JP7401457B2 - ワクチンの効力を決定するための方法 - Google Patents
ワクチンの効力を決定するための方法 Download PDFInfo
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Description
本発明の主題は、ワクチン組成物の相対的な効力を決定するための組成物及び方法を提供することである。免疫化マウスから脾臓細胞を収集し、凍結前に任意にCD138を枯渇させる。ワクチン製剤の効力を決定するために、凍結脾臓細胞の一部を解凍し、次いで、試験ワクチン製剤及び公知の効力の対照ワクチン製剤の段階希釈物を使用して活性化させる。免疫化抗原に特異的な抗体を発現する細胞の数を、希釈物ごとに決定し(場合によっては、抗体を産生する細胞の総数に対して)、得られた用量応答曲線を使用して、前記試験ワクチンの効力を決定する。
以下の説明は、本発明を理解するのに有用であり得る情報を含む。本明細書に記載されている情報のいずれかが、先行技術であるか又は主張されている発明に関連していること、又は具体的若しくは暗黙的に参照されるいずれかの出版物が先行技術であることを認めるものではない。
Claims (20)
- ワクチン製剤の効力を特性決定する方法であって、
参照ワクチンで動物にワクチン接種する工程、
前記動物から脾臓細胞又はB細胞を収集する工程、
前記脾臓細胞又は前記B細胞の第1部分を、第1セットの前記参照ワクチンの段階希釈物に曝露する工程、
前記脾臓細胞又は前記B細胞の第2部分を、第2セットの前記ワクチン製剤の段階希釈物に曝露する工程、
前記第1セットの段階希釈物に対して前記ワクチン製剤の第1抗原に特異的な抗体を発現する、前記第1部分における細胞の第1の数と、前記第1セットの段階希釈物に対して非特異的な抗体を発現する、前記第1部分における細胞の第2の数とを決定する工程、
前記第2セットの段階希釈物に対して前記第1抗原に特異的な抗体を発現する、前記第2部分における細胞の第3の数と、前記第2セットの段階希釈物に対して非特異的な抗体を発現する、前記第2部分における細胞の第4の数とを決定する工程、及び、
前記第1の数を前記第3の数と比較する工程、を含む、方法。 - 前記第2の数を前記第4の数と比較する工程を更に含む、請求項1に記載の方法。
- 前記第1の数及び前記第2の数が、第1の共通の試験表面を使用して決定される、請求項1又は2に記載の方法。
- 前記第3の数及び前記第4の数が、第2の共通の試験表面を使用して決定される、請求項1から3のいずれか1項に記載の方法。
- 前記第1の数が、前記ワクチン製剤の前記第1抗原に特異的な抗体を分泌する細胞に向けられ、かつ、前記第1抗原のアナログ又は前記第1抗原に特異的な第1標識抗体に結合した第1蛍光又は酵素標識を含む第1イムノアッセイを使用して決定され、前記第2の数が、前記ワクチン製剤の前記第1抗原に非特異的な抗体を分泌する細胞に向けられ、かつ、脾臓細胞を提供する種によって産生された抗体に特異的な第2標識抗体に結合した第2蛍光又は酵素標識を含む第2イムノアッセイを使用して決定され、ここで前記第1蛍光又は酵素標識及び前記第2蛍光又は酵素標識が、局在化され識別可能な、請求項1から4のいずれか1項に記載の方法。
- 前記第1イムノアッセイが、抗体プラークアッセイである、請求項5に記載の方法。
- 前記第3の数が、前記ワクチン製剤の前記第1抗原に特異的な抗体を分泌する細胞に向けられ、かつ、前記第1抗原のアナログ又は前記第1抗原に特異的な第3標識抗体に結合した第3蛍光又は酵素標識を含む第3イムノアッセイを使用して決定され、前記第4の数が、前記ワクチン製剤の前記第1抗原に非特異的な抗体を分泌する細胞に向けられ、かつ、脾臓細胞を提供する種によって産生された抗体に特異的な第4標識抗体に結合した第4蛍光又は酵素標識を含む第4イムノアッセイを使用して決定され、ここで前記第3蛍光又は酵素標識及び前記第4蛍光又は酵素標識が、局在化され識別可能な、請求項1から6のいずれか1項に記載の方法。
- 前記比較する工程が、
前記第1セットの段階希釈物の2つ以上のメンバについて、前記第1の数と前記第2の数との間の第1の一連の比率を決定する工程、
前記第2セットの段階希釈物の2つ以上のメンバについて、前記第3の数と前記第4の数との間の第2の一連の比率を決定する工程、
それぞれの希釈物に対する前記第1の一連の比率の第1関数を決定する工程、
それぞれの希釈物に対する前記第2の一連の比率の第2関数を決定する工程、及び、
前記第1関数及び前記第2関数を比較する工程、を含む、請求項2から7のいずれか1項に記載の方法。 - 前記第1関数及び前記第2関数の両方が、勾配関数である、請求項8に記載の方法。
- 前記ワクチン製剤が、更に、第2抗原を含む、請求項1から9のいずれか1項に記載の方法。
- 前記ワクチン製剤の前記第2抗原に特異的な抗体を発現する、前記第1部分における細胞の第5の数を決定する工程、
非特異的抗体を発現する、前記第2部分における細胞の第6の数を決定する工程、及び、
前記第1セットの段階希釈物の少なくとも1つに対する前記第5の数と前記第2の数との間の第3比率を、前記第2セットの段階希釈物の少なくとも1つに対する前記第6の数と前記第4の数との間の第6比率と比較する工程、を更に含む、請求項10に記載の方法。 - 前記第5の数及び前記第2の数が、第1の共通の試験表面を使用して決定される、請求項11に記載の方法。
- 前記第6の数及び前記第4の数が、第2の共通の試験表面を使用して決定される、請求項11又は12に記載の方法。
- 前記第5の数が、前記ワクチン製剤の前記第2抗原に特異的な抗体を分泌する細胞に向けられ、かつ、前記第2抗原のアナログ又は前記第2抗原に特異的な第5標識抗体に結合した第5蛍光又は酵素標識を含む第5イムノアッセイを使用して決定され、前記第2の数が、前記ワクチン製剤の前記第1抗原に非特異的な抗体を分泌する細胞に向けられ、かつ、脾臓細胞を提供する種によって産生された抗体に特異的な第2標識抗体に結合した第2蛍光又は酵素標識を含む第2イムノアッセイを使用して決定され、
ここで前記第5蛍光又は酵素標識及び前記第2蛍光又は酵素標識が、局在化され識別可能な、請求項11から13のいずれか1項に記載の方法。 - 前記第5イムノアッセイが、抗体プラークアッセイである、請求項14に記載の方法。
- 前記第6の数が、前記ワクチン製剤の前記第2抗原に特異的な抗体を分泌する細胞に向けられ、かつ、前記第2抗原のアナログ又は前記第2抗原に特異的な第6標識抗体に結合した第6蛍光又は酵素標識を含む第6イムノアッセイを使用して決定され、前記第4の数が、前記ワクチン製剤の前記第1抗原に非特異的な抗体を分泌する細胞に向けられ、かつ、脾臓細胞を提供する種によって産生された抗体に特異的な第4標識抗体に結合した第4蛍光又は酵素標識を含む第4イムノアッセイを使用して決定され、ここで前記第6蛍光又は酵素標識及び前記第4蛍光又は酵素標識が、局在化され識別可能な、請求項11から15のいずれか1項に記載の方法。
- 前記ワクチン製剤が、予防用ワクチンを含む、請求項1から16のいずれか1項に記載の方法。
- 前記ワクチン製剤が、アデノウイルス、炭疽病、ボツリヌス中毒症、コレラ、ジフテリア、A型肝炎、B型肝炎、C型肝炎、ヘモフィルス・インフルエンザb型菌、ヒト乳頭腫ウイルス、季節性インフルエンザ、日本脳炎、はしか、髄膜炎菌、流行性耳下腺炎、百日咳、肺炎球菌、ポリオ、狂犬病、ロタウイルス、風疹、帯状疱疹、天然痘、破傷風、結核、腸チフス、水痘、及び黄熱病からなるグループの少なくとも1つを対象とするワクチン種を含む、請求項17に記載の方法。
- 前記ワクチン製剤が、治療用ワクチンを含む、請求項1から18のいずれか1項に記載の方法。
- 前記ワクチン製剤が、グリア芽腫、子宮頸癌、皮膚癌、肺癌、乳癌、頭頸部癌、膵臓癌、セリアック病、及び外陰膣カンジダ症からなるグループの少なくとも1つを対象とするワクチン種を含む、請求項19に記載の方法。
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