JP2013525474A - ワクチンとして使用される無毒化大腸菌易熱性エンテロトキシン(lt)との多糖結合 - Google Patents
ワクチンとして使用される無毒化大腸菌易熱性エンテロトキシン(lt)との多糖結合 Download PDFInfo
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- A61K39/02—Bacterial antigens
- A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
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- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
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Abstract
【選択図】 なし
Description
CFU:コロニー形成単位
ELISA:酵素結合免疫吸着測定法
Hib:インフルエンザ菌b型
IEF:等電点電気泳動
LT:易熱性エンテロトキシン
MALLS:多角度レーザー光散乱
OD:光学密度
PNPS:肺炎球菌多糖
PRP:ポリリボシルリビトールリン酸
PS:多糖
SDS−PAGE:ドデシル硫酸ナトリウムポリアクリルアミドゲル電気泳動法
SEC_HPLC:サイズ排除高圧液体クロマトグラフィー
RI:反射率(reflective index)
[0037]さまざまな可能性のある結合プロセスが、図面の図3に図示されている。本発明に従って選択された還元アミノ化プロセスの一般化されたフローチャートは、Glyconjugate J. 1989年、6:489頁に見出され、図面の図4として再現されている。
[0053]ニュージーランドシロウサギを、意図されたヒト用量の多糖、LTS61Kと混合した多糖、又は多糖−LTS61K結合体を用いて、2週間間隔で3回、筋肉内免疫感作して結合体ワクチンの効力を評価した。全てのワクチン調製物は、AlPO4又は他の関連アジュバントを含有しなかった。全てのワクチンの免疫応答は、抗多糖抗原特異的IgG力価を検出するためのELISA、及び抗体の機能的活性を検出するための血清殺菌アッセイにより決定した。試験結果は、結合に成功した多糖−LTS61Kワクチンのみが、多糖単独又はLTS61Kと混合された多糖のみよりも、血清中で高い多糖特異的IgG抗体力価及び大きい殺菌活性を誘導できることを示した。動物免疫原性試験は、LTS61Kタンパク質を含む無毒化大腸菌易熱性エンテロトキシンホロ毒素が、多糖抗原の特異的免疫応答を著しく刺激するのに多糖の担体タンパク質として有用であることを示唆している。
[0068]試験結果を、図面の図20〜23及び表3〜5を参照して以下に記載する。
Claims (20)
- ワクチンとして有用な多糖及び無毒化大腸菌易熱性エンテロトキシン(LT)の結合体。
- 感染性細菌の影響に対して防御又は免疫感作するための、請求項1に記載の結合体。
- 感染性細菌がインフルエンザ菌又は肺炎連鎖球菌である、請求項1に記載の結合体。
- (LT)が変異体タンパク質LT61を含む、請求項1に記載の結合体。
- (LT)が変異体タンパク質LTS61Kを含む、請求項1に記載の結合体。
- 多糖がポリリボシルリビトールリン酸である、請求項1に記載の結合体。
- 精製された請求項1に記載の結合体を含む、哺乳動物に投与するためのワクチン。
- 精製された請求項4に記載の結合体を含む、哺乳動物に投与するためのワクチン。
- 精製された請求項5に記載の結合体を含む、哺乳動物に投与するためのワクチン。
- 精製された請求項1に記載の結合体を含むワクチンの有効量を投与するステップを含む、感染性細菌の影響から哺乳動物を防御又は免疫感作する方法。
- 精製された請求項5に記載の結合体を含むワクチンの有効量を投与するステップを含む、感染性細菌の影響から哺乳動物を防御又は免疫感作する方法。
- 多糖を過ヨウ素酸酸化する工程と、それに続いて、得られた多糖及び(LT)種を還元アミノ化する工程と、得られた結合体を単離する工程と、を含む、ポリリボシルリビトールリン酸及び感染性細菌の変異体タンパク質抗原(LT)を結合させる方法。
- 変異体タンパク質抗原(LT)種がLTS61Kを含む、請求項12に記載の方法。
- インフルエンザ菌b型又は肺炎連鎖球菌の細菌莢膜多糖抗原及び変異体タンパク質LTS61Kの共有結合体。
- インフルエンザ菌b型又は肺炎連鎖球菌の細菌莢膜多糖抗原を還元アミノ化に供するステップと、得られた共有結合体を次いで単離するステップとを含む、多糖及びLTS61Kの共有結合体を生成する方法。
- PRP:LTのモル比の範囲が約3:1〜約60:1の間であり、モル/モルIO4/PRPが約0.1〜約0.4の間である、請求項14に記載の方法。
- 精製された請求項1に記載の結合体を含むワクチンの有効量を投与するステップを含む、旅行者下痢の影響から哺乳動物を防御又は免疫感作する方法。
- 精製された請求項1に記載の結合体を含むワクチンの有効量を投与するステップを含む、腸管毒素原性大腸菌由来の下痢の影響から哺乳動物を防御又は免疫感作する方法。
- 精製された請求項4に記載の結合体を含むワクチンの有効量を投与するステップを含む、下痢の影響から哺乳動物を防御又は免疫感作する方法。
- 精製された請求項5に記載の結合体を含むワクチンの有効量を投与するステップを含む、下痢の影響から哺乳動物を防御又は免疫感作する方法。
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EP2566508A4 (en) | 2013-10-09 |
JP5967585B2 (ja) | 2016-08-10 |
TW201406389A (zh) | 2014-02-16 |
WO2012023008A3 (en) | 2012-05-24 |
EP2566508B1 (en) | 2015-07-22 |
JP2015071630A (ja) | 2015-04-16 |
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CN102858370A (zh) | 2013-01-02 |
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