TWI328458B - Subunit vaccine of pasteurella multocida in veterinary uses - Google Patents

Subunit vaccine of pasteurella multocida in veterinary uses Download PDF

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Publication number
TWI328458B
TWI328458B TW096108321A TW96108321A TWI328458B TW I328458 B TWI328458 B TW I328458B TW 096108321 A TW096108321 A TW 096108321A TW 96108321 A TW96108321 A TW 96108321A TW I328458 B TWI328458 B TW I328458B
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Taiwan
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disease caused
pharmaceutical composition
composition according
poultry
animal
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TW096108321A
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English (en)
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TW200836759A (en
Inventor
Poa Chun Chang
jin ru Wu
Happy K Shieh
Jui Hung Shien
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Univ Nat Chunghsing
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Priority to TW096108321A priority Critical patent/TWI328458B/zh
Priority to US12/073,306 priority patent/US8084043B2/en
Publication of TW200836759A publication Critical patent/TW200836759A/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
    • A61K39/102—Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
    • A61K2039/521—Bacterial cells; Fungal cells; Protozoal cells inactivated (killed)
    • 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
    • A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
    • A61K2039/552—Veterinary vaccine
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55505—Inorganic adjuvants
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Immunology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Description

1328458 九、發明說明： 【發明所屬之技術領域】 本發明揭示巴斯德桿菌ww/i〇c/•如脂蛋白Ε (ριρΕ) 用作為次單位疫苗之用途。本發明提供一種包含脂蛋白E為主要成 份之疫苗組成物，該疫苗可用於防治巴斯德桿菌p WMh0cz•如所引 起之感染症，尤其是用作為防治獸醫疾病的次單位疫苗。 【先前技術】
Pasterurella multocida 是屬於巴斯德菌科（PasieureUaceae)， 巴斯德菌屬（尸__//«)’ 其拉丁文為引起很多種動物 疾病的意思。在過去以eMre//flceae的分類地位多變，近來根據 16s— rRNA序列分析，被分出並置於purple ““Μ。 的gamma subgr〇up中，為Gram_negative兼氣性厭氧菌，和腸道 才干菌科同源。户ime㈣//fl則原為動物的病原菌會對許多 的動物造成出血性敗血症〈hem〇rrhagic septicemia〉，因此户 曾有出血性敗血症巴氏桿菌、禽畜出血性敗血症巴氏桿 菌、敗血性巴氏桿菌等中譯名，本菌引起之疾病不只出血性敗血症 種’感染對象亦不侷限在家畜家禽。本菌能造成多種哺乳類及鳥 類發病，文感染之動物引發急性敗血症並導致高度死亡率。八 oczc/α的馆主範圍很廣，常潛伏於哺乳動物與鳥類的上呼吸 道血液、#膜中》P. ^較少感染人類，然而人類被感染 的主因大多疋因為受到帶菌貓、狗的抓傷、咬傷所纟，或如屠宰廠 工人及獸醫暴露於被感染的動物屍體。嚴重感染將引起菌血症骨 趙炎腦膜炎、肺炎。户· 主要感染的動物包括：牛、羊 的,灰性敗血症，火雞、雞、鴨、鵝之家禽霍亂，冑的萎缩性鼻炎 等大部分的/>· Ww/i0Ci•心菌株對老鼠及兔子有高度致病性感染 1328458 劑量在1 -1 0個菌落數（CFU )即可造成急性敗血症狀。 在家禽方面’巴斯德桿菌户如可造成火雞、雞、鴨、 鶴等豕禽之急性敗血性疾病，一旦爆發常引起重大經濟損失。目前 控制家禽霍亂之方法’主要是使用不活化全菌疫苗，但是此種菌苗 缺乏交又A清型保護效力，且施打後常有纖維肉瘤產生，以及造成 雞鴨鶴食您不振’產蛋下降等副作用，故農民使用意願較低。因此 .一旦發生豕禽霍亂病例時多使用抗生素予以控制，但這卻又造成抗 .生素之濫用與消費者對禽畜產品之疑慮。另外在國外雖有馴化活菌 疫田’但可能發生細菌回復毒力而造成疫情之疑慮因此開發新— φ 代之疫苗=防治家禽霍亂，乃為當務之急。 而失j m在牛1的細菌後病琢Mannheiaa haemolytic，有1 PlpE作為次單位疫苗之報告，但該報告之pipE與本發明之 • ?\成’矣今M. haenwjytica之慝名與後名與P. mujtodda宄全 . 不同’而且其於蛋白質序列相似性僅有24. 3% ’二者為不同的蛋 白質’同時’該兩種細菌之宿主與所引起之疾病也不同，另外該
PlpE並未做過任何老鼠與雞隻實驗，也未被學術認為能作為家禽 霍亂。 本發明首先發現巴斯德桿菌p. •心脂蛋白E (pasteureiia hp〇Pr〇tein E，P1PE)可有效用於防治Λ 所引起之感染的 新用途進而研發製付用於防治广所造成之動物疾病的 ••人單位疫田。本發明之次單位疫苗是以大腸桿菌表現的plpE作為 疫苗抗原，與傳統之全菌疫苗不同，而是僅以病原菌單一成分作為 一 抗原的疫苗，因此無產生纖維肉瘤等副作用。另外，本發明之次單 位疫苗施打後可有效保護同源與異源血清型之攻毒感染，其效果優 於傳統菌苗。

Claims (1)

  1. 公令本 月修正本 十、申請專利範g :(修正本) 種用於防/α由巴斯德桿菌P. ww/iocii/a所造成之動物 疾病的次單位疫苗組成物，其特徵在於包含具有與SEQ 2. 5. 6. 7. ID 1至6任一者達9〇%以上相似性之胺基酸序列，且仍 保有相似抗原活性的户.心脂蛋白E (lipoprotein E，PlpE)做為抗原蛋白，及獸醫學上可接受之佐劑。 根據申請專利範圍第1項之疫苗組成物，其中該/>. ww/iocidfl脂蛋白e是具有選自序列表SEQ ID 1至6任 一者中所列之胺基酸序列之蛋白。 根據申請專利範圍第1項之疫苗組成物，其中該由p wWioci’rfa所造成之動物疾病為家禽急性敗血性疾病。 根據申請專利範圍第4項之疫苗組成物，其中該由八 WW/fOCififfl所造成之動物疾病為家禽霍亂病。 根據申請專利範圍第1項之疫苗組成物，其中該由尺 WM"〇CZ’i/e所造成之動物疾病為豬的萎縮性鼻炎。 種用於防治由巴斯德桿菌/>· 心所造成之感染 病或其一或多種相關病症之醫藥組成物，其包含具有與 SEQ ID 1至6任一者達90%以上相似性之胺基酸序列， 且仍保有相似抗原活性的/>. 脂蛋白E (lipoprotein E，PlpE)，及醫藥上可接受之載體或稀釋劑。 根據申請專利範圍第6項之醫藥组成物，其中該由巴斯 德桿菌尸.WMiioc/ί/α造成之感染病為家禽急性敗血性疾 病。 8.根據申請專利範圍第7項醫藥組成物，其中該家禽急性敗 ▲•性疾病為家禽霍亂。 132押8, 9. 根據申明專利範圍第6項之醫藥組成物其中該由巴斯德 桿菌戶· /TJM/iocicfa所造成之感染病係發生於哺乳動物。 10. 根據申請專利範圍第9項之醫藥組成物，其中該鳴乳動 物為鼠類。 11. 根據申請專利範圍第6項之醫藥組成物其中該該尸 mw/ioc/i/a所造成之感染病係引發豬的萎缩性鼻炎。 1328458 H^ 一，圖式：
    粗萃取物經純化 粗萃取物經純化 p年修正替換頁| Crude extrate Purified I in 1 ω lu 2 ω UJ Q- ^ ^Q. Q. K K ο K K iL ii. 〇 iL iL (kDa)M 1 2 3 4 5 170-^: 95一 Π—灯 72 一^卜，厂 γ 56^ ι 43— 繪綠 34—^ ， i‘一 WmBw " ' 20-^# ；. -f ^ '… Crude extrate Purified M 3dld·」·Ladld-」' IOJ13 -mdlchnadld-1-' DDDD k k k k ·73·53 8·6·1·9· "3^-3^^ ㈧ （β) 圓1 〆
TW096108321A 2007-03-09 2007-03-09 Subunit vaccine of pasteurella multocida in veterinary uses TWI328458B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
TW096108321A TWI328458B (en) 2007-03-09 2007-03-09 Subunit vaccine of pasteurella multocida in veterinary uses
US12/073,306 US8084043B2 (en) 2007-03-09 2008-03-04 Subunit vaccine of Pasteurella multocida in veterinary uses

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Application Number Priority Date Filing Date Title
TW096108321A TWI328458B (en) 2007-03-09 2007-03-09 Subunit vaccine of pasteurella multocida in veterinary uses

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TW200836759A TW200836759A (en) 2008-09-16
TWI328458B true TWI328458B (en) 2010-08-11

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* Cited by examiner, † Cited by third party
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US7449178B2 (en) * 2002-04-05 2008-11-11 Merial Limited Attenuated gram negative bacteria
EP3062816B1 (en) 2013-11-01 2020-08-05 Boehringer Ingelheim Animal Health USA Inc. Attenuated pasteurella multocida vaccines & methods of making & use thereof
CN105497885B (zh) * 2014-09-25 2019-02-15 普莱柯生物工程股份有限公司 一种亚单位疫苗及其制备方法和应用
CN113336858B (zh) * 2021-05-20 2024-02-23 江苏省农业科学院 单一位点嵌合巴氏杆菌PlpE抗原表位的兔出血症病毒VP60重组抗原及其制备和应用

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DE60230717D1 (de) * 2002-04-05 2009-02-26 Merial Sas Attenuirte Gram-negative Bakterien

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US8084043B2 (en) 2011-12-27
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