JP2015530410A - B型肝炎ウイルスコアタンパク質および表面抗原タンパク質をコードする核酸分子ならびにそれを含むワクチン - Google Patents
B型肝炎ウイルスコアタンパク質および表面抗原タンパク質をコードする核酸分子ならびにそれを含むワクチン Download PDFInfo
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Abstract
Description
1.定義
2.ワクチン
a.HBV Core抗原
b.HBV表面抗原
c.HBVコアおよび表面抗原の組み合わせ
d.ワクチン構築物およびプラスミド
e.ワクチンの医薬組成物
f.ワクチン送達の方法
g.アジュバントを用いたワクチンの送達
h.ワクチンを用いて免疫応答を生成する方法
i.ワクチンを用いた治療方法
3.投与経路
a.電気穿孔
4.ワクチンを調製する方法
実施例1
HBVコアタンパク質
1.コンセンサスコア抗原の構築および発現
2.マウスの免疫化
実施例2
HBV表面タンパク質
1.HBsAg DNAワクチン設計
2.多重HBsAg DNAワクチンのインビトロ発現
実施例3
小型動物モデルにおける個々の合成HBsAg DNAプラスミドの免疫原性
1.抗体ELISAアッセイ
2.IFN−γ ELISPOT
3.HBV表面抗原(15−mer)ペプチドマッピング
実施例4
ワクチン接種されたマウスの肝臓および脾臓においてみられる細胞傷害性アッセイおよび抗原特異的CTL
実施例5
HBsAg−HBcAg DNAカクテルの免疫原性
実施例6
カクテルでのアカゲザルの免疫化は、強い細胞性HBc特異的およびHBs特異的免疫応答ならびに液性HBs特異的免疫応答を誘導する
1.ワクチン接種
2.試料採取
実施例7
実施例8
肝臓血液化学パネルを使用した、ワクチン接種後の非ヒト霊長類における肝臓機能の分析
Claims (44)
- ワクチンであって、
(a)配列番号10、配列番号14、配列番号10の完全長アミノ酸配列のアミノ酸配列の全長にわたって95%同一であるタンパク質、および配列番号14の完全長アミノ酸配列のアミノ酸配列の全長にわたって95%同一であるタンパク質からなる群から選択される、1つ以上のタンパク質をコードする核酸分子、または
(b)配列番号12、配列番号16、配列番号12の完全長アミノ酸配列のアミノ酸配列の全長にわたって95%同一であるタンパク質、および配列番号16の完全長アミノ酸配列のアミノ酸配列の全長にわたって95%同一であるタンパク質からなる群から選択される、1つ以上のタンパク質をコードする核酸分子、
を含む、ワクチン。 - (c)配列番号2、配列番号4、および配列番号6からなる群から選択される、1つ以上のタンパク質をコードする核酸分子をさらに含む、請求項1に記載のワクチン。
- (a)配列番号10、配列番号14、配列番号10の完全長アミノ酸配列のアミノ酸配列の全長にわたって95%同一であるタンパク質、および配列番号14の完全長アミノ酸配列のアミノ酸配列の全長にわたって95%同一であるタンパク質からなる群から選択される、1つ以上のタンパク質をコードする核酸分子、
(b)配列番号12、配列番号16、配列番号12の完全長アミノ酸配列のアミノ酸配列の全長にわたって95%同一であるタンパク質、および配列番号16の完全長アミノ酸配列のアミノ酸配列の全長にわたって95%同一であるタンパク質からなる群から選択される、1つ以上のタンパク質をコードする核酸分子、ならびに
(c)配列番号2、配列番号4、および配列番号6からなる群から選択される、1つ以上のタンパク質をコードする核酸分子、
を含む、請求項1に記載のワクチン。 - 前記核酸分子が、配列番号1、配列番号3、配列番号5、配列番号9、配列番号11、配列番号13、および配列番号15からなる群から選択される1つ以上のヌクレオチド配列を含む、請求項3に記載のワクチン。
- 前記核酸分子が、プラスミドである、請求項1に記載のワクチン。
- 前記核酸分子が、ウイルス粒子に組み込まれる、請求項1に記載のワクチン。
- アジュバント分子をさらに含む、請求項1に記載のワクチン。
- 前記アジュバントが、IL−12、IL−15、IL−28、またはランテスである、請求項7に記載のワクチン。
- 請求項1に記載のワクチンを対象に投与することを含む、HBV抗原に対する免疫応答を誘導する方法。
- 請求項1に記載のワクチンを対象に投与することを含む、HBV感染から対象を保護する方法。
- 請求項1に記載のワクチンを対象に投与することを含む、HBV感染と診断されている対象を保護する方法。
- 配列番号2を含むタンパク質、配列番号2の完全長アミノ酸配列のアミノ酸配列の全長にわたって95%同一であるタンパク質、少なくとも20個のアミノ酸である配列番号2を含むタンパク質の免疫原性フラグメント、ならびに少なくとも20個のアミノ酸である配列番号2のアミノ酸配列の全長にわたって95%同一であるタンパク質の免疫原性フラグメントからなる群から選択される、1つ以上のタンパク質をコードするコード配列を含む、核酸分子。
- 前記タンパク質のN末端に連結されるシグナルペプチドをさらに含む、請求項12に記載の核酸分子。
- 配列番号2、配列番号4、および配列番号6からなる群から選択される1つ以上のタンパク質をコードする、請求項12に記載の核酸分子。
- 配列番号1を含む核酸配列、配列番号1のアミノ酸配列の全長にわたって98%同一である核酸配列、配列番号1によってコードされる少なくとも20個のアミノ酸を含む免疫原性フラグメントをコードする核酸配列を含むそのフラグメント、ならびに配列番号1によってコードされるタンパク質のアミノ酸配列の全長にわたって98%同一であるタンパク質の少なくとも20個のアミノ酸を含む免疫原性フラグメントをコードする核酸配列を含むそのフラグメントからなる群から選択される、1つ以上の配列を含む、請求項12に記載の核酸分子。
- 前記核酸配列の5’末端に連結されるシグナルペプチドをさらに含む、請求項12に記載の核酸分子。
- 配列番号1、配列番号3、および配列番号5からなる群から選択される1つ以上のヌクレオチド配列を含む、請求項12に記載の核酸分子。
- 前記核酸分子がプラスミドである、請求項12に記載の核酸分子。
- 前記核酸分子が発現ベクターであり、前記もう1つのタンパク質をコードする配列が調節エレメントに動作可能に連結される、請求項12に記載の核酸分子。
- 前記核酸分子が、ウイルス粒子に組み込まれる、請求項12に記載の核酸分子。
- 前記核酸分子が、少なくとも60個のアミノ酸である配列番号2を含むタンパク質の免疫原性フラグメント、および少なくとも60個のアミノ酸である配列番号2のアミノ酸配列の全長にわたって98%同一であるタンパク質の免疫原性フラグメントからなる群から選択される、1つ以上のタンパク質をコードするコード配列を含む、請求項12に記載の核酸分子。
- 前記核酸分子が、少なくとも120個のアミノ酸である配列番号2を含むタンパク質の免疫原性フラグメント、および少なくとも120個のアミノ酸である配列番号2のアミノ酸配列の全長にわたって98%同一であるタンパク質の免疫原性フラグメントからなる群から選択される、1つ以上のタンパク質をコードするコード配列を含む、請求項12に記載の核酸分子。
- 前記核酸分子が、少なくとも180個のアミノ酸である配列番号2を含むタンパク質の免疫原性フラグメント、および少なくとも180個のアミノ酸である配列番号2のアミノ酸配列の全長にわたって98%同一であるタンパク質の免疫原性フラグメントからなる群から選択される、1つ以上のタンパク質をコードするコード配列を含む、請求項12に記載の核酸分子。
- 請求項12に記載の核酸分子を個体に投与することを含む、HBV抗原に対する免疫応答を誘導する方法。
- 請求項12に記載の核酸分子を個体に投与することを含む、個体をHBV感染から保護する方法。
- 請求項12に記載の核酸分子を個体に投与することを含む、HBV感染と診断されている個体を保護する方法。
- タンパク質であって、
(a)配列番号2、
(b)配列番号2に示される完全長配列のアミノ酸配列の全長にわたって95%同一であるタンパク質、
(c)配列番号2の20個以上のアミノ酸を含む配列番号2の免疫原性フラグメント、
(d)20個以上のアミノ酸を含む配列番号2のアミノ酸配列の全長にわたって95%同一であるタンパク質の免疫原性フラグメントからなる群から選択される、タンパク質。 - 前記タンパク質が、少なくとも60個のアミノ酸である配列番号2を含むタンパク質の免疫原性フラグメント、および少なくとも60個のアミノ酸である配列番号2のアミノ酸配列の全長にわたって98%同一であるタンパク質の免疫原性フラグメントからなる群から選択される、請求項27に記載のタンパク質。
- 前記タンパク質が、少なくとも120個のアミノ酸である配列番号2を含むタンパク質の免疫原性フラグメント、および少なくとも120個のアミノ酸である配列番号2のアミノ酸配列の全長にわたって98%同一であるタンパク質の免疫原性フラグメントからなる群から選択される、請求項27に記載のタンパク質。
- 前記タンパク質が、少なくとも180個のアミノ酸である配列番号2を含むタンパク質の免疫原性フラグメント、および少なくとも180個のアミノ酸である配列番号2のアミノ酸配列の全長にわたって98%同一であるタンパク質の免疫原性フラグメントからなる群から選択される、請求項27に記載のタンパク質。
- 請求項27に記載の核酸分子を個体に投与することを含む、HBV抗原に対する免疫応答を誘導する方法。
- 請求項27に記載の核酸分子を個体に投与することを含む、個体をHBV感染から保護する方法。
- 請求項27に記載の核酸分子を個体に投与することを含む、HBV感染と診断されている個体を保護する方法。
- 核酸分子であって、
(a)配列番号10、配列番号12、配列番号14、または配列番号16を含む、タンパク質、
(b)配列番号10、配列番号12、配列番号14、または配列番号16のアミノ酸配列の全長にわたって98%同一であるタンパク質、
(c)少なくとも20個のアミノ酸である配列番号10、配列番号12、配列番号14、または配列番号16を含む、タンパク質の免疫原性フラグメント、ならびに
(d)少なくとも20個のアミノ酸である配列番号10、配列番号12、配列番号14、または配列番号16のアミノ酸配列の全長にわたって98%同一であるタンパク質の免疫原性フラグメント、
からなる群から選択される、1つ以上のタンパク質をコードするコード配列を含む、核酸分子。 - (a)配列番号9、配列番号11、配列番号13、または配列番号15を含む核酸配列、
(b)配列番号9、配列番号11、配列番号13、または配列番号15のアミノ酸配列の全長にわたって98%同一である核酸配列、
(c)配列番号9、配列番号11、配列番号13、または配列番号15によってコードされる少なくとも20個のアミノ酸を含む、免疫原性フラグメントをコードする核酸配列を含むそのフラグメント、ならびに
(d)配列番号9、配列番号11、配列番号13、または配列番号15によってコードされるタンパク質のアミノ酸配列の全長にわたって98%同一であるタンパク質の少なくとも20個のアミノ酸を含む免疫原性フラグメントをコードする核酸配列を含むそのフラグメント、
からなる群から選択される、1つ以上の配列を含む、請求項34に記載の核酸分子。 - 前記核酸分子がプラスミドである、請求項34に記載の核酸分子。
- 前記核酸分子が発現ベクターであり、前記1つ以上のタンパク質をコードする配列が調節エレメントに動作可能に連結される、請求項34に記載の核酸分子。
- 前記核酸分子が、ウイルス粒子に組み込まれる、請求項34に記載の核酸分子。
- 請求項34に記載の核酸分子を対象に投与することを含む、HBV抗原に対する免疫応答を誘導する方法。
- 請求項34に記載の核酸分子を対象に投与することを含む、HBV感染から対象を保護する方法。
- 請求項34に記載の核酸分子を対象に投与することを含む、HBV感染と診断されている対象を保護する方法。
- タンパク質であって、
(a)配列番号10、配列番号12、配列番号14、または配列番号16、
(b)配列番号10、配列番号12、配列番号14、または配列番号16のアミノ酸配列の全長にわたって98%同一であるタンパク質、
(c)20個以上のアミノ酸を含む、配列番号10、配列番号12、配列番号14、または配列番号16の免疫原性フラグメント、ならびに
(d)20個以上のアミノ酸を含む、配列番号10、配列番号12、配列番号14、または配列番号16のアミノ酸配列の全長にわたって98%同一であるタンパク質の免疫原性フラグメント、
からなる群から選択される、タンパク質。 - 対象におけるHBVに対する免疫応答の生成に有用なワクチンであって、
請求項34に記載の核酸分子と、
アジュバント分子と、を含む、ワクチン。 - 前記アジュバントが、IL−12、IL−15、IL−28、またはランテスである、請求項43に記載のワクチン。
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