JP6259831B2 - C型肝炎ウイルスに対するキメラワクチン抗原 - Google Patents
C型肝炎ウイルスに対するキメラワクチン抗原 Download PDFInfo
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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Description
図1で示すように、プラスミドpIMCo64K(配列番号1)、pIME64K(配列番号2)、pIME164K(配列番号3)、pINSE64K(配列番号4)、pIENSb(配列番号5)、pIENS3(配列番号6)、pIMP1E64K(配列番号7)、pIME64Kb(配列番号8)を入手した。これらのプラスミドはそれぞれ、図2に表されるキメラ抗原Coq1(配列番号9)、Eq1(配列番号10)、E1q1(配列番号11)、NSEq2(配列番号12)、EqNSb(配列番号13)、EqNS3(配列番号14)、EqP1(配列番号15)及びEq1b(配列番号16)の大腸菌(Escherichia coli)における発現を可能にする。全ての場合において、抗原Eq1b(HCV株H77、遺伝子型1aに由来する配列)を除いて、アミノ酸配列はHCV遺伝子型1b分離株に由来する(Gonzalez−Horta EE、Eur Rev Med Pharmacol Sci.、2011年;15(11):1320〜7頁)。
雌のBALB/cマウス、週齢8、体重16〜18g、群当たり17匹の動物を免疫化した。免疫化群は次の通りとした。群1、ミョウバン中に配合したキメラ抗原Coq1;群2、ミョウバン中に配合した抗原E1q1;群3、ミョウバン中に配合した抗原Eq1;群4、ミョウバン(対照群)。全ての場合において、組換え抗原20μgを投与した。0、2及び4週目に、筋肉注射により免疫化を実施した。
雌のBALB/cマウス、週齢8、体重16〜18g、群当たり17匹の動物を免疫化した。免疫化群は次の通りとした。群1、ミョウバン中に配合した抗原Eq1;群2、ミョウバン中に配合した、組換えタンパク質NS3と混合した抗原Eq1(Palenzuela Dら、Biotecnologia Aplicada、2006年;23:94〜98頁);群3、ミョウバン中に配合した組換えタンパク質NS3;群4、ミョウバン(対照群)。全ての場合において、組換え抗原Eq1 20μg及びNS3タンパク質10μgを対応する群に投与した。0、2及び4週目に、筋肉注射により免疫化を実施した。
雌のBALB/cマウス、週齢8、体重16〜18g、群当たり17匹の動物を免疫化した。免疫化群は次の通りとした。群1、ミョウバン中に配合したEq1抗原;群2、DNA免疫化用のプラスミドpIDKE2と混合したEq1抗原(Duenas−Carrera y cols.、Biotechnol Appl Biochem.、2004年;39:249〜55頁)の食塩溶液、;群3、pIDKE2プラスミド及びCo.120タンパク質と混合したEq1抗原(Duenas−Carrera y cols.、Biotecnologia Aplicada、1999年;16(4)、226〜231頁)の食塩溶液;群4、0及び3週目に、pIDKE2プラスミドと混合したCo.120タンパク質の食塩溶液、6週目に、ミョウバン中に配合したEq1抗原の投薬;群5、0、3及び6週目に、pIDKE2プラスミドの食塩溶液;群6、ミョウバン(対照);群7、食塩溶液(対照)。対応する群において、マウスは、キメラEq1抗原20μg及びCo.120組換えタンパク質10μgの投与を受けた。pIDKE2プラスミドの場合、各投薬において100μgを投与した。0、3及び6週目に、筋肉注射により免疫化を実施した。
雌のBALB/cマウス、週齢8、体重16〜18g、群当たり17匹の動物を免疫化した。免疫化群は次の通りとした。群1、ミョウバン中に配合したEq1抗原;群2、0及び2週目に、ミョウバン中に配合したCo.120と、E1.340(Lorenzo LJ y cols.、Biotechnol Appl Biochem、2000年;32(2):137〜143頁)と、E2.680(Martinez−Donato y cols.、Mol Biotechnol.、2007年;35(3):225〜36頁)タンパク質の混合物、4週目に、ミョウバン中に配合したキメラEq1抗原の投薬;群3、0週目に、ミョウバン中に配合したキメラEq1抗原、並びに2及び4週目に、ミョウバン中に配合したタンパク質Co.120、E1.340及びE2.680の混合物の投薬;群4、ミョウバン中に配合したタンパク質Co.120、E1.340、E2.680及びEq1の混合物;群5、ミョウバン中に配合したタンパク質Co.120、E1.340及びE2.680の混合物;群6、ミョウバン(対照)。対応する群において、マウスは、キメラEq1抗原20μg;E1及びE2タンパク質16.7μg並びにCo.120タンパク質0.1μgの投与を受けた。0、2及び4週目に、筋肉注射により免疫化を実施した。
雌のBALB/cマウス、週齢8、体重16〜18g、群当たり17匹の動物を免疫化した。免疫化群は次の通りとした。群1、ミョウバン中に配合したキメラEq1抗原;群2、ミョウバン中に配合したキメラNSEq2抗原;群3、ミョウバン中に配合したキメラEqNSb抗原;群4、ミョウバン中に配合したキメラEqNS3抗原;群5、ミョウバン中に配合したキメラEqP1抗原;群6、ミョウバン(対照)。対応する群において、マウスは、組換えキメラ抗原20μgの投与を受けた。0、2及び4週目に、筋肉注射により免疫化を実施した。
雌のBALB/cマウス、週齢8、体重16〜18g、群当たり17匹の動物を免疫化した。免疫化群は次の通りとした。群1、ミョウバン中に配合したキメラEq1b抗原;群2、ミョウバン中に配合したキメラEq1抗原;群3、ミョウバン(対照)。対応する群において、マウスはキメラ抗原20μgの投与を受けた。0、2及び4週目に、筋肉注射により免疫化を実施した。
Claims (19)
- a)HCVポリタンパク質のE2領域(アミノ酸408〜540)からなる第1の部分と、b)HCVポリタンパク質のE1領域(アミノ酸190〜222)からなる第2の部分と、c)このタンパク質のコア領域(アミノ酸1〜50)からなる第3の部分とをこの特定の順序で含む、C型肝炎ウイルス(HCV)に対するキメラワクチン抗原。
- キメラワクチン抗原のアミノ酸配列が、配列番号10(Eq1抗原)及び配列番号16(Eq1b抗原)からなる群より選択される、請求項1に記載のキメラワクチン抗原。
- 前記配列内に追加で、Tヘルパーリンパ球に特異的なエピトープを少なくとも1つ含むことを特徴とする、請求項1に記載のキメラワクチン抗原。
- Tヘルパーリンパ球に特異的な前記エピトープが、HCV非構造タンパク質のエピトープである、請求項3に記載のキメラワクチン抗原。
- 前記非構造タンパク質がNS3である、請求項4に記載のキメラワクチン抗原。
- キメラワクチン抗原のアミノ酸配列が、配列番号14(EqNS3抗原)であることを特徴とする、請求項5に記載のキメラワクチン抗原。
- Tヘルパーリンパ球に特異的な前記エピトープが人工エピトープである、請求項3に記載のキメラワクチン抗原。
- 前記人工エピトープが、エピトープP1M(配列番号17)及びエピトープP2B(配列番号18)からなる群より選択される、請求項7に記載のキメラワクチン抗原。
- キメラワクチン抗原のアミノ酸配列が、配列番号12(NSEq2抗原)、配列番号13(EqNSb抗原)及び配列番号15(EqP1抗原)からなる群より選択されることを特徴とする、請求項8に記載のキメラワクチン抗原。
- a)HCVポリタンパク質のE2領域(アミノ酸408〜540)からなる第1の部分と、b)HCVポリタンパク質のE1領域(アミノ酸190〜222)からなる第2の部分と、c)HCVポリタンパク質のコア領域(アミノ酸1〜50)からなる第3の部分とをこの特定の順序で含むHCVに対するキメラワクチン抗原;並びに薬学的に許容できる賦形剤及び/又はアジュバントを含むワクチン組成物。
- キメラワクチン抗原が、請求項2から9までのいずれか一項に記載のキメラワクチン抗原である、請求項10に記載のワクチン組成物。
- HCV構造抗原又はHCV NS3抗原の組換えタンパク質変異体を更に含む、請求項10又は11に記載のワクチン組成物。
- 前記HCV構造抗原を発現するDNA免疫化用のプラスミドを更に含む、請求項10又は11に記載のワクチン組成物。
- 前記HCV構造抗原及びHCVの組換えカプシドタンパク質を発現するDNA免疫化用のプラスミドを更に含む、請求項10又は11に記載のワクチン組成物。
- DNA免疫化用のプラスミド、HCV構造抗原の組換えタンパク質、又は両方の混合物をベースとする製剤と一緒に初回/追加免疫スケジュールで投与できる、請求項10又は11に記載のワクチン組成物。
- HCVに特異的な免疫反応を誘導するワクチンを生成するための、請求項1から9までのいずれか一項に記載のキメラワクチン抗原の使用。
- 前記ワクチンが、代用ウイルス攻撃モデルにおいて、in vivoで防御能を有する、請求項16に記載の使用。
- 前記ワクチンが、健常人又はHCV感染患者において免疫反応を誘導する能力がある、請求項16に記載の使用。
- 前記ワクチンが、DNA免疫化用のプラスミド、HCV構造抗原の組換えタンパク質又は両方の混合物をベースとする製剤と一緒に初回/追加免疫スケジュールで投与される、請求項16に記載の使用。
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