WO2002032453A1 - Vaccin de synthese pour la lutte contre le virus de la peste porcine classique et son procede de preparation - Google Patents

Vaccin de synthese pour la lutte contre le virus de la peste porcine classique et son procede de preparation Download PDF

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Publication number
WO2002032453A1
WO2002032453A1 PCT/CN2001/001188 CN0101188W WO0232453A1 WO 2002032453 A1 WO2002032453 A1 WO 2002032453A1 CN 0101188 W CN0101188 W CN 0101188W WO 0232453 A1 WO0232453 A1 WO 0232453A1
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WO
WIPO (PCT)
Prior art keywords
swine fever
synthetic peptide
epitope
vaccine
polypeptide
Prior art date
Application number
PCT/CN2001/001188
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English (en)
Chinese (zh)
Inventor
Yinghua Chen
Xiaonan Dong
Yi Xiao
Original Assignee
Tsinghua University
Beijing Feikai Biotech Co. Ltd.
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.)
Filing date
Publication date
Application filed by Tsinghua University, Beijing Feikai Biotech Co. Ltd. filed Critical Tsinghua University
Priority to AU2002223384A priority Critical patent/AU2002223384A1/en
Publication of WO2002032453A1 publication Critical patent/WO2002032453A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • 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
    • A61K39/12—Viral antigens
    • 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
    • A61K39/12—Viral antigens
    • A61K39/187—Hog cholera virus
    • 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
    • A61P31/12—Antivirals
    • 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
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031—Proteins
    • A61K2039/6081—Albumin; Keyhole limpet haemocyanin [KLH]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/24011—Flaviviridae
    • C12N2770/24311—Pestivirus, e.g. bovine viral diarrhea virus
    • C12N2770/24322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/24011—Flaviviridae
    • C12N2770/24311—Pestivirus, e.g. bovine viral diarrhea virus
    • C12N2770/24334—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • the present invention relates to a vaccine prepared by bioengineering technology and a preparation method thereof, and particularly to a swine fever virus vaccine and a preparation method thereof.
  • Swine fever is a malignant infectious disease caused by classical swine fever virus ( ⁇ Classical Swine fever virus, CSFV or Hog Cholera virus, HCV). Once an outbreak, it often causes huge economic losses within a short period of time.
  • CSFV Classical Swine fever virus
  • HCV Hog Cholera virus
  • the swine fever virus subunit vaccine is a swine fever vaccine currently being developed at home and abroad.
  • the vaccine uses genetically-recombined viral envelope proteins to induce immune protection.
  • this vaccine can cope with the mutation of classical swine fever virus to a certain extent, the vaccine contains only one genetic information of the virus. When the virus mutates, the vaccine will lose its effectiveness, and the production cost of the vaccine is still relatively low.
  • the antigenic region sequence of envelope protein E2 of swine fever virus (amino acid residues 690-866) has been shown to induce immune protection, that is, to protect swine fever virus from infection (Vaccine 2000, 18: 2351; Vaccine 1999, 17: 433; J. Virology 1995, 69: 6479; Vaccine 2000, 18: 1374; J. Virology 1993, 67: 5435).
  • the object of the present invention is to provide a synthetic peptide classical swine fever virus vaccine capable of coping with mutations of classical swine fever virus.
  • Another object of the present invention is to provide a method for producing the above-mentioned synthetic peptide swine fever virus vaccine.
  • a synthetic peptide swine fever vaccine comprising at least one of the swine fever virus envelope protein E2 coupled to an IJ carrier protein or carrier polypeptide to form a conjugate.
  • the neutralizing epitope or variant epitope on the swine fever virus envelope protein E2 is located in the antigenic region on the swine fever virus envelope protein E2.
  • the antigenic region is amino acids 690-866 on the swine fever virus-coated phosphin protein E2. Acid residues.
  • neutralizing epitope and variant epitope polypeptides can be selected from the following 14 polypeptide sequences and their variant sequences:
  • the above 14 polypeptides and their conjugates formed by the mutated sequence polypeptide and the carrier can be added to the vaccine.
  • the vaccine should also include acceptable pharmaceutical adjuvants.
  • a method for preparing the above-mentioned synthetic peptide swine fever vaccine basically includes the following steps:
  • Example 1 Preparation of polyclonal swine fever polypeptide (synthetic peptide) based on classical protein of swine fever virus E2 1. Synthesize 11 synthetic peptides (polypeptides) that contain one of the neutralizing epitopes of the antigen region of the classical swine fever virus E2 protein (amino acid residues at positions 690-866). The sequences of these 11 peptides partially overlap each other. 11 The sequence of each polypeptide is:
  • MBS nrmaleimidobenzoyl-N-hydroxy succinimide ester
  • One or more of the above 11 conjugates are respectively formulated with an adjuvant (such as oil adjuvant, etc.) and mixed to prepare a multiple swine fever vaccine.
  • an adjuvant such as oil adjuvant, etc.
  • the fraction ratio of various conjugates can be adjusted according to the probability of variation of each point obtained by statistical processing in different years.
  • Example 2 Preparation of anti-variation-multiple-one swine fever polypeptide based on E2 protein of classical swine fever virus
  • MBS nrmaleimidobenzoyl- N-hydroxy succinimide ester
  • the above 3 conjugates were formulated with Shan adjuvant to prepare a multiple swine fever polypeptide vaccine. Its In the three conjugates, the proportions of the conjugates can be adjusted according to the variation probability of each point obtained by statistical processing in different years.
  • a synthetic peptide containing the neutralizing epitope of the antigenic region of the classical swine fever virus E2 protein the sequence is:
  • the above conjugate is formulated with an oil adjuvant to prepare a swine fever polypeptide vaccine.
  • MBS m-maleimidobenzoyl-hydroxy succinimide ester
  • the present invention utilizes the neutralizing epitope on envelope protein E2 of classical swine fever virus to induce pigs to produce stronger, longer-lasting immune protection characteristics.
  • a multiple vaccine is used to produce pigs.
  • a variety of antibodies to classical swine fever virus that is, when one or several epitopes of classical swine fever virus are mutated, the vaccine-injected pigs are still sufficient to deal with the mutant classical swine fever virus corresponding to other unmutated epitopes Antibodies.
  • the vaccine of the present invention has the following advantages: 1.
  • the vaccine is a highly efficient multiple vaccine that can stimulate the production of a variety of neutralizing antibodies, which can effectively deal with the mutation of the virus, thereby overcoming the shortcomings of the existing swine fever vaccines, which are poor or even ineffective. .
  • the active ingredient of the vaccine is an epitope polypeptide comprising a neutralizing epitope or a variant epitope on envelope protein E2 of swine fever virus coupled to a carrier protein or carrier polypeptide to form a conjugate.
  • epitope polypeptides Does not require attenuated or inactivated pathogens or natural proteins of pathogens, nor does it require genetically engineered protein antigens and pathogen nucleic acids, which can directly induce a predetermined, multiple neutralizing epitope and variant epitope-specific immune response, No genetic material and activity of classical swine fever virus, no side effects induced by genetic material of classical swine fever virus, no danger of reactivation of inactivated or attenuated vaccines, and the use of attenuated classical swine fever vaccine (such as Swine fever rabbit attenuated attenuated vaccine) infection and replication of live swine fever attenuated live virus induced in breeding pigs, sows and pigs, thereby overcoming the potential, current Unknown hazard.
  • attenuated classical swine fever vaccine such as Swine fever rabbit attenuated attenuated vaccine

Abstract

L'invention concerne un vaccin du virus de la peste porcine classique contenant au moins un polypeptide épitope combiné à une protéine porteuse ou un polypeptide porteur formant des conjugués, chacun contenant un épitope de neutralisation ou un polypeptide épitope de mutation se trouvant sur la capsule protéique E2 du virus de la peste porcine classique située dans la région antigénique de ladite capsule protéique, à savoir les résidus d'acides aminés dont la position va de 690 à 866. Le procédé de préparation du vaccin de cette invention consiste à 1) synthétiser de manière artificielle des polypeptides contenant un épitope de neutralisation de la région antigénique ; 2) combiner le polypeptide au vecteur afin de former des conjugués distincts ; 3) formuler un vaccin en combinant lesdits conjugués à l'aide d'un adjuvant. Cette invention a le mérite de lutter efficacement contre les mutations du vaccin de la peste porcine classique, d'être rentable tout en ayant une vaste portée sociale.
PCT/CN2001/001188 2000-08-10 2001-07-20 Vaccin de synthese pour la lutte contre le virus de la peste porcine classique et son procede de preparation WO2002032453A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002223384A AU2002223384A1 (en) 2000-08-10 2001-07-20 Synthetic peptide hog cholera vaccine and method producing it

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN00121291.5 2000-08-10
CN00121291A CN1338309A (zh) 2000-08-10 2000-08-10 一种合成肽猪瘟疫苗及其制备方法

Publications (1)

Publication Number Publication Date
WO2002032453A1 true WO2002032453A1 (fr) 2002-04-25

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CN (1) CN1338309A (fr)
AU (1) AU2002223384A1 (fr)
WO (1) WO2002032453A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007098717A2 (fr) 2006-02-28 2007-09-07 Centro De Ingeniería Genética Y Biotecnología Antigènes vaccinaux chimères utilisés contre le virus de la peste porcine classique
CN110652583A (zh) * 2018-06-29 2020-01-07 西北民族大学 猪口蹄疫二价灭活抗原与猪瘟弱毒株二联苗

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101152570B (zh) * 2007-10-19 2010-11-24 清华大学 一种猪瘟病毒表位疫苗及其制备方法
CN101144818B (zh) * 2007-10-19 2011-04-27 清华大学 检测猪瘟病毒特异性抗体的方法及其酶联免疫试剂盒
CN102485749B (zh) * 2009-10-09 2014-06-04 中牧实业股份有限公司 猪瘟合成肽疫苗及其制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0236977A2 (fr) * 1986-03-07 1987-09-16 Biotechnology Research Partners, Ltd. Vaccins contre la diarrhée bovine virale et le choléra porcin
EP0389034A1 (fr) * 1989-03-19 1990-09-26 Akzo Nobel N.V. Vaccin et test de diagnostic pour le virus du choléra porcin
WO1995035380A1 (fr) * 1994-06-17 1995-12-28 Instituut Voor Dierhouderij En Diergezondheid Sequences nucleotidiques de souches de pestivirus, polypeptides codes par ces sequences, et leur application au diagnostic et a la prevention des infections par pestivirus
WO1996019498A2 (fr) * 1994-12-20 1996-06-27 Akzo Nobel N.V. Proteine de virus de la peste stimulant les cellules t
EP0982402A1 (fr) * 1998-08-14 2000-03-01 Stichting Instituut voor Dierhouderij en Diergezondheid (ID-DLO) Vaccination contre les Pestivirus

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0236977A2 (fr) * 1986-03-07 1987-09-16 Biotechnology Research Partners, Ltd. Vaccins contre la diarrhée bovine virale et le choléra porcin
EP0389034A1 (fr) * 1989-03-19 1990-09-26 Akzo Nobel N.V. Vaccin et test de diagnostic pour le virus du choléra porcin
WO1995035380A1 (fr) * 1994-06-17 1995-12-28 Instituut Voor Dierhouderij En Diergezondheid Sequences nucleotidiques de souches de pestivirus, polypeptides codes par ces sequences, et leur application au diagnostic et a la prevention des infections par pestivirus
WO1996019498A2 (fr) * 1994-12-20 1996-06-27 Akzo Nobel N.V. Proteine de virus de la peste stimulant les cellules t
EP0982402A1 (fr) * 1998-08-14 2000-03-01 Stichting Instituut voor Dierhouderij en Diergezondheid (ID-DLO) Vaccination contre les Pestivirus

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MOORMANN R.J. ET AL., VIROLOGY, vol. 177, no. 1, July 1990 (1990-07-01), pages 184 - 198 *
VAN RIJN P.A. ET AL., VIROLOGY, vol. 237, no. 2, 27 October 1997 (1997-10-27), pages 337 - 348 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007098717A2 (fr) 2006-02-28 2007-09-07 Centro De Ingeniería Genética Y Biotecnología Antigènes vaccinaux chimères utilisés contre le virus de la peste porcine classique
CN110652583A (zh) * 2018-06-29 2020-01-07 西北民族大学 猪口蹄疫二价灭活抗原与猪瘟弱毒株二联苗

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Publication number Publication date
CN1338309A (zh) 2002-03-06
AU2002223384A1 (en) 2002-04-29

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