイルスをコードするゲノム配列 - Google Patents
弱毒化突然変異体ジカウイルスをコードするゲノム配列 Download PDFInfo
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- JP2019522986A JP2019522986A JP2018568193A JP2018568193A JP2019522986A JP 2019522986 A JP2019522986 A JP 2019522986A JP 2018568193 A JP2018568193 A JP 2018568193A JP 2018568193 A JP2018568193 A JP 2018568193A JP 2019522986 A JP2019522986 A JP 2019522986A
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- genomic sequence
- guanine
- adenosine
- repaired
- zika virus
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Abstract
Description
本発明は、弱毒化突然変異体ジカウイルスをコードするゲノム配列に関する。
ジカウイルスは蚊媒介性フラビウイルスであり、1947年にウガンダで、黄熱をモニタリングするネットワークによって、サルにおいて初めて同定された。その後、それは、1952年にウガンダ及びタンザニア連合共和国で、ヒトにおいて確認された。アフリカ、米国、アジア及び太平洋では、ジカウイルス疾患の発生が記録されている。1960年代から1980年代にアフリカ及びアジア全域で、典型的には軽度の病気を伴うヒト感染が見出された。ジカ感染によって引き起こされた疾患の最初の大発生は、2007年にヤップ(ミクロネシア連邦)の島から報告された。2015年7月にブラジルで、ジカウイルス感染とギラン・バレー症候群との間の関連が報告された。2015年10月にブラジルで、ジカウイルス感染と小頭症との関連が報告された。ジカウイルスは、Aedes属、熱帯地方では主にAedes aegyptiの感染蚊によって刺されることで人々に主に伝染される。通常、Aedesの蚊は日中に刺し、早朝及び午後/夕方にピークに達する。これは、ジカウイルス、チクングニャ熱及び黄熱病を伝染する同じ蚊である。ジカウイルスの性的伝染も可能である。輸血などの他の伝染様式が調査されている。通常、ジカウイルス疾患は軽度であり、特定の処置を必要としない。ジカウイルスにかかっている人々は、多くの休息を取り、十分な水分を飲み、普通薬で痛み及び発熱を処置すべきである。症候が悪化した場合、医療及びアドバイスを求めるべきである。現在、利用可能なワクチンはない。WHOの専門家は、妊婦及び出産期の女性で使用するのに安全な弱毒化ワクチン及び他の非生ワクチンの開発を優先すべきであると提案している。
本発明は、特に妊婦のワクチン接種に安全であるという利点を提供する、弱毒化突然変異体ジカウイルスをコードするゲノム配列に関する。特に、本発明者らは、地域流行性ゲノム配列に元々存在していたmiR−4279のためのいくつかの結合部位を修復するために、流行性ゲノム配列の非常に特定の位置においていくつかの特定の置換を導入した。また、本発明者らは、Eタンパク質上のNグリコシル化部位の無効化をもたらす突然変異であって、ギラン・バレー症候群の原因となる自己抗体の生成を防止するであろう突然変異をさらに導入した。本発明者らは、高力価のウイルスを産生する能力に影響を与えずに細胞変性効果の劇的な減少をもたらすウイルスのさらなる突然変異を生産した。
本出願を通して、様々な参考文献により、本発明が関係する技術水準が説明されている。これらの参考文献の開示は、参照により本開示に組み入れられる。
Claims (15)
- miR−4279のための少なくとも1つの結合部位が修復されている配列番号1を特徴とする、ゲノム配列。
- 2707位のアデノシン(A)をチミン(T)で置換し、2713位のグアニン(G)をアデノシン(A)で置換し、2716位のアデノシン(A)をグアニン(G)で置換することによって、第1の結合部位が修復されている、請求項1に記載のゲノム配列。
- 3331位のシチジン(C)をチミン(T)で置換し、3332位のシチジン(C)をチミン(T)で置換し、3343位のシチジン(C)をグアニン(G)で置換することによって、第2の結合部位が修復されている、請求項1に記載のゲノム配列。
- 5106位のグアニン(G)をアデノシン(A)で置換し、5113位のアデノシン(A)をグアニン(G)で置換し、5116位のアデノシン(A)をグアニン(G)で置換することによって、第3の結合部位が修復されている、請求項1に記載のゲノム配列。
- 5962位のシトシン(C)をチミン(T)で置換し、5971位のグアニン(G)をアデノシン(A)で置換することによって、第4の結合部位が修復されている、請求項1に記載のゲノム配列。
- 6211位のアデノシン(A)をグアニン(G)で置換し、6220位のチミン(T)をシチジン(C)で置換することによって、第5の結合部位が修復されている、請求項1に記載のゲノム配列。
- 流行株のゲノム配列において、1つ、2つ、3つ、4つ又は5つの結合部位が修復されている、請求項1に記載のゲノム配列。
- 配列番号2によって表される配列からなる、請求項1に記載のゲノム配列。
- 152位、156位又は158位の少なくとも1つのアミノ酸残基が突然変異されているタンパク質Eをコードする、請求項1に記載のゲノム配列。
- 152位のイソロイシン残基(I)がトレオニン残基(T)で置換されており、156位のトレオニン残基(T)がイソロイシン残基(I)で置換されており、ヒスチジン残基(H)がチロシン残基(Y)で置換されているタンパク質Eをコードする、請求項1に記載のゲノム配列。
- 配列番号3によって表される配列からなる、請求項1に記載のゲノム配列。
- 請求項1に記載のゲノム配列を含む、宿主細胞。
- 請求項1に記載のゲノム配列によってコードされる、弱毒化ジカウイルス。
- 請求項13に記載の弱毒化ジカウイルスを含む、ワクチン組成物。
- 被験体においてジカウイルスに対する免疫応答を誘発するための方法であって、治療有効量の請求項14に記載のワクチン組成物を該被験体に投与することを含む、方法。
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EP3481848B1 (en) | 2021-02-17 |
ES2868627T3 (es) | 2021-10-21 |
JP7046848B2 (ja) | 2022-04-04 |
WO2018007575A1 (en) | 2018-01-11 |
US10590174B2 (en) | 2020-03-17 |
EP3481848A1 (en) | 2019-05-15 |
BR112018077041A2 (pt) | 2019-04-02 |
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