WO2016017620A1 - Vaccin contre la salmonelle - Google Patents

Vaccin contre la salmonelle Download PDF

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Publication number
WO2016017620A1
WO2016017620A1 PCT/JP2015/071332 JP2015071332W WO2016017620A1 WO 2016017620 A1 WO2016017620 A1 WO 2016017620A1 JP 2015071332 W JP2015071332 W JP 2015071332W WO 2016017620 A1 WO2016017620 A1 WO 2016017620A1
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WO
WIPO (PCT)
Prior art keywords
salmonella
vaccine
protein
secreted
infection
Prior art date
Application number
PCT/JP2015/071332
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English (en)
Japanese (ja)
Inventor
江口　正浩
小川　洋介
和真 白岩
善弘 下地
英司 大石
Original Assignee
国立研究開発法人農業・食品産業技術総合研究機構
株式会社微生物化学研究所
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by 国立研究開発法人農業・食品産業技術総合研究機構, 株式会社微生物化学研究所 filed Critical 国立研究開発法人農業・食品産業技術総合研究機構
Priority to JP2016538357A priority Critical patent/JPWO2016017620A1/ja
Publication of WO2016017620A1 publication Critical patent/WO2016017620A1/fr

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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
    • A61K39/116—Polyvalent bacterial antigens
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to a Salmonella vaccine comprising a combination of secreted proteins of Salmonella and dead bacteria.
  • Attenuated strain vaccines are not currently commercially available, and killed vaccines consisting exclusively of formalin and heat-killed Salmonella spp. Are used (for example, “Bovine Salmonella bivalent vaccine (Scientific Feed Co., Ltd.). Research institute), “chicken Salmonella inactivation 3 blend, KS (Kyoritsu Pharmaceutical Co., Ltd.)).
  • a vaccine using a culture supernatant of Salmonella spp. Cultured under specific conditions has been reported as a vaccine not using an attenuated strain.
  • Patent Document 1 the culture supernatant of Salmonella cultivated in a medium containing low magnesium and low phosphate under SPI-2 induction conditions is used to spread the whole body of Salmonella infected with birds. It has been disclosed to have a protective effect.
  • the present invention has been made in view of such circumstances, and an object of the present invention is to provide a vaccine having high safety and an excellent protective effect against salmonellosis.
  • the present inventor has intensively studied the use of components other than attenuated strains as the components of Salmonella vaccine.
  • the protein secreted from Salmonella and the killed Salmonella each were administered alone, there was no significant protective effect against Salmonella infection compared to the control treated with no treatment or adjuvant. I was not able to admit.
  • a protein secreted from Salmonella and a killed Salmonella were administered in combination, they exhibited an extremely excellent protective effect against Salmonella infection. This protective effect was observed in all Salmonella infections examined. From these facts, the present inventors have found that the combination of a protein secreted from Salmonella and a killed bacteria of Salmonella is a Salmonella vaccine that has both high safety and excellent effects. As a result, the present invention has been completed.
  • the present invention provides the following aspects.
  • a vaccine for protecting a living body from salmonellosis comprising a combination of a protein secreted from Salmonella and a dead fungus of Salmonella.
  • the protein has a composition of 5 mM KCl, 7.5 mM (NH 4 ) 2 SO 4 , 0.5 mM K 2 PO 4 , 38 mM glycerol, 100 mM Tris-HCl, 30 ⁇ M MgCl 2 , 0.2% glucose, 0.1% casamino acid, pH 5
  • the vaccine according to (1) which is secreted from Salmonella spp. Cultured in a medium of 0.0.
  • a method for protecting a living body from salmonellosis comprising administering the vaccine according to (1) or (2) to a living body infected with Salmonella.
  • the vaccine of the present invention comprising a combination of a protein secreted from Salmonella and killed bacteria of Salmonella as an active ingredient provides an extremely high survival rate even when infected with Salmonella when administered to a living body. I was able to. When the protein secreted from Salmonella was administered alone or when the killed Salmonella was administered alone, no significant effect was observed compared to the control (no treatment or adjuvant administration) Considering that all individuals died, the effect of the vaccine of the present invention is a surprising synergistic effect.
  • the vaccine of the present invention was able to show a protective effect against infection with various Salmonella species having different serotypes. Therefore, it can be widely applied in salmonellosis.
  • the present invention provides a vaccine for protecting a living body from salmonellosis, comprising as an active ingredient a combination of a protein secreted from Salmonella and killed bacteria of Salmonella.
  • the present invention also provides a method for protecting a living body from salmonellosis, wherein the vaccine is administered to a living body infected with Salmonella.
  • “Salmonellosis” in the present invention means an infection caused by Salmonella spp.
  • Examples of “Salmonella spp.” That cause salmonellosis include, but are not limited to, Salmonella enterica subsp.
  • a multivalent vaccine can be obtained using two or more Salmonella species.
  • acidic minimal medium examples include 5 mM KCl, 7.5 mM (NH 4 ) 2 SO 4 , 0.5 mM K 2 PO 4 , 38 mM glycerol, 100 mM Tris-HCl, 30 ⁇ M MgCl 2 , 0.2% glucose, 0.1% casamino acid.
  • a medium having a composition of pH 5.0 can be suitably used.
  • protein is 5 mM KCl, 7.5 mM (NH 4 ) 2 SO 4 , 0.5 mM K 2 PO 4 , 38 mM glycerol, 100 mM Tris-HCl, 30 ⁇ M MgCl 2 , 0.2% glucose, 0.1% casamino acid.
  • ⁇ Is secreted from Salmonella cultivated in a medium of pH 5.0 with a composition of '' means that the protein has the ⁇ property '' that it is secreted from Salmonella cultivated in the medium
  • it does not limit the “acquisition method” of the protein.
  • secreted proteins that do not contribute to the control effect against Salmonellosis may be excluded from the vaccine components.
  • Whether a specific secreted protein contributes to the control effect against salmonellosis is determined by administering a combination of the specific protein and a dead fungus of Salmonella to the mouse, infecting the mouse with Salmonella, It is possible to evaluate by testing the survival rate (see this example).
  • the “dead bacteria” of Salmonella genus used in combination with the secreted protein is, for example, heat treatment, chemical disinfectant treatment, irradiation of radiation or ultraviolet rays, mutation promoting substance It can be prepared by treatment or the like.
  • heat treatment or treatment with formalin which is a chemical disinfectant is preferably used.
  • the dead bacteria may be a mixture of different Salmonella species (for example, a mixture of Salmonella species of different species or different serotypes). This makes it possible to expand the range of Salmonella that can be protected against infection.
  • “including a combination” of a protein secreted from Salmonella and a dead fungus of Salmonella means that the vaccine of the present invention contains a protein secreted from Salmonella and Salmonella. Even in the form of a single agent containing both killed bacteria as active ingredients, a combination of a preparation containing a protein secreted from Salmonella as an active ingredient and a preparation containing Salmonella killed as an active ingredient It means that it may be a form.
  • the vaccine of the present invention may contain a pharmacologically acceptable carrier in addition to the above active ingredients.
  • a pharmacologically acceptable carrier include sterilized water and physiological saline, vegetable oils, solvents, bases, emulsifiers, suspensions, surfactants, stabilizers, flavoring agents, fragrances, excipients, vehicles, preservatives.
  • other additives etc. are mentioned, it is not restrict
  • the active ingredient can be in various forms such as injections, aerosols, capsules, tablets, powders, granules, etc. depending on the administration method and therapeutic purpose.
  • an adjuvant can be further added to enhance the immune response.
  • the adjuvant include Freund's complete adjuvant, Freund's incomplete adjuvant, oil adjuvant, aluminum hydroxide, aluminum phosphate, saponin, and vitamin E, but are not particularly limited as long as the effect is exhibited.
  • the “living body” to which the vaccine of the present invention is administered means living animals and human bodies.
  • the animal is not particularly limited as long as it can be infected by Salmonella, and it may be a domestic animal, a pet animal, a laboratory animal, or any other animal. It may be. Examples of animals include, but are not limited to, cows, pigs, horses, sheep, goats, chickens, ducks, geese, ducks, quails, pheasants, pigeons, turkeys, guinea fowls, dogs, cats and the like.
  • the vaccine of the present invention can be administered to a living body by a known administration route including subcutaneous, intradermal, intravenous, intramuscular, oral, and intranasal immunization to give immunity to the living body.
  • the vaccine preparation of the present invention is a concomitant drug
  • the preparations may be administered at the same time, or may be administered with a time difference within a range that does not diminish the effect of the combination.
  • the dose of the vaccine of the present invention may be an amount that can induce an immune response in a living body, such as the age and weight of animals and humans, the type of animal, the type of pathogenic bacteria (for example, the difference in the degree of pathogenicity, etc.) ), And the method and route of administration.
  • the dose of the secreted protein as the active ingredient is usually 0.05 ⁇ g to 1500 ⁇ g, preferably 5 ⁇ g to 500 ⁇ g.
  • a single dose of dead bacteria as an active ingredient is usually 10 3 to 10 10 and preferably 10 6 to 10 9 as the number of dead bacteria. Administration may be performed multiple times, and the administration interval in this case is usually 1 to 2 weeks.
  • Salmonella spp. Salmonella spp. Salmonella Typhimurium S. Typhimurium
  • Salmonella Choleraesuis S. Choleraesuis
  • Salmonella Dublin S. Dublin belonging to Salmonella enterica subsp. (O9 group) was used.
  • the antibody titer was confirmed by the ELISA method against secreted proteins and dead bacteria within 2 to 6 weeks after immunization. Specifically, secreted protein or dead bacteria were adjusted to 5 ⁇ g / ml and immobilized on a 96 ELISA plate at 100 ⁇ l / well. Next, mouse serum was reacted with the secreted protein on the plate and then reacted with HRP-anti-mouse antibody, followed by color development, and the antibody titer was measured based on the color development. When killed bacteria were administered alone and antibody titer against killed bacteria was not observed, killed bacteria (1 ⁇ 10 4 CFU / 200 ⁇ l PBS) were intravenously injected into mice for booster immunization.
  • An attenuated strain vaccine is known as a Salmonella vaccine with a high infection-protecting effect, but it is not commercially available due to safety issues. From the viewpoint of safety, vaccines using dead bacteria or specific proteins are desirable.
  • the vaccine of the present invention using a combination of a secreted protein and dead bacteria is highly safe and can exert an excellent protective effect against infection with Salmonella on animals such as livestock and humans. Therefore, the vaccine of the present invention can be used particularly in the fields of agriculture and medicine.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Mycology (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)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

Il a été découvert que, lorsqu'une combinaison constituée d'une protéine sécrétée par une bactérie appartenant au genre Salmonella et de cellules mortes d'une bactérie appartenant au genre Salmonella est administrée à un organisme vivant, un excellent effet de défense contre une infection par une bactérie appartenant au genre Salmonella est obtenu par comparaison avec le cas de l'administration uniquement de la protéine, ou uniquement des cellules mortes. Ainsi, l'invention concerne un vaccin qui présente une sûreté élevée et une excellente capacité de défense contre la salmonellose.
PCT/JP2015/071332 2014-07-28 2015-07-28 Vaccin contre la salmonelle WO2016017620A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2016538357A JPWO2016017620A1 (ja) 2014-07-28 2015-07-28 サルモネラワクチン

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2014153121 2014-07-28
JP2014-153121 2014-07-28

Publications (1)

Publication Number Publication Date
WO2016017620A1 true WO2016017620A1 (fr) 2016-02-04

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ID=55217520

Family Applications (1)

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PCT/JP2015/071332 WO2016017620A1 (fr) 2014-07-28 2015-07-28 Vaccin contre la salmonelle

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JP (2) JPWO2016017620A1 (fr)
WO (1) WO2016017620A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020009216A1 (fr) * 2018-07-05 2020-01-09 国立研究開発法人農業・食品産業技術総合研究機構 VACCIN CONTRE LA SALMONELLE UTILISANT UNE PROTÉINE SseJ

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06192126A (ja) * 1992-09-01 1994-07-12 Nisshin Flour Milling Co Ltd 動物のサルモネラ感染症予防・治療剤
JP2006503825A (ja) * 2002-09-03 2006-02-02 フォンダシオン ユーロバク アジュバント
JP2009215226A (ja) * 2008-03-11 2009-09-24 Chemo Sero Therapeut Res Inst 動物用不活化サルモネラ３価ワクチンおよびその調製方法
JP2010501599A (ja) * 2006-08-31 2010-01-21 ザ ユニヴァーシティ オブ ブリティッシュ コロンビア 脊椎動物の被験体におけるサルモネラ種細菌感染症の治療または予防のためのワクチンおよび方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06192126A (ja) * 1992-09-01 1994-07-12 Nisshin Flour Milling Co Ltd 動物のサルモネラ感染症予防・治療剤
JP2006503825A (ja) * 2002-09-03 2006-02-02 フォンダシオン ユーロバク アジュバント
JP2010501599A (ja) * 2006-08-31 2010-01-21 ザ ユニヴァーシティ オブ ブリティッシュ コロンビア 脊椎動物の被験体におけるサルモネラ種細菌感染症の治療または予防のためのワクチンおよび方法
JP2009215226A (ja) * 2008-03-11 2009-09-24 Chemo Sero Therapeut Res Inst 動物用不活化サルモネラ３価ワクチンおよびその調製方法

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020009216A1 (fr) * 2018-07-05 2020-01-09 国立研究開発法人農業・食品産業技術総合研究機構 VACCIN CONTRE LA SALMONELLE UTILISANT UNE PROTÉINE SseJ
JPWO2020009216A1 (ja) * 2018-07-05 2021-07-08 国立研究開発法人農業・食品産業技術総合研究機構 ＳｓｅＪタンパク質を用いたサルモネラワクチン
JP7281208B2 (ja) 2018-07-05 2023-05-25 国立研究開発法人農業・食品産業技術総合研究機構 ＳｓｅＪタンパク質を用いたサルモネラワクチン

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JP6712760B2 (ja) 2020-06-24
JPWO2016017620A1 (ja) 2017-04-27
JP2019199478A (ja) 2019-11-21

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