WO2016155580A1 - 一种无细胞百日破联合疫苗及其制备方法 - Google Patents

一种无细胞百日破联合疫苗及其制备方法 Download PDF

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WO2016155580A1
WO2016155580A1 PCT/CN2016/077416 CN2016077416W WO2016155580A1 WO 2016155580 A1 WO2016155580 A1 WO 2016155580A1 CN 2016077416 W CN2016077416 W CN 2016077416W WO 2016155580 A1 WO2016155580 A1 WO 2016155580A1
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vaccine
pertussis
preparation
acellular
cell
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PCT/CN2016/077416
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English (en)
French (fr)
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陈道远
李洪光
吴强
陈元芬
马礼耕
韩炼
罗力心
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成都欧林生物科技股份有限公司
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Publication of WO2016155580A1 publication Critical patent/WO2016155580A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A61K39/05—Actinobacteria, e.g. Actinomyces, Streptomyces, Nocardia, Bifidobacterium, Gardnerella, Corynebacterium; Propionibacterium
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A61K39/08—Clostridium, e.g. Clostridium tetani
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A61K39/116—Polyvalent bacterial antigens

Definitions

  • the invention belongs to the technical field of vaccine production and preparation, and particularly relates to a cell-free 100-day break combination vaccine and a preparation method thereof.
  • Vaccines currently used in China to plan for immunization against pertussis, diphtheria and tetanus diseases include the Whole Cell Dissociation Vaccine (DTwP) and the Acellular Dissociation Vaccine (DTaP). The difference between the two is that the pertussis in the combined vaccine is different, that is, whole-cell pertussis and acellular pertussis.
  • DTwP Whole Cell Dissociation Vaccine
  • DTaP Acellular Dissociation Vaccine
  • whole-cell pertussis is a combination of an inactivated inactivated agent for pertussis, and is used as an immunization vaccine in combination with an adjuvant.
  • whole-cell DTP vaccines have played an important role in the prevention and control of these three infectious diseases.
  • China also included it in the first batch of nationally planned vaccines.
  • diphtheria toxoid and tetanus toxoid are all purified and purified protein antigens in whole cell vaccination vaccine, and pertussis is whole cell bacteria, it is easy to cause the infection after injection of whole cell baibai broken combination vaccine. Serious adverse reactions caused by toxic components in whooping cough.
  • the acellular pertussis in the cell-free DTP vaccine is mainly obtained by extracting and purifying, removing some toxic substances in the pertussis bacteria which are easy to cause side reactions, and retaining the antigenic components having protective immunity.
  • the acellular pertussis vaccine can be divided into a co-purified vaccine and a component purified vaccine from the production process.
  • Japan was the first country to develop a cell-free DTP vaccine.
  • Japan took the lead in the development of a cell-free DTP vaccine containing pertussis toxin (PT) and filamentous hemagglutinin (FHA) using a co-purification process.
  • the process includes culturing the bacteria in the fermenter, salting out the precipitate, and then removing the impurities by sucrose density gradient centrifugation to collect the active ingredients rich in PT and FHA.
  • China's cell-free DTP vaccine was developed in the mid-1980s, and the production number was obtained in the mid-1990s.
  • the production process is based on the Japanese co-purification process. In 2011, China incorporated a total of purified cell-free DNA into the immunization program.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Mycology (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

提供了一种无细胞百日破联合疫苗及其制备方法。无细胞百日破联合疫苗由下述组分的原料组成：百日咳毒素：5～40µg；丝状血凝素：5～40µg；百日咳黏附素：2～10µg；白喉类毒素：10～25lf；破伤风类毒素：4～10lf；氢氧化铝：1.0～2.0mg/ml；氯化钠：7.5～9.5g/L。制备方法包括制备各单价疫苗原液、合并和稀释。

Description

一种无细胞百日破联合疫苗及其制备方法 技术领域
本发明属于疫苗生产制备技术领域，具体涉及一种无细胞百日破联合疫苗及其制备方法。
背景技术
百日咳、白喉、破伤风等疾病在我国流行范围广、危害严重，及时进行疫苗接种是有效的预防保护性措施。我国目前应用于计划免疫预防百日咳、白喉和破伤风疾病的疫苗包括全细胞百白破联合疫苗(DTwP)和无细胞百白破联合疫苗(DTaP)。两者区别在于联合疫苗中的百日咳不同，即全细胞百日咳和无细胞百日咳。
顾名思义，全细胞百日咳是将百日咳全菌体用适当灭活剂灭活后，与佐剂配合，直接用作免疫用疫苗。作为最早纳入WHO扩大免疫计划(EPI)的疫苗，全细胞百白破疫苗已经在预防和控制这三种传染病方面发挥了重要作用。我国也在1985年将其纳入第一批国家计划免疫的疫苗。然而，由于全细胞百白破疫苗中白喉类毒素、破伤风类毒素均为提纯精制过的有效蛋白抗原，而百日咳则为全细胞菌体，所以注射全细胞百白破联合疫苗后容易发生因百日咳所含毒性组份引起的严重不良反应。20世纪70年代，由于百日咳发病率的下降以及接种全细胞百白破疫苗(DTwP)后出现的严重的不良反应，英国、荷兰及日本等国家一度出现了抵制疫苗接种及停用的现象，导致接种率下降，致使这些国家百日咳的发病率又出现大幅反弹。我国也因其容易产生副反应，严重影响了计划免疫的实施，使全国免疫覆盖率未真正达到85％，造成过百日咳局部爆发流行的情况，如贵州1997年曾爆发流行。
目前，绝大多数发达国家均已经采用副反应较小的无细胞百白破联合疫苗，作为常规免疫用疫苗，取代传统的全细胞百日咳疫苗。无细胞百白破联合疫苗中的无细胞百日咳主要是通过提取纯化，去掉百日咳菌体中一些易引起副反应的毒性物质，而保留具有保护性免疫作用的抗原成分。
无细胞百日咳疫苗从生产工艺来讲可分为共纯化疫苗和组份纯化疫苗。日本是最早研制出无细胞百白破疫苗的国家。1981年日本率先采用共纯化工艺研制成功含有百日咳毒素(PT)和丝状血凝素(FHA)的无细胞百白破疫苗。其工艺包括发酵罐培养细菌后，盐析沉淀，然后用蔗糖密度梯度离心去除杂质，收集富含PT和FHA的有效成分。我国的无细胞百白破联合疫苗于80年代中期开始研制，90年代中期获得生产文号，生产工艺是沿用日本的共纯化工艺。2011年，我国将共纯化的无细胞百白破纳入免疫接种计划。

Claims (1)

  1. Figure PCTCN2016077416-appb-100001
PCT/CN2016/077416 2015-03-27 2016-03-25 一种无细胞百日破联合疫苗及其制备方法 WO2016155580A1 (zh)

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CN104707134A (zh) * 2015-03-27 2015-06-17 成都欧林生物科技股份有限公司 一种无细胞百日破联合疫苗及其制备方法
CN105106947A (zh) * 2015-07-21 2015-12-02 华兰生物工程股份有限公司 过氧化氢脱毒的无细胞百日咳疫苗及其制备方法
CN106046127A (zh) * 2016-08-10 2016-10-26 成都生物制品研究所有限责任公司 一种白喉类毒素的制备方法
CN109513001A (zh) * 2017-09-18 2019-03-26 辽宁茂康源生物科技有限公司 一种a群c群脑膜炎球菌多糖吸附白喉破伤风联合疫苗及生产工艺
CN111135294A (zh) * 2020-01-19 2020-05-12 北京智飞绿竹生物制药有限公司 一种联合疫苗
CN111298109A (zh) * 2020-03-09 2020-06-19 辽宁成大生物股份有限公司 利用多模式层析介质Capto adhere去除乙脑疫苗制品中残留宿主DNA的方法

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