WO2001009290A2 - Serotype du virus de bronchite infectieuse aviaire - Google Patents

Serotype du virus de bronchite infectieuse aviaire Download PDF

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Publication number
WO2001009290A2
WO2001009290A2 PCT/MX2000/000031 MX0000031W WO0109290A2 WO 2001009290 A2 WO2001009290 A2 WO 2001009290A2 MX 0000031 W MX0000031 W MX 0000031W WO 0109290 A2 WO0109290 A2 WO 0109290A2
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Prior art keywords
infectious bronchitis
avian infectious
further characterized
virus
serotype
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PCT/MX2000/000031
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English (en)
Spanish (es)
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WO2001009290A3 (fr
Inventor
Bernardo Lozano Dubernard
Manuel Joaquin Gay Gutierrez
David Sarfati Misrahi
Ernesto Soto Priante
Jesús Alejandro SUAREZ MARTINEZ
María Eugenia ARANDA MERLO
Jorge Alberto Escamilla Juarez
Mirna Margarita Hernandez Rodriguez
Juan Garcia Garcia
Original Assignee
Laboratorio Avi-Mex, S.A. De C.V.
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Priority claimed from MXPA/A/1999/007146A external-priority patent/MXPA99007146A/xx
Application filed by Laboratorio Avi-Mex, S.A. De C.V. filed Critical Laboratorio Avi-Mex, S.A. De C.V.
Publication of WO2001009290A2 publication Critical patent/WO2001009290A2/fr
Publication of WO2001009290A3 publication Critical patent/WO2001009290A3/fr

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    • 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
    • A61K39/215—Coronaviridae, e.g. avian infectious bronchitis virus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
    • C07K16/1002—Coronaviridae
    • 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
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • 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
    • A61K2039/525—Virus
    • A61K2039/5254—Virus avirulent or attenuated
    • 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
    • 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
    • C12N2770/20011—Coronaviridae
    • C12N2770/20021—Viruses as such, e.g. new isolates, mutants or their genomic sequences
    • 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
    • C12N2770/20011—Coronaviridae
    • C12N2770/20022—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
    • C12N2770/20011—Coronaviridae
    • C12N2770/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • 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
    • C12N2770/20011—Coronaviridae
    • C12N2770/20061—Methods of inactivation or attenuation
    • C12N2770/20064—Methods of inactivation or attenuation by serial passage

Definitions

  • the present invention is related to the techniques for the detection, prevention and treatment of avian infectious bronchitis, and more particularly it is related to a serotype of the avian infectious bronchitis virus.
  • Avian infectious bronchitis is a disease of viral etiology that affects birds and is characterized by high morbidity and low mortality in them.
  • Avian infectious bronchitis is caused by viruses of the Coronavir ⁇ dae family, of which different serotypes and variants that affect the respiratory, reproductive and urinary apparatus of birds have been recognized to a lesser or greater degree, although they also affect other animal species and to the man.
  • Some references that confirm the above are the article "Structure of the infectious bronchitis virus” by Avellaneda, G. E., published in the journal Avicultura Profesional, Vol. 10, No. 1 in 1992; the article “Infectious Bronchitis: Danger for layers", by Butcher, G., et. al., published in the Poultry Industry magazine in January 1992; the book “Poultry diseases” by Calnek, B.W., et.
  • This disease has a great economic impact in the poultry industry, since it considerably decreases the productive parameters of poultry farms, regardless of the zootechnical purpose.
  • chicken fattening causes respiratory signs with high morbidity, decrease in food conversion and food consumption in birds. Additionally, when these viruses are in combination with other pathogens, high mortality can be observed.
  • some strains of the infectious bronchitis virus produce atresia of the oviduct, which once sexual maturity is reached, it is observed as impaction, salpingitis and purulent metritis.
  • Virions can be pleomorphic but generally rounded between 80 and 120 nanometers in diameter, have a crown-shaped lipoprotein shell and the viral genome consists of a non-segmented ribonucleic acid (RNA) chain with a positive sense.
  • the virus has 3 structural proteins: the Protein N of the nucleocapsid, the Giucoprotein M of the membrane and the S that forms the spicules of the surface of the virus. Protein N is relatively more stable than external proteins, which may differ by mutation in the amino acid sequence, which gives rise to different serotypes or antigenic variants of the avian infectious bronchitis virus.
  • the electron microscope is shaped like a cone and consists of two fractions: a first fraction S1 and a second fraction S2.
  • the first and second fractions S1 and S2 contain, respectively, 520 and 625 amino acids.
  • the first fraction S1 is the most external, and constitutes the thick part of the cone, while the second S2 fraction is the thinnest part of the cone and allows the fixation of the S1 fraction to the virus membrane.
  • the S1 protein is responsible for adhesion of the virus to receptors of susceptible cells, and therefore, is essential for virus replication. Additionally, this protein is of great importance, since it contains the antigenic determinants that induce the formation of neutralizing antibodies, in addition to determining the specificity of the serotype or variant.
  • the great diversity of serotypes and variants of the avian infectious bronchitis virus is given by the relative ease of mutation thereof, mainly at the level of the S1 protein that contains the immunogenicity characteristics of the virus, which are specific and can prevent the vaccines are not effective in attacking it when it is a different serotype or a variant not included in them.
  • polyvalent vaccines may contain non-existent serotypes in the farm or geographical area in question, which instead of protecting the birds, can cause an outbreak of the disease when natural passes occur. of the virus in the chicken. Additionally, these vaccines increase the probability of promoting genetic recombinations leading to the appearance of new serotypes or variant strains, which in addition to not being neutralized by the immunity conferred by conventional vaccines, may be more virulent and cause more serious diseases in the birds.
  • an object of the present invention to provide an avian infectious bronchitis virus serotype that allows controlling a type of avian infectious bronchitis that cannot be controlled through the use of the products or methods obtained from from the serotypes known so far. It is another object of the present invention to provide products such as vaccines, diagnostic kits, antibodies, antigens, hybridomas, proteins with specific amino acid sequences, among others, from the avian infectious bronchitis virus serotype of the present invention to make possible prevention, diagnosis and treatment of infectious avian bronchitis.
  • Figure 1 is a comparative diagram showing a phylogenetic analysis of the nucleotide sequence SEQ ID NO: 2, with respect to the nucleotide sequences encoding to obtain the amino acid sequence of the S1 portion of the S protein of various serotypes and variants of the avian infectious bronchitis virus, where the percentages of similarity of the sequences of the various serotypes are indicated.
  • the present invention relates first to a hitherto unknown serotype of the avian infectious bronchitis virus, which for the purposes of the present invention is called BL-56, according to the deposit made in the CollectionInstitut de cultures de mocroorganismes (CNCM ) of the Pasteur Institute, in France, on June 18, 1999, with Deposit Number I-2240, from which an attenuated strain of it is derived, as well as active, inactivated or third generation vaccines, alone or in combination , made using the BL-56, or some product derived from it.
  • CNCM CollectionInstitut de cultures de mocroorganismes
  • Another aspect of the invention relates to the use of BL-56, alone or in combination with other known serotypes, for vaccine production, as well as the BL-56 response of specific antibodies, which react with BL-56 and the manufacture of diagnostic kits for avian infectious bronchitis in which monoclonal and polyclonal antibodies are used. Also part of the invention are the means for the production of the aforementioned products and the methods applicable to the poultry industry for protection against infectious bronchitis through the use of products obtained from BL-56.
  • BL-56 is an encapsulated virus of the Coronaviridae family, which contain single-stranded RNAs, with helical geometry. Virions are pleomorphic and have a diameter from about 80 to 120 nm. However, it has been surprisingly found that BL-56 causes super-infection in vaccinated chickens.
  • the avian infectious bronchitis virus serotype BL-56 was isolated from chickens, and from it, a strain of avian infectious bronchitis virus was obtained, which is significantly neutralized specifically by the antiserum against BL- 56, prepared by inoculation of the same virus in specific pathogen-free (LPE) chickens.
  • LPE pathogen-free
  • Inocula in proportion 1:10 were made in an added nutrient broth of 1000 Ul / ml of penicillin and 20 mg / ml of streptomycin sulfate from lung, trachea and kidney samples from birds with characteristic respiratory clinical signs of bronchitis Avian infectious that could not be prevented by known methods.
  • amino acid sequence SEQ ID NO: 1 corresponding to the S1 portion of the S-protein of the BL-56 avian infectious bronchitis virus of the present invention.
  • nucleotide sequence SEQ ID NO: 2 annexed to the present description corresponds to the nucleotide sequence encoding to obtain the amino acid sequence SEQ ID NO: 1.
  • strain BL-56 was isolated from broilers that suffered a second outbreak of infectious bronchitis, requiring more than 28 passes in chicken embryo to obtain a stable isolation of the virus, that is, to ensure that the virus it will cause in chicken embryos the characteristic lesions of avian infectious bronchitis in 100% of infected polio.
  • the attenuated BL-56 virus strain it is obtained by passing the BL-56 in a suitable culture or medium a sufficient number of times to reduce its pathogenicity without losing its immunogenicity.
  • the attenuated strain of BL-56 is obtained by passing BL-56 into chicken embryos, preferably by inoculation in a location selected between allantoic cavity; chorioallantoid membrane; yolk sac; amniotic cavity; and, the embryo itself, at least 51 times.
  • the passes are preferably made at regular intervals of 48 to 72. In a specific modality, the passes are made between 36 hours and 48 hours of virus culture. , preferably every 48 hours. In an additional modality of the BL-56 attenuated virus, the passes for obtaining it are made in avian cell cultures, preferably in kidney cells of chicken embryo.
  • the virus is grown, preferably in an LPE chicken embryo, while for the preparation of an inactive vaccine, the BL-56 virus after harvest, it is inactivated by the use of an inactivating agent, preferably selected from formaldehyde and ⁇ -propiolactone, after which the pH is adjusted to physiological pH and the inactivating agent is neutralized.
  • an inactivating agent preferably selected from formaldehyde and ⁇ -propiolactone
  • the adjuvant agent is selected from N-Z amines; hydrolyzed peptones; mannitol; albumins; lactose; phosphated solutions; skimmed casein; amino acids; hydrolyzed gelatins; or, mixtures thereof, subsequently lyophilizing.
  • the adjuvant agent is selected from emulsions of the water type in mineral oil or in vegetable oil, or mixtures thereof in the presence of the emulsifying agent, which in turn, it is selected from emulsifying agents with a hydrophilic-lipophilic balance (HLB) between 6 and 8, preferably selected from non-ionic compounds; derivatives of an alkylene oxide; derivatives of a tetrahydric alcohol; and / or esters or fatty acid esters of the type that includes between 10 and 20 carbon atoms.
  • HLB hydrophilic-lipophilic balance
  • sorbitan polyoxyethylene monooleate (commercially known as Tween 80) is used; sorbitan monooleate (commercially known as Span 80); ma ⁇ osa monooleate (commercially known as Arlacel 80 and Arlacel A); or mixtures thereof.
  • a water: oil ratio is used on the scale of 1: 1 to 3: 7, approximately. Preferably a ratio of approximately 7:13 is used.
  • the preferred embodiment of the method for prevention and control of avian infectious bronchitis of the present invention is to deliver the active BL- vaccine. 56 to the birds preferably by drop in the eye, drop in the nose, in the drinking water, or by aerosol.
  • the use of the vaccine is done by providing it from one day of age until the posture is broken, that is, around 18 weeks.
  • Prevention of infectious avian bronchitis is achieved using preferably from 10 3 to 10 7 DIEP 5 or% per bird, approximately.
  • the active infectious bronchitis vaccine obtained from BL-56 is used in combination with other active avian vaccines, preferably selected from vaccines against Newcastle disease virus, Marek disease virus, Fabrizio pouch infection, reovirus, avian encephalomyelitis virus, chicken anemia agent; and / or other serotypes of avian infectious bronchitis.
  • active avian vaccines preferably selected from vaccines against Newcastle disease virus, Marek disease virus, Fabrizio pouch infection, reovirus, avian encephalomyelitis virus, chicken anemia agent; and / or other serotypes of avian infectious bronchitis.
  • a further embodiment of the method for prevention and control of avian infectious bronchitis of the present invention is to provide the inactivated vaccine to the birds, preferably subcutaneously or intramuscularly from approximately 10 to 20 weeks of age.
  • the prevention of avian infectious bronchitis is carried out by providing an inactivated BL-56 vaccine containing an antigenic equivalent from 10 5 to 10 8 DIEPsoo, per bird, approximately. Preferably it is achieved using between 10 ⁇ and 10 7 DIEP 50 % per bird.
  • the BL-56 inactivated vaccine is supplied in combination with other inactivated avian vaccines, preferably selected from vaccines against Newcastle disease virus, low posture syndrome virus; and / or other serotypes of avian infectious bronchitis.
  • other inactivated avian vaccines preferably selected from vaccines against Newcastle disease virus, low posture syndrome virus; and / or other serotypes of avian infectious bronchitis.
  • Such products may be, but are not limited to hybridomas characterized in that they produce antibodies specific to BL-56; monoclonal and polyclonal antibodies specific for BL-56; sera obtained from inoculation of BL-56 in chicken embryos; antigens characterized in that they generate antibodies against BL-56, the S1 portion of protein S of serotype BL-56; nucleotide sequences that generate the S1 portion of the S protein of the BL-56 serotype; and / or, diagnostic kits containing antibodies and / or antigens from BL-56.
  • hybridomas characterized in that they produce antibodies specific to BL-56; monoclonal and polyclonal antibodies specific for BL-56; sera obtained from inoculation of BL-56 in chicken embryos; antigens characterized in that they generate antibodies against BL-56, the S1 portion of protein S of serotype BL-56; nucleotide sequences that generate the S1 portion of the S protein of the BL-56 serotype
  • an active vaccine was obtained by 51 aces of BL-56 in LPE chicken embryo, and was formulated using skimmed casein, sucrose and phosphates as an adjuvant.
  • the production of a batch of broiler chicken that was in a region affected by avian infectious bronchitis was divided into 2 sections, SE1 and SE2.
  • a commercial vaccine against infectious bronchitis, useful for combating the Massachusetts serotype, was applied to the chickens of section SE1, while the vaccine obtained in the manner described above from BL-56 was applied to section SE2.
  • the BL-56 avian infectious bronchitis virus serotype of the present invention is different from the avian infectious bronchitis serotypes known so far, and will be apparent to any person skilled in the art who the modalities of the products obtained therefrom, and of the methods of application of said products described above, are only illustrative but not limiting of the present invention, since numerous changes of consideration in their details are possible without departing from the scope of the invention.

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Abstract

L'invention concerne un sérotype du virus de bronchite infectieuse aviaire, permettant de contrôler un type de bronchite infectieuse aviaire ne pouvant pas être contrôlé par les produits ou les méthodes connus jusqu'à présent. A partir du nouveau sérotype, il est possible d'obtenir des produits, tels que des vaccins, des kits de diagnostic, des anticorps, des antigènes, des hybridomes, des protéines avec des séquences d'amino-acides spécifiques, entre autres, permettant de prévenir, de diagnostiquer et de traiter la bronchite infectieuse aviaire.
PCT/MX2000/000031 1999-07-30 2000-07-28 Serotype du virus de bronchite infectieuse aviaire WO2001009290A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
MX997146 1999-07-30
MXPA/A/1999/007146A MXPA99007146A (en) 1999-07-30 Avian infectious bronchitis virus serotype

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WO2001009290A2 true WO2001009290A2 (fr) 2001-02-08
WO2001009290A3 WO2001009290A3 (fr) 2001-08-23

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1508615A1 (fr) * 2003-08-18 2005-02-23 Amsterdam Institute of Viral Genomics B.V. Acides nucléiques, protéine, procédé de production des vaccins, médicaments et agents diagnostiques du coronavirus
WO2005017133A1 (fr) * 2003-08-18 2005-02-24 Amsterdam Institute Of Viral Genomics B.V. Coronavirus, acide nucleique, proteine, et methodes servant a generer un vaccin, medicaments et diagnostiques
EP1553169A1 (fr) * 2004-01-07 2005-07-13 Amsterdam Institute of Viral Genomics B.V. d'Acides nucléiques, protéine, procédé de production des vaccines, medicaments et agents diagnostiques du coronavirus
CN103599531A (zh) * 2013-09-23 2014-02-26 天津瑞普生物技术股份有限公司 一种鸡传染性支气管炎活疫苗、耐热保护剂及其制备方法
CN104130981A (zh) * 2014-07-10 2014-11-05 中国农业科学院哈尔滨兽医研究所 鸡传染性支气管炎病毒疫苗株及其在制备灭活疫苗中的应用
CN105802918A (zh) * 2014-12-29 2016-07-27 普莱柯生物工程股份有限公司 鸡肾型传染性支气管炎病毒毒株及其疫苗组合物、制备方法和应用
CN116836939A (zh) * 2023-07-05 2023-10-03 中国兽医药品监察所 一种抗禽脑脊髓炎病毒单克隆抗体杂交瘤细胞株、单克隆抗体、试剂或试剂盒及其应用
US11999766B2 (en) 2019-05-10 2024-06-04 Boehringer Ingelheim Vetmedia Gmbh Modified S1 subunit of the coronavirus spike protein

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EP0186368A2 (fr) * 1984-12-11 1986-07-02 Pitman-Moore, Inc. Préparations biologiques
US4867975A (en) * 1988-01-27 1989-09-19 University Of Delaware Live attenuated temperature-sensitive avian infectious bronchitis virus vaccines and preparation and use thereof
WO1993023421A1 (fr) * 1992-05-08 1993-11-25 Smithkline Beecham Corporation Vaccin universel contre le coronavirus

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Title
HYUK MOO KWON ET AL: "Molecular cloning and sequence comparison of the S1 glycoprotein of the gray and JMK strains of avian infectious bronchitis virus" VIRUS GENES, vol. 99, num. 3, 1995, páginas 2119-229, XP002901529 *

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8835107B2 (en) 2003-08-18 2014-09-16 Amsterdam Institute Of Viral Genomics B.V. Coronavirus, nucleic acid, protein, and methods for the generation of vaccine, medicaments and diagnostics
WO2005017133A1 (fr) * 2003-08-18 2005-02-24 Amsterdam Institute Of Viral Genomics B.V. Coronavirus, acide nucleique, proteine, et methodes servant a generer un vaccin, medicaments et diagnostiques
EP1526175A2 (fr) 2003-08-18 2005-04-27 Amsterdam Institute of Viral Genomics B.V. Acides nucléiques, protéine, procédé de production des vaccins, médicaments et agents diagnostiques du coronavirus
EP1526175A3 (fr) * 2003-08-18 2005-05-04 Amsterdam Institute of Viral Genomics B.V. Acides nucléiques, protéine, procédé de production des vaccins, médicaments et agents diagnostiques du coronavirus
EP1508615A1 (fr) * 2003-08-18 2005-02-23 Amsterdam Institute of Viral Genomics B.V. Acides nucléiques, protéine, procédé de production des vaccins, médicaments et agents diagnostiques du coronavirus
CN1867667A (zh) * 2003-08-18 2006-11-22 阿姆斯特丹病毒基因组学研究院股份有限公司 冠状病毒、核酸、蛋白质及用于产生疫苗、药物和诊断剂的方法
US7803918B2 (en) 2003-08-18 2010-09-28 Amsterdam Institute Of Viral Genomics B.V. Coronavirus, nucleic acid, protein, and methods for the generation of vaccine, medicaments and diagnostics
EP1526175B2 (fr) † 2003-08-18 2021-04-14 Amsterdam Institute of Viral Genomics B.V. Acides nucléiques, protéine, procédé de production des vaccins, médicaments et agents diagnostiques du coronavirus
CN1867667B (zh) * 2003-08-18 2014-06-04 阿姆斯特丹病毒基因组学研究院股份有限公司 冠状病毒、核酸、蛋白质及用于产生疫苗、药物和诊断剂的方法
EP1553169A1 (fr) * 2004-01-07 2005-07-13 Amsterdam Institute of Viral Genomics B.V. d'Acides nucléiques, protéine, procédé de production des vaccines, medicaments et agents diagnostiques du coronavirus
CN103599531A (zh) * 2013-09-23 2014-02-26 天津瑞普生物技术股份有限公司 一种鸡传染性支气管炎活疫苗、耐热保护剂及其制备方法
CN104130981A (zh) * 2014-07-10 2014-11-05 中国农业科学院哈尔滨兽医研究所 鸡传染性支气管炎病毒疫苗株及其在制备灭活疫苗中的应用
CN105802918A (zh) * 2014-12-29 2016-07-27 普莱柯生物工程股份有限公司 鸡肾型传染性支气管炎病毒毒株及其疫苗组合物、制备方法和应用
CN105802918B (zh) * 2014-12-29 2019-11-19 普莱柯生物工程股份有限公司 鸡肾型传染性支气管炎病毒毒株及其疫苗组合物、制备方法和应用
US11999766B2 (en) 2019-05-10 2024-06-04 Boehringer Ingelheim Vetmedia Gmbh Modified S1 subunit of the coronavirus spike protein
CN116836939A (zh) * 2023-07-05 2023-10-03 中国兽医药品监察所 一种抗禽脑脊髓炎病毒单克隆抗体杂交瘤细胞株、单克隆抗体、试剂或试剂盒及其应用
CN116836939B (zh) * 2023-07-05 2024-01-26 中国兽医药品监察所 一种抗禽脑脊髓炎病毒单克隆抗体杂交瘤细胞株、单克隆抗体、试剂或试剂盒及其应用

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