USRE32283E - Vaccines - Google Patents
Vaccines Download PDFInfo
- Publication number
- USRE32283E USRE32283E US06/682,859 US68285984A USRE32283E US RE32283 E USRE32283 E US RE32283E US 68285984 A US68285984 A US 68285984A US RE32283 E USRE32283 E US RE32283E
- Authority
- US
- United States
- Prior art keywords
- virus
- ibv
- vaccine
- vaccines
- derived
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
Links
- 229960005486 vaccine Drugs 0.000 title claims abstract description 65
- 241000700605 Viruses Species 0.000 claims abstract description 151
- 241000711450 Infectious bronchitis virus Species 0.000 claims abstract description 37
- 208000015181 infectious disease Diseases 0.000 claims abstract description 29
- 230000002458 infectious effect Effects 0.000 claims abstract description 22
- 206010006451 bronchitis Diseases 0.000 claims abstract description 21
- 244000144977 poultry Species 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 15
- 244000005700 microbiome Species 0.000 claims abstract description 3
- 239000012071 phase Substances 0.000 claims description 10
- 239000008346 aqueous phase Substances 0.000 claims description 4
- 229940031551 inactivated vaccine Drugs 0.000 claims description 4
- 210000000605 viral structure Anatomy 0.000 claims description 4
- 239000003995 emulsifying agent Substances 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- 239000002480 mineral oil Substances 0.000 claims description 2
- 239000007762 w/o emulsion Substances 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 235000010446 mineral oil Nutrition 0.000 claims 1
- 239000004094 surface-active agent Substances 0.000 claims 1
- 235000015112 vegetable and seed oil Nutrition 0.000 claims 1
- 239000008158 vegetable oil Substances 0.000 claims 1
- 238000004108 freeze drying Methods 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 5
- 238000002255 vaccination Methods 0.000 abstract description 5
- 241000287828 Gallus gallus Species 0.000 description 25
- 235000013330 chicken meat Nutrition 0.000 description 22
- 235000013601 eggs Nutrition 0.000 description 18
- 238000012360 testing method Methods 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 15
- 239000000463 material Substances 0.000 description 14
- 239000000725 suspension Substances 0.000 description 13
- 235000013594 poultry meat Nutrition 0.000 description 11
- 241000271566 Aves Species 0.000 description 9
- 239000012530 fluid Substances 0.000 description 9
- 238000006386 neutralization reaction Methods 0.000 description 9
- 238000011534 incubation Methods 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 210000002257 embryonic structure Anatomy 0.000 description 7
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 230000002163 immunogen Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 241000831652 Salinivibrio sharmensis Species 0.000 description 4
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 4
- 238000004945 emulsification Methods 0.000 description 4
- 230000002779 inactivation Effects 0.000 description 4
- 206010011409 Cross infection Diseases 0.000 description 3
- 206010029803 Nosocomial infection Diseases 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- FCPVYOBCFFNJFS-LQDWTQKMSA-M benzylpenicillin sodium Chemical compound [Na+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1 FCPVYOBCFFNJFS-LQDWTQKMSA-M 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 238000012792 lyophilization process Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 210000003437 trachea Anatomy 0.000 description 3
- 239000005723 virus inoculator Substances 0.000 description 3
- JDRAOGVAQOVDEB-KTKRTIGZSA-N (3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl) (z)-octadec-9-enoate Chemical compound OC1COC2C(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC21 JDRAOGVAQOVDEB-KTKRTIGZSA-N 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241000711573 Coronaviridae Species 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- LUXUAZKGQZPOBZ-SAXJAHGMSA-N [(3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (Z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O LUXUAZKGQZPOBZ-SAXJAHGMSA-N 0.000 description 2
- 210000001691 amnion Anatomy 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- VEZXCJBBBCKRPI-UHFFFAOYSA-N beta-propiolactone Chemical compound O=C1CCO1 VEZXCJBBBCKRPI-UHFFFAOYSA-N 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 210000003292 kidney cell Anatomy 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 210000003101 oviduct Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000007918 pathogenicity Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 229960000380 propiolactone Drugs 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- 241000711404 Avian avulavirus 1 Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 206010006811 Bursitis Diseases 0.000 description 1
- 241000702263 Reovirus sp. Species 0.000 description 1
- 230000010530 Virus Neutralization Effects 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 230000027645 antigenic variation Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000991 chicken egg Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 229960003255 natamycin Drugs 0.000 description 1
- NCXMLFZGDNKEPB-FFPOYIOWSA-N natamycin Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C[C@@H](C)OC(=O)/C=C/[C@H]2O[C@@H]2C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 NCXMLFZGDNKEPB-FFPOYIOWSA-N 0.000 description 1
- 235000010298 natamycin Nutrition 0.000 description 1
- 239000004311 natamycin Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000010773 plant oil Substances 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012770 revaccination Methods 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5252—Virus 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
- A61K2039/51—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
-
- 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
-
- 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
- A61K2039/70—Multivalent 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
- C12N2770/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- 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
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
- Y10S424/816—Viral vaccine for avian species, e.g. poultry or other birds
Definitions
- infectious bronchitis vaccines for poultry has been known for many years and infectious bronchitis is an important affection of the respiratory system, the kidneys and oviduct of poultry.
- the cause of this syndrome is a corona virus and poultry are severely affected by epizootics of this disease.
- Infectious bronchitis causes a high mortality, especially in young poultry and besides mortality and more or less strong respiratory symptoms, egg production drops occur due to lesions to the oviduct and/or as a result of the stress situation in which the poultry falls after an infection with IB virus.
- infections with IB virus may stimulate latent virus- or bacterial infections and may give rise in this way to severe economical losses, especially in the broiler field.
- viruses having undergone 25 or more embryo passages to reduce their pathogenicity and their disseminating ability have been used up to now, such as viruses derived from the Massachusetts type and more particularly the IBV W 48, M 41 and 82828 strains of this type, besides the Connecticut isolates, e.g. the A 5968 strain.
- the immunizing capacity of these viruses is very specific against either Massachusetts or Connecticut types of IB virus. This is in contrast to the IBV H 52 and H 120 strains which have been passaged approximately 52 and 120 times respectively in embryonated chicken eggs and which have a relatively broad immunizing capacity.
- the H-strain is presently applied on a world wide scale because of its broad immunization spectre against among others Massachusetts and Connecticut types of IB-virus and has been isolated and attenuated by Bijlenga et al as disclosed in Tijdschr. Diergeneesk. 81:43, "Infectious bronchitis in chicks in the Netherlands" (1956), Tijdschr. Diergeneesk. 85:320 (1960), Tijdschr. Diergeneesk. 85:279 (1960) and Tijdschr. Diergeneesischen 85:398 (1960).
- novel IB viruses could surprisingly be obtained and determined, which deviate from the frequently applied IB viruses of the H type (e.g. IB H 120 and IB H 52), but show corresponding antigenic properties with the viruses described in the beforementioned European patent application.
- the frequently used IB viruses of the H-type deviates from new IB virus in cross neutralization tests (virus neutralization tests) according to e.g. the method as described in American Association of Avian Pathologists, "Isolation and Identification of Avian Pathogens", page 184 (1975), in the understanding that antisera diluted in a ratio of 1:5 are used, and in challenge experiments with subsequent virus reisolation tests.
- novel IB virus causes respiratory symptoms with animals showing high antibody titers against the IB H-strain, and with still laying animals, egg production drops.
- Each of the new IB virus generates after inoculation antibodies against not only itself, but also against the IB viruses different from the H-type strains, as mentioned in the above-cited European patent application.
- the new IB viruses therefore show a broad spectrum against the nowadays frequently occuring IB virus strains deviating from the ones which can be combatted with vaccines derived from the H-strain.
- novel infectious virus strains of the invention are novel serotypes of virus strain identified by the internal No. Brabant 802 and is deposited at the Czechoslovak National Collection of Type Cultures of the Institute of Hygiene and Epidemiology in Prague under No. CNCTC 18/82 and deposited at the Collection of Nationale d'Institute Pasteur, Paris under No. I-202 and a virus strain identified by the internal No. Gelderland 901 and is deposited at the Czechoslovak National Collection of Type Cultures of the Institute of Hygiene and Epidemiology in Prague under No. CNCTC AO 17/81 and deposited at the Collection Nationale de Cultures de Microorganismes d'Institute Pastuer, Paris under No. I-168.
- viruses were isolated by means of the trachea swab method from broiler chickens which showed at an age of 4-5 weeks respiratory symptoms after previous vaccination at the age of one day with IB vaccine of the H 120 type, whereby the animals found themselves at the moment of isolation in the district, which was indicated in the hereinbefore used internal notation (Gelderland and Brabant respectively). It was found that by attenuation to SPF-chicken embryos, the isolated virus strains lost their pathogenicity for SPF chickens to a major degree, in spite of the fact that its immunizing ability still remained present.
- the virus reisolation test was carried out 5 days after challenge using trachea swab material and the virus reisolation technique used is described in "Specifications for the production and control of avian live virus vaccines" of the Ministry of Agriculture, Fisheries and Food of the United Kingdom Central Veterinary Laboratory of Biological Products and Standards Department, New Haw, Weybridge, Surrey KT153 NB, 2nd Edition (1977), p. 12.
- FIG. 1 the neutralization indices (vertical axis) determined for the IBV test viruses H. 120, Gelderland. 901, Overijssel. 728, Limburg. 536, Utrecht. 101 and Brabant. 801 respectively and for the homologeous test virus Gelderland. 901, are plotted for the six IBV anti sera types H.52, Gelderland. 901, Overijssel. 728, Limburg. 536, Utrecht. 101 and Brabant.801 on the horizontal axis.
- the novel IB virus strains differs antigenitically in a significant degree from the usually applied H-virus and have common antigenic properties with the viruses of the beforementioned European application.
- the EID 50 content of the cell material and culture medium appeared to reside on comparable levels 2, 4 and 7 days after the inoculation of the virus agent, i.e. the nucleic acid to be replicated belongs to the group of the ribonucleic acid.
- the virus agent present in the amnion allantoic fluid harvested within 30 hours after the artificial infection possessed a diameter of about 100 nm.
- About 15 nm long projections were present on the surface of this virus and the virus has the size and shape of a corona virus to which also the avian bronchitis viruses are regarded to belong.
- novel serotype of the IB-viruses of the present invention make the novel virus strains especially suitable for the preparation of as well inactivated as live poultry vaccines on behalf of a more efficient protection against infectious bronchitis, especially in areas or countries wherein the described deviating serotype of the present application and the above-mentioned European patent application occur besides the IB viruses of the so called H-type.
- virus strains of the serotypes of the hereinbefore mentioned novel virus strains may successfully be used for the preparation of mixed live and inactivated vaccines derived as well from the novel IB strain as from the H-strain.
- novel IB vaccines of the present invention may be derived from the beforementioned novel strains G. 901 and B. 802 and mutants or variants thereof belonging to the same serotype.
- the novel IBV vaccines of the present invention may be obtained by propagation of the novel virus strains by methods known in the art in principle and optionally followed by inactivation by methods known in the art in principle.
- the virus may be propagated in embryonated SPF chicken eggs or in suitable cell cultures such as chicken kidney cell cultures.
- suitable cell cultures such as chicken kidney cell cultures.
- the cultivated virus material is collected and purified and finally one or more stabilizers and, if desired, antibiotics such as sodium penicillin G, streptomycin or natamycin may be added and the mixture is lyophilized.
- the seed virus concerned is inoculated under sterile conditions into the allantoic cavity of 10-11 days preincubated SPF type I chicken eggs. After incubation for 28 to 48 hours at 37° C., the amnion-allantoic fluid of the then still living and of the specifically dead (i.e. between 24 hours after the seed virus inoculation and the end of the incubation period) embryos is harvested, purified and lyophilized after optional addition of stabilizers and/or antibiotics.
- single vaccines can be prepared containing the virus in an amount of at least 10 4 . 0 EID 50 per dose after lyophilization, while e.g. so prepared combined vaccines of one of the novel virus strain and a known H-strain and/or more other IBV-strains showed a virus content of ⁇ 2 ⁇ 10 4 . 0 EID 50 per dose and preferably a content of each of the virus components of at least 10 4 . 0 EID 50 per dose.
- the present invention also relates to novel, inactivated as well as live, IBV vaccines which have been at least derived from one virus belonging to one of the serotypes of the novel IB virus strains G.901 and B.802 and to the use of such vaccines to protect poultry.
- live vaccines derived from viruses of the serotypes of the novel virus G.901 or from the novel virus B.208 alone or from the H-type virus with the novel IB-virus are used. More preferably, live vaccines derived from H 120 or H 52 virus strain from viruses of the serotype of the G.901 virus strain or from the B.802, virus strain are used. The vaccines may also be administered to young chickens.
- novel live virus vaccines may be administered by the so called eyedrop- or nosedrop-, the drinking-water-or spray-methods.
- Vaccination of the novel live vaccines of the invention preferably is carried out with poultry of an age of 1 day to 18 weeks.
- the novel inactivated vaccines may be administered to the birds subcutaneously or intramuscularly and may be used for revaccination purposes only.
- suitable inactivated combination vaccines as indicated hereinbefore may be mentioned those derived from the strains G.901, B.801 and H.52, derived from the strains, B.802, L.536 and H.52, derived from the strains G.901, B.802, B.801 and H.52 respectively. It will be appreciated that also combined live or inactivated vaccines derived from the novel IB strain type G.901 or B.802 and one or more completely other virus types such as e.g. the Newcastle disease virus, adenolike virus, infectious bursitis virus or reo virus, are a feature of the present invention too.
- inactivated IBV vaccines of the invention there may be started from e.g. an amnionallantoic fluid which may be diluted with PBS and to which a suitable carrier is added after inactivation by methods known in the art, e.g. by means of beta-propiolactone or formaline.
- the virus suspension with a suitable virus content is processed to a water-in-oil emulsion vaccine derived from a mineral or plant oil and one of more emulsifiers such as non-ionic surface-active compounds derived from alkylene oxide and/or hexahydric alcohols and/or higher natural fatty acids (C 10 -C 20 ) such as esters or esterethers.
- emulsifiers examples include sorbitan or mannide monooleate (Span 80 ,Arlacel 80 ,Arlacel A ) and polyyoxyethylene (20) sorbitan monooleate (e.g. Tween 80 ).
- the volume ratio between the aqueous phase (virus fluid) and the oily phase may vary from 3:7 to 1:1 and lies preferably at a ratio of about 7:13.
- Type I SPF chicken egg preincubated for 10 to 11 days were inoculated into the allantoic cavity with 10 3 . 0 to 10 4 . 0 EID 50 IBV G.901 seed virus (0.2 ml per egg) and the eggs were candled for the first time 20 to 24 hours after the virus inoculation and all aspecifically dead embryos were removed. After an incubation period of in total 28 hours at +37° C., the amnion-allantoic fluid (AAF) was harvested.
- AAF amnion-allantoic fluid
- the virus material was subsequently stabilized by addition of at least 3% by weight of albumin and/or mannitol and the stabilized bulk virus material was frozen to at least -35° C. and stored at such temperature until the further processing phase.
- EID 50 Error Infectious Dose 50% assay method. After the test results were available, the virus material was thawed and filled into lyophilization flasks. The virus content (volume) was adjusted in such a way that at the end of the subsequent lyophilization there were still at least 10 4 . 0 EID 50 of the concerning virus per dose present in the vaccine. The flasks were sealed under vacuum at the end of the lyophilization process.
- Type I SPF chicken eggs which had been preincubated for 10 to 11 days were inoculated into the allantoic cavity with 10 3 . 0 to 10 4 . 0 EID 50 of H.52 or G.901 seed virus (0.2 ml in total per egg) and the eggs were candled for the first time 20 to 24 hours after the virus inoculation. All aspecifically dead embryos were removed and after an incubation period of a total 32 hours at 37° C., the AAF was harvested.
- samples of this material were tested for their virus content by the EID 50 assay method.
- the virus material was thawed and filled out into lyophilization flasks after the test results were available.
- the virus content (volume) was adjusted in such a way that at the end of the lyophilization process, the vaccine contained per dose at least 10 4 . 0 EID 50 of each virus concerned.
- the flasks were sealed under vacuo at the end of the lyophilization process.
- care had to be taken that the minimum virus content for all virus components was reached.
- Example 2A In a manner similar to Example 2A, the virus was cultivated in SPF eggs and the obtained virus suspension was treated in a similar way as in Example 2B until the frozen phase was reached but without addition of antibiotics and stabilizers.
- the frozen AAF was thawed and inactivated in a water bath by 0.1% of beta-propiolactone for a period of 90 minutes at 37° C. Then, the virus suspension was kept overnight at +4° C. and the inactivation was checked by inoculation of preincubated, embryonated SPF chicken eggs with the inactivated virus material and subsequent incubation.
- the AAF's of strain H.52 and of strains G.901 were mixed in a ratio of 3:2 and the mixed inactivated AAF was diluted, if necessary, with PBS+0.3% of formaline depending on the virus content of each virus type determined in the noninactivated AAF (to a concentration of at least 10 7 . 0 EID 50 per ml for all virus strains). 3.5% of Tween 80 were added to the virus suspension of the two strains and the inactivated virus suspension was mixed with an oil phase in the ratio of 6.5 parts of oil to 3.5 parts of virus fluid and emulsified so that the average particle size of the aqueous phase was about 0.5 ⁇ .
- the emulsification was carried out with an Ultra Turrax homogenizer or by passing the starting mixture through a colloid mill.
- the oil phase had the following composition: Marcol 5 2 (white paraffinic Esso oil) 93.5% Arlacel A ,Arlacel 80 or Span 80 (mannide monooleate) 6.5%.
- the components of the oil phase were separately heated to 110° C. in an autoclave or the mixture was sterilized by filtration.
- the B.801 virus and the G.901 virus were cultivated in SPF eggs in the same way as described in Example 1 for the G.901 virus strain and H.52 virus containing AAF was prepared in the same way as in Example 2.
- the treatment of the virus suspensions of the three strains was carried out according to the corresponding steps of Example 3 until the inactivated AAF's were mixed.
- the inactivated AAF of strain H.52 was then mixed with the AAF of strain G.901 and of strain B.801 in the ratio of 8:3:3.
- the mixed inactivated AAF was diluted, if necessary, with PBS+0.3% of formaline depending on the virus conent of each virus type determined in the non-inactivated AAF (at least 10 7 .
- EID 50 per ml for all virus strains 2.6% of Tween 80 were added to the virus suspension of the three strains and the inactivated virus suspension was mixed with an oil phase in the ratio of 6.0 parts of oil to 4.0 parts of virus fluid and emulsified so that the average particle size of the aqueous phase was about 0.5 ⁇ .
- the emulsification was carried out with an Ultra Turrax homogenizer or by passing the starting mixture throught a colloid mill.
- the composition of the oil phase was the same as in Example 3.
- Cultivation of virus and treatment of the virus suspension was carried out according to the corresponding steps of Example 1, but AAF was harvested after an incubation period of 32 hours at 37° C. instead of 28 hours.
- the B.802 virus and L.536 virus were cultivated in SPF eggs in the same way as described in Example 1 for the G.901 virus, but an incubation period of 32 hours was taken before AAF was harvested.
- H.52 virus was cultivated in the same way as in Example 2 and the treatment of virus suspensions of the three strains was carried out according to the corresponding steps in Example 4.
- the inactivated AAF's of strain H.52, strain B. 802 and strain L.356 were mixed in the ratio 3:1:1 and further treatment and emulsification was carried out as described in Example 4.
- the B.802 virus and G.901 virus were cultivated in SPF eggs in the same way as described in Example 1 for the G.901 virus, but an incubation period of 32 hours was taken before AAF was harvested and H.52 virus was cultivated in the same way as in Example 2.
- the treatment of the virus suspensions of the three strains was carried out according to the corresponding steps in Example 4 and the inactivated AAF's of strain H.52, strain B.802 and strain G.901 were mixed in the ratio 3:1:1. Further treatment and emulsification was carried out as described in Example 4.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Pulmonology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Infectious bronchitis vaccines for poultry derived from at least a virus strain of a novel serotype of the infectious-bronchitis virus (IBV), identified by the internal indication Gelderland. 901 and Brabant. 802, which have been deposited at the Czechoslovak National Collection of Type Cultures of the Institute of Hygiene and Epidemiology under the numbers CNCTC AO 17/81 and CNCTC AO 18/82 and at the Collection Nationale de Cultures de Microorganismes d'Institut Pasteur, under Nos. I-168 and I-202 and combined infectious-bronchitis vaccines derived from the IBV H. 120 or the IBV H. 52 of the Massachusetts type strain together with the novel before-mentioned virus strain; the infectious-bronchitis virus strain itself, and a process for preventing infectious-bronchitis in poultry by vaccination with a vaccine derived from the before-mentioned strains. Preferably, live infectious bronchitis vaccines are prepared, which contain a virus content of at least 104.0 EID50 per dosage of each of the virus strains after freeze drying.
Description
The use of live infectious bronchitis vaccines for poultry has been known for many years and infectious bronchitis is an important affection of the respiratory system, the kidneys and oviduct of poultry. The cause of this syndrome is a corona virus and poultry are severely affected by epizootics of this disease. Infectious bronchitis causes a high mortality, especially in young poultry and besides mortality and more or less strong respiratory symptoms, egg production drops occur due to lesions to the oviduct and/or as a result of the stress situation in which the poultry falls after an infection with IB virus. Moreover, infections with IB virus may stimulate latent virus- or bacterial infections and may give rise in this way to severe economical losses, especially in the broiler field.
To combat infectious bronchitis vaccines derived from inactivated virus as well as those derived from live virus are used. However, it was found that in some cases a loss of immunogenic properties occured after inactivation of these viruses with e.g. formaline and ultra violet light (M. S. Hofstad, Diseases of Poultry, Biester and Schwarte, Iowa University, Press. Ames. (1965), 615). As sound chickens can be killed or diseased by primary vaccination with live, non or slightly attenuated virus vaccines, whereby an especial danger exists for animals of less than 2 or 3 weeks old or for chickens shortly before the start or during laying. People skilled in this art have a clear preference for the application of dead vaccines which still have sufficient immunogenic properties, or of live vaccines which was tried to increase the harmlessness of such vaccines by means of attenuation of the original IB field virus isolates.
For such modified live virus vaccines, viruses having undergone 25 or more embryo passages to reduce their pathogenicity and their disseminating ability have been used up to now, such as viruses derived from the Massachusetts type and more particularly the IBV W 48, M 41 and 82828 strains of this type, besides the Connecticut isolates, e.g. the A 5968 strain. The immunizing capacity of these viruses is very specific against either Massachusetts or Connecticut types of IB virus. This is in contrast to the IBV H 52 and H 120 strains which have been passaged approximately 52 and 120 times respectively in embryonated chicken eggs and which have a relatively broad immunizing capacity. The H-strain is presently applied on a world wide scale because of its broad immunization spectre against among others Massachusetts and Connecticut types of IB-virus and has been isolated and attenuated by Bijlenga et al as disclosed in Tijdschr. Diergeneesk. 81:43, "Infectious bronchitis in chicks in the Netherlands" (1956), Tijdschr. Diergeneesk. 85:320 (1960), Tijdschr. Diergeneesk. 85:279 (1960) and Tijdschr. Diergeneeskunde 85:398 (1960).
Although the use of most vaccines of these modified strains has appeared to be fairly safe and effective up to now, these vaccines appear to be more and more unable to prevent outbreaks of infectious bronchitis in a sufficient manner under certain conditions as discussed in Avian Diseases, Vol. 20, No. 1, pages 42 and 177 (1976) and Avian Diseases, Vol. 19, No. 2, pages 323 and 583 (1975). This shortcoming of the present IB vaccines is attributed to occurring antigenic variations of the virus in an important degree, as appears e.g. from Archiv fur die Gesamte Virusforschung 34, p. 32 (1971) and Cunningham C. H. Develop. Biol. Standard, 33, p. 311 (1976).
Efforts were made therefore to reach an adequate vaccination of poultry by preparation and use of combined vaccines derived from IBV strains of different serotypes corresponding with the IBV types. However, a clearly encountered difficulty appeared to form the decrease of immunogenic properties of the respective starting viruses caused by mutual interaction as appears from Am. J. Vet. Res. 36, 4, 524 and 525 (1965) and Avian Diseases 12, 577 (1968).
The most adequate improvement which has been obtained up to now against the present frequently occuring IB virus infections caused by viruses deviating from the ones which can be combatted with vaccines derived from the H-strain, was obtained by the preparation and use of combined vaccines derived from one or more of the IB viruses identified as Utrecht. 101, Utrecht. 102, Drente. 201, Limburg. 501, Limburg. 502, Brabant. 801, Limburg. 536, Overijssel. 728 and Utrecht. 121, as disclosed in the European patent application No. 0 030 063. However, there is still existing need for further improved IB vaccines with immunizing properties over a wider range and/or better immunogenic properties.
It will be appreciated that the pursed improvement of these vaccines is still severely hampered by the appearance of new serotypes of IB-viruses, the change of immunogenic and other properties of the presently available IB viruses after a large number of passages in embryonated chicken eggs and the lack of sufficiently effectively applicable serological and immunological test procedures. In this connection reference may be made to Avian Diseases, Vol. 19 No. 12, page 323 and 324 (1975).
As a result of extensive research and experimentation, novel IB viruses could surprisingly be obtained and determined, which deviate from the frequently applied IB viruses of the H type (e.g. IB H 120 and IB H 52), but show corresponding antigenic properties with the viruses described in the beforementioned European patent application. The frequently used IB viruses of the H-type deviates from new IB virus in cross neutralization tests (virus neutralization tests) according to e.g. the method as described in American Association of Avian Pathologists, "Isolation and Identification of Avian Pathogens", page 184 (1975), in the understanding that antisera diluted in a ratio of 1:5 are used, and in challenge experiments with subsequent virus reisolation tests. In other words, at an innoculation with a virus of the H-type (e.g. IB H 120 and IB H 52), the concerning animals are not protected against virus replication in the mucosa of the respiratory system after a challenge with one of the beforementioned deviating novel IB viruses. Antibodies against the IB H-strain equally appeared not to be able to neutralize significant amounts of IB virus of the novel deviating type.
Of special importance for the practice is that the novel IB virus causes respiratory symptoms with animals showing high antibody titers against the IB H-strain, and with still laying animals, egg production drops.
Each of the new IB virus generates after inoculation antibodies against not only itself, but also against the IB viruses different from the H-type strains, as mentioned in the above-cited European patent application. The new IB viruses therefore show a broad spectrum against the nowadays frequently occuring IB virus strains deviating from the ones which can be combatted with vaccines derived from the H-strain.
It is an object of the invention to provide novel infectious bronchitis viruses and vaccines prepared from the said viruses.
It is another object of the invention to provide novel combined infectious bronchitis vaccines and to novel processes for the preparation of the single or combined vaccines of the invention.
It is an additional object of the invention to provide novel methods of protecting poultry from infectious bronchitis.
These and other objects and advantages of the invention will become obvious from the following detailed description.
The novel infectious virus strains of the invention are novel serotypes of virus strain identified by the internal No. Brabant 802 and is deposited at the Czechoslovak National Collection of Type Cultures of the Institute of Hygiene and Epidemiology in Prague under No. CNCTC 18/82 and deposited at the Collection of Nationale d'Institute Pasteur, Paris under No. I-202 and a virus strain identified by the internal No. Gelderland 901 and is deposited at the Czechoslovak National Collection of Type Cultures of the Institute of Hygiene and Epidemiology in Prague under No. CNCTC AO 17/81 and deposited at the Collection Nationale de Cultures de Microorganismes d'Institute Pastuer, Paris under No. I-168.
These viruses were isolated by means of the trachea swab method from broiler chickens which showed at an age of 4-5 weeks respiratory symptoms after previous vaccination at the age of one day with IB vaccine of the H 120 type, whereby the animals found themselves at the moment of isolation in the district, which was indicated in the hereinbefore used internal notation (Gelderland and Brabant respectively). It was found that by attenuation to SPF-chicken embryos, the isolated virus strains lost their pathogenicity for SPF chickens to a major degree, in spite of the fact that its immunizing ability still remained present.
The virus strains with internal notation IBV Gelderland 901 (G. 901) and Brabant. 802 (B. 802) and deposited under Nos. CNCTC AO 17/81 and CNCTC AO 18/82 respectively and Nos. I-168 and I-202 respectively, showed these beforementioned characteristics after about 13, 45 and 90 SPF type I chicken embryo passages.
There was surprisingly found during a comparison test using conventional H 120 or H 52 vaccines that the protection against IB viruses of the Massachusetts type, measured as the amount of virus neutralizing antibodies, had not been diminished to a significant degree, if a H-type vaccine combined with the novel IBV isolate Gelderland. 901 or the IBV isolate Brabant. 802 was administered instead of the H-type vaccine alone. During this experimentation, one started from intranasal application of the concerning vaccines.
Cross neutralization tests in SPF chicken embryos and cross infection tests on SPF chickens were carried out giving results as shown in the following Tables 1, 2 and 3 and in FIG. 1. A neutralization index >2.0 means that the chickens involved were protected against the specific IBV infection.
TABLE I ______________________________________ Cross neutralization test in SPF chicken embryos. Infectious Neutralization index (N.I.) with antiserum bronchitis against infectious bronchitis virus testvirus H.52 G.901 O.728 L.536 U.101 ______________________________________ H.120 6.4 1.6 0.3 0.4 1.9 G.901 0.8 6.8 7.2 6.9 4.2 O.728 ND 6.5 ND ND ND L.536 ND 4,9 ND ND ND U.101ND 3,8 ND ND ND ______________________________________ The abbreviation "ND" means "not done".
TABLE 2 ______________________________________ Cross neutralization tests in SPF chicken embryos. Infectious Neutralization index (NI) with antiserum bronchitis against infectious bronchitis virus testvirus H.52 O.728 L.536 U.101 B.801 ______________________________________ B.802 0.4 3.6 2.1 2.8 3.3 ______________________________________
TABLE 3 ______________________________________ Cross infection tests with 4 week old SPF chickens. Vaccine virus Challenge virus Virus reisolation ______________________________________ IBV G.901 IBV G.901 0/5 positive IBV VOET (Massachusetts) 3/5 positive IBV O.728 0/5 positive IBV H.120 IBV G.901 4/5 positive IBV VOET (Massachusetts) 0/5 positive IBV O.728 5/5 positive ______________________________________ The vaccine virus was administered intranasally at a dose of 10.sup.4..sup.0 EID.sub.50 per bird.
The virus reisolation test was carried out 5 days after challenge using trachea swab material and the virus reisolation technique used is described in "Specifications for the production and control of avian live virus vaccines" of the Ministry of Agriculture, Fisheries and Food of the United Kingdom Central Veterinary Laboratory of Biological Products and Standards Department, New Haw, Weybridge, Surrey KT153 NB, 2nd Edition (1977), p. 12.
From the results of Tables 1, 2 and 3 (cross neutralization and cross infection tests), it appears that the applied serotype of the novel IBV G. 901 and IBV B. 802 differs anti-genitically from the H-strain and, having in mind the results of the challenge experiments with additional virus reisolation, shows attractive immunogenic properties as to the homologeous viruses as described in the abovementioned European Patent Application. Field experiments showed that in sera of broilers, reproduction chickens and laying hens, antibodies were frequently occuring against the virus type Gelderland. 901 and Brabant. 802.
In FIG. 1 the neutralization indices (vertical axis) determined for the IBV test viruses H. 120, Gelderland. 901, Overijssel. 728, Limburg. 536, Utrecht. 101 and Brabant. 801 respectively and for the homologeous test virus Gelderland. 901, are plotted for the six IBV anti sera types H.52, Gelderland. 901, Overijssel. 728, Limburg. 536, Utrecht. 101 and Brabant.801 on the horizontal axis. It will be appreciated therefore that the novel IB virus strains differs antigenitically in a significant degree from the usually applied H-virus and have common antigenic properties with the viruses of the beforementioned European application.
The novel isolated virus strains could be characterized by the following tests:
Chloroform treatment according to Mayr, et al, Virologische Arbeitsmethoden, G. Fischer Verlag, Jena, 1977, p. 285 of infectious amnion allantoic fluid obtained by cultivation of original virus containing samples from infected homogenized organ and trachea swab material in the allantoic cavity of 10 days preincubated SPF chicken eggs, resulted, in comparison with the untreated material, in a reduction of virus content from 107.5 to 101.5 EID50. This experience points to the presence of a virus agent which contains in his envelope a lipid which is necessary for the infectivity. The infectious amnion-allantoic fluid caused no agglutination with erythrocytes derived from SPF chickens.
Addition of 5-fluorodesoxyuridine (FUDR) to the culture medium of chicken kidney cell cultures serving for replication of the agent did not influence the intracellular synthesis of the virus agent to a significant degree.
The EID50 content of the cell material and culture medium appeared to reside on comparable levels 2, 4 and 7 days after the inoculation of the virus agent, i.e. the nucleic acid to be replicated belongs to the group of the ribonucleic acid.
Examination with electron microscope showed that the virus agent present in the amnion allantoic fluid harvested within 30 hours after the artificial infection possessed a diameter of about 100 nm. About 15 nm long projections were present on the surface of this virus and the virus has the size and shape of a corona virus to which also the avian bronchitis viruses are regarded to belong.
It will be appreciated that the properties of the novel serotype of the IB-viruses of the present invention make the novel virus strains especially suitable for the preparation of as well inactivated as live poultry vaccines on behalf of a more efficient protection against infectious bronchitis, especially in areas or countries wherein the described deviating serotype of the present application and the above-mentioned European patent application occur besides the IB viruses of the so called H-type.
More particularly, virus strains of the serotypes of the hereinbefore mentioned novel virus strains may successfully be used for the preparation of mixed live and inactivated vaccines derived as well from the novel IB strain as from the H-strain. It will be appreciated that novel IB vaccines of the present invention may be derived from the beforementioned novel strains G. 901 and B. 802 and mutants or variants thereof belonging to the same serotype.
The novel IBV vaccines of the present invention may be obtained by propagation of the novel virus strains by methods known in the art in principle and optionally followed by inactivation by methods known in the art in principle. For instance, the virus may be propagated in embryonated SPF chicken eggs or in suitable cell cultures such as chicken kidney cell cultures. However, with such a process, it has to be checked that the antigenic properties and the degree of virus replication do not significantly change. Then, the cultivated virus material is collected and purified and finally one or more stabilizers and, if desired, antibiotics such as sodium penicillin G, streptomycin or natamycin may be added and the mixture is lyophilized.
More particularly, the seed virus concerned is inoculated under sterile conditions into the allantoic cavity of 10-11 days preincubated SPF type I chicken eggs. After incubation for 28 to 48 hours at 37° C., the amnion-allantoic fluid of the then still living and of the specifically dead (i.e. between 24 hours after the seed virus inoculation and the end of the incubation period) embryos is harvested, purified and lyophilized after optional addition of stabilizers and/or antibiotics.
According to this process, single vaccines can be prepared containing the virus in an amount of at least 104.0 EID50 per dose after lyophilization, while e.g. so prepared combined vaccines of one of the novel virus strain and a known H-strain and/or more other IBV-strains showed a virus content of ≧2×104.0 EID50 per dose and preferably a content of each of the virus components of at least 104.0 EID50 per dose.
It will be appreciated that the present invention also relates to novel, inactivated as well as live, IBV vaccines which have been at least derived from one virus belonging to one of the serotypes of the novel IB virus strains G.901 and B.802 and to the use of such vaccines to protect poultry.
Preferably live vaccines derived from viruses of the serotypes of the novel virus G.901 or from the novel virus B.208 alone or from the H-type virus with the novel IB-virus are used. More preferably, live vaccines derived from H 120 or H 52 virus strain from viruses of the serotype of the G.901 virus strain or from the B.802, virus strain are used. The vaccines may also be administered to young chickens.
The novel live virus vaccines may be administered by the so called eyedrop- or nosedrop-, the drinking-water-or spray-methods. Vaccination of the novel live vaccines of the invention preferably is carried out with poultry of an age of 1 day to 18 weeks. The novel inactivated vaccines may be administered to the birds subcutaneously or intramuscularly and may be used for revaccination purposes only.
As examples of suitable inactivated combination vaccines as indicated hereinbefore may be mentioned those derived from the strains G.901, B.801 and H.52, derived from the strains, B.802, L.536 and H.52, derived from the strains G.901, B.802, B.801 and H.52 respectively. It will be appreciated that also combined live or inactivated vaccines derived from the novel IB strain type G.901 or B.802 and one or more completely other virus types such as e.g. the Newcastle disease virus, adenolike virus, infectious bursitis virus or reo virus, are a feature of the present invention too.
For the preparation of inactivated IBV vaccines of the invention, there may be started from e.g. an amnionallantoic fluid which may be diluted with PBS and to which a suitable carrier is added after inactivation by methods known in the art, e.g. by means of beta-propiolactone or formaline. Preferably, the virus suspension with a suitable virus content is processed to a water-in-oil emulsion vaccine derived from a mineral or plant oil and one of more emulsifiers such as non-ionic surface-active compounds derived from alkylene oxide and/or hexahydric alcohols and/or higher natural fatty acids (C10 -C20) such as esters or esterethers. Examples of the last mentioned emulsifiers are sorbitan or mannide monooleate (Span 80 ,Arlacel 80 ,Arlacel A ) and polyyoxyethylene (20) sorbitan monooleate (e.g. Tween 80 ). The volume ratio between the aqueous phase (virus fluid) and the oily phase may vary from 3:7 to 1:1 and lies preferably at a ratio of about 7:13. In the following examples there are described several preferred embodiments to illustrate the invention. However, it should be understood that the invention is not intended to be limited to specific embodiments.
Step A: Cultivation of virus
Type I SPF chicken egg preincubated for 10 to 11 days were inoculated into the allantoic cavity with 103.0 to 104.0 EID50 IBV G.901 seed virus (0.2 ml per egg) and the eggs were candled for the first time 20 to 24 hours after the virus inoculation and all aspecifically dead embryos were removed. After an incubation period of in total 28 hours at +37° C., the amnion-allantoic fluid (AAF) was harvested.
STEP B: Treatment of virus suspension
After purification of the AAF by centrifugation for 20 minutes at 2000 r.p.m. in a cooling centrifuge and/or by filtration, 5×105 units of sodium penicillin G and 800 mg of streptomycin per liter were added to the AAF. The virus material was subsequently stabilized by addition of at least 3% by weight of albumin and/or mannitol and the stabilized bulk virus material was frozen to at least -35° C. and stored at such temperature until the further processing phase.
Samples of this material were tested for their virus content by the EID50 (Egg Infectious Dose 50%) assay method. After the test results were available, the virus material was thawed and filled into lyophilization flasks. The virus content (volume) was adjusted in such a way that at the end of the subsequent lyophilization there were still at least 104.0 EID50 of the concerning virus per dose present in the vaccine. The flasks were sealed under vacuum at the end of the lyophilization process.
With the preparation of the multivalent (combined) vaccine, care has to be taken so that the minimum virus contents for all virus components reached.
STEP A: Cultivation of virus
Type I SPF chicken eggs which had been preincubated for 10 to 11 days were inoculated into the allantoic cavity with 103.0 to 104.0 EID50 of H.52 or G.901 seed virus (0.2 ml in total per egg) and the eggs were candled for the first time 20 to 24 hours after the virus inoculation. All aspecifically dead embryos were removed and after an incubation period of a total 32 hours at 37° C., the AAF was harvested.
STEP B: Treatment of the virus suspension
After purification of the AAF by centrifugation for 20 minutes at 2000 r.p.m. in a cooling centrifuge and/or by filtration, 8×105 units of sodium penicillin G and 1000 mg of streptomycin per liter were added to the AAF. The virus material was subsequently stabilized by addition of at least 3% by weight of albumin and/or mannitol and the stabilized bulk virus material was then frozen to at least -35° C. and kept at this temperature until further processing.
Meanwhile, samples of this material were tested for their virus content by the EID50 assay method. The virus material was thawed and filled out into lyophilization flasks after the test results were available. The virus content (volume) was adjusted in such a way that at the end of the lyophilization process, the vaccine contained per dose at least 104.0 EID50 of each virus concerned. The flasks were sealed under vacuo at the end of the lyophilization process. During the preparation of the multivalent (combined) vaccine, care had to be taken that the minimum virus content for all virus components was reached.
In a manner similar to Example 2A, the virus was cultivated in SPF eggs and the obtained virus suspension was treated in a similar way as in Example 2B until the frozen phase was reached but without addition of antibiotics and stabilizers. The frozen AAF was thawed and inactivated in a water bath by 0.1% of beta-propiolactone for a period of 90 minutes at 37° C. Then, the virus suspension was kept overnight at +4° C. and the inactivation was checked by inoculation of preincubated, embryonated SPF chicken eggs with the inactivated virus material and subsequent incubation.
The AAF's of strain H.52 and of strains G.901 were mixed in a ratio of 3:2 and the mixed inactivated AAF was diluted, if necessary, with PBS+0.3% of formaline depending on the virus content of each virus type determined in the noninactivated AAF (to a concentration of at least 107.0 EID50 per ml for all virus strains). 3.5% of Tween 80 were added to the virus suspension of the two strains and the inactivated virus suspension was mixed with an oil phase in the ratio of 6.5 parts of oil to 3.5 parts of virus fluid and emulsified so that the average particle size of the aqueous phase was about 0.5μ.
The emulsification was carried out with an Ultra Turrax homogenizer or by passing the starting mixture through a colloid mill. The oil phase had the following composition: Marcol 5 2 (white paraffinic Esso oil) 93.5% Arlacel A ,Arlacel 80 or Span 80 (mannide monooleate) 6.5%.
The components of the oil phase were separately heated to 110° C. in an autoclave or the mixture was sterilized by filtration.
The B.801 virus and the G.901 virus were cultivated in SPF eggs in the same way as described in Example 1 for the G.901 virus strain and H.52 virus containing AAF was prepared in the same way as in Example 2. The treatment of the virus suspensions of the three strains was carried out according to the corresponding steps of Example 3 until the inactivated AAF's were mixed. The inactivated AAF of strain H.52 was then mixed with the AAF of strain G.901 and of strain B.801 in the ratio of 8:3:3. The mixed inactivated AAF was diluted, if necessary, with PBS+0.3% of formaline depending on the virus conent of each virus type determined in the non-inactivated AAF (at least 107.0 EID50 per ml for all virus strains). 2.6% of Tween 80 were added to the virus suspension of the three strains and the inactivated virus suspension was mixed with an oil phase in the ratio of 6.0 parts of oil to 4.0 parts of virus fluid and emulsified so that the average particle size of the aqueous phase was about 0.5μ. The emulsification was carried out with an Ultra Turrax homogenizer or by passing the starting mixture throught a colloid mill. The composition of the oil phase was the same as in Example 3.
Cultivation of virus and treatment of the virus suspension was carried out according to the corresponding steps of Example 1, but AAF was harvested after an incubation period of 32 hours at 37° C. instead of 28 hours.
The B.802 virus and L.536 virus were cultivated in SPF eggs in the same way as described in Example 1 for the G.901 virus, but an incubation period of 32 hours was taken before AAF was harvested. H.52 virus was cultivated in the same way as in Example 2 and the treatment of virus suspensions of the three strains was carried out according to the corresponding steps in Example 4. The inactivated AAF's of strain H.52, strain B. 802 and strain L.356 were mixed in the ratio 3:1:1 and further treatment and emulsification was carried out as described in Example 4.
The B.802 virus and G.901 virus were cultivated in SPF eggs in the same way as described in Example 1 for the G.901 virus, but an incubation period of 32 hours was taken before AAF was harvested and H.52 virus was cultivated in the same way as in Example 2. The treatment of the virus suspensions of the three strains was carried out according to the corresponding steps in Example 4 and the inactivated AAF's of strain H.52, strain B.802 and strain G.901 were mixed in the ratio 3:1:1. Further treatment and emulsification was carried out as described in Example 4.
Various modifications of the products and processes of the invention may be made without departing from the spirit or scope thereof and it is to be understood that the invention is to be limited only as defined in the appended claims.
Claims (5)
1. A combined infectious bronchitis water-in-oil emulsion oil-adjuvant vaccine having a volume ratio between the aqueous phase and the oily phase from 3:7 to 1:1 of at least 104.0EID.50 per dose of each of the virus components of inactivated vaccine derived from at least one virus strain selected from the group consisting of .Iadd.a serotype of .Iaddend.infectious bronchitis virus strain identified by the internal notation Gelderland. 901 deposited at the Czechoslovak National Collection of Type Cultures of the Institute of Hygiene and Epideminology in Prague under No. CNCTC AO 17/81 and deposited at the Collection Nationale de Cultures de Micro organismes d'Institute Pasteur, Paris, under No. I-168 and .Iadd.a serotype of .Iaddend.infectious bronchitis virus strain by the internal notation Brabant. 802, deposited at the Czechoslovak National Collection of Type Cultures of the Institute of Hygiene and Epidemiology in Prague under No. CNCTC 18/82 and deposited at the Collection Nationale d'Institute Pasteur, Paris, under No. I-202 combined with a second vaccine derived from the IBV H120 or the IBV H52 of the Massachusetts type.
2. An infectious bronchitis vaccines of claim 1 wherein the second vaccine is derived from the IBV H 52 of the Massachusetts type.
3. An inactivated infections bronchitis vaccine of claim 1 or 2 wherein they contain an oily phase containing at least a mineral oil, or vegetable oil and at least one suitable emulsifying agent in the form of a non-iogenic surface active agent derived from alkylene oxide and/or hexahydric alcohols and/or higher natural fatty acids of 10-20 carbon atoms.
4. A method of protecting poultry against infectious bronchitis comprising vaccinating poultry with an amount of a vaccine of claim 1 sufficient to protect the poultry against infectious bronchitis.
5. The method of claim 4 wherein the second vaccine of IBV H 52 of the Massachusetts type.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NL81-200960.3 | 1981-08-28 | ||
EP19810200960 EP0073856A1 (en) | 1981-08-28 | 1981-08-28 | Infectious-bronchitis vaccines for poultry, combined infectious-bronchitis vaccines, process for preparing such vaccines, process for preventing infectious bronchitis and infectious-bronchitis virus strain |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US06/409,996 Reissue US4481188A (en) | 1981-08-28 | 1982-08-20 | Vaccines |
Publications (1)
Publication Number | Publication Date |
---|---|
USRE32283E true USRE32283E (en) | 1986-11-11 |
Family
ID=8188146
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US06/409,996 Ceased US4481188A (en) | 1981-08-28 | 1982-08-20 | Vaccines |
US06/621,077 Expired - Fee Related US4692410A (en) | 1981-08-28 | 1984-06-15 | Infections bronchitis virus strains |
US06/621,078 Expired - Fee Related US4645665A (en) | 1981-08-28 | 1984-06-15 | Live infectious bronchitis vaccine for poultry |
US06/682,859 Expired - Fee Related USRE32283E (en) | 1981-08-28 | 1984-12-18 | Vaccines |
US06/893,936 Expired - Fee Related US4761282A (en) | 1981-08-28 | 1986-08-06 | Inactivated infectious bronchitis vaccine for poultry |
Family Applications Before (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US06/409,996 Ceased US4481188A (en) | 1981-08-28 | 1982-08-20 | Vaccines |
US06/621,077 Expired - Fee Related US4692410A (en) | 1981-08-28 | 1984-06-15 | Infections bronchitis virus strains |
US06/621,078 Expired - Fee Related US4645665A (en) | 1981-08-28 | 1984-06-15 | Live infectious bronchitis vaccine for poultry |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US06/893,936 Expired - Fee Related US4761282A (en) | 1981-08-28 | 1986-08-06 | Inactivated infectious bronchitis vaccine for poultry |
Country Status (11)
Country | Link |
---|---|
US (5) | US4481188A (en) |
EP (2) | EP0073856A1 (en) |
JP (1) | JPS5874618A (en) |
CA (1) | CA1204055A (en) |
DE (1) | DE3266201D1 (en) |
DK (1) | DK163133C (en) |
ES (2) | ES515321A0 (en) |
GR (1) | GR76902B (en) |
IE (1) | IE53872B1 (en) |
PT (1) | PT75412B (en) |
ZA (1) | ZA826154B (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4761282A (en) | 1981-08-28 | 1988-08-02 | Gist-Brocades N.V. | Inactivated infectious bronchitis vaccine for poultry |
US5750113A (en) * | 1993-07-30 | 1998-05-12 | Akzo Nobel N.V. | Poultry vaccine |
Families Citing this family (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2114438A (en) * | 1982-02-05 | 1983-08-24 | Akzo Nv | Infectious bronchitis vaccines |
NL8301996A (en) * | 1983-06-06 | 1985-01-02 | Duphar Int Res | METHOD FOR PREPARING ADVISED LIVE VACCINES AND SO OBTAINED VACCINES OBTAINED. |
IL74289A (en) * | 1985-02-10 | 1989-02-28 | Israel State | Vaccine system comprising a live-non-virulent vaccine and an adjuvant |
ATE66818T1 (en) * | 1985-07-18 | 1991-09-15 | Duphar Int Res | VACCINE FOR DAY-OLD CHICKENS AGAINST INFECTIOUS BRONCHITIS. |
HUT43110A (en) * | 1985-10-31 | 1987-09-28 | Duphar Int Res | New antigene-active proteines and peptides and infective bronchitis virus /ibv/ vaccines |
FR2602791B1 (en) * | 1986-08-18 | 1988-11-10 | Ministere Agri Direction Quali | METHOD FOR CULTURING TURKEY INFECTIOUS RHINOTRACHEITIS VIRUS, AND VACCINE PREPARED FROM THE VIRUS OBTAINED THEREBY |
US4824668A (en) * | 1987-03-09 | 1989-04-25 | Sterwin Laboratories Inc. | Attenuated infectious bursal disease virus strain and vaccine therefrom |
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 |
US5250298A (en) * | 1988-10-07 | 1993-10-05 | University Of Delaware | Live attenuated newcastle disease virus vaccines and preparation thereof |
US5397568A (en) * | 1989-10-02 | 1995-03-14 | Whitfill; Craig E. | Method of treating infectious bursal disease virus infections |
ATE150976T1 (en) * | 1989-10-02 | 1997-04-15 | Univ Arkansas | VACCINE CONJUGATES FOR THE TREATMENT OF BIRD DISEASES |
JP3078013B2 (en) * | 1989-10-02 | 2000-08-21 | エンブレックス インコーポレイテッド | Uses of vaccine conjugates, vaccine preparations and articles of manufacture |
US5688761A (en) * | 1991-04-19 | 1997-11-18 | Lds Technologies, Inc. | Convertible microemulsion formulations |
JPH06507172A (en) * | 1991-04-19 | 1994-08-11 | アフィニティー バイオテック,インコーポレイテッド | Convertible microemulsion formulation |
US5888518A (en) * | 1995-10-06 | 1999-03-30 | Beretich, Sr.; Guy R. | Method for preventing and treating coccidiosis |
EP2545937A1 (en) * | 2001-06-05 | 2013-01-16 | The Regents Of The University Of Michigan | Nanoemulsion vaccines |
KR100468037B1 (en) * | 2002-01-04 | 2005-01-24 | 학교법인 건국대학교 | New infectious bronchitis viruses and vaccines for preventing infectious bronchitis using the same |
US20050208083A1 (en) * | 2003-06-04 | 2005-09-22 | Nanobio Corporation | Compositions for inactivating pathogenic microorganisms, methods of making the compositons, and methods of use thereof |
CA2604392A1 (en) * | 2005-04-11 | 2006-10-19 | Nanobio Corporation | Quaternary ammonium halides for treatment of infectious conditions |
WO2008051186A2 (en) * | 2005-08-09 | 2008-05-02 | Nanobio Corporation | Nanoemulsion containing compositions having ant i -inflammatory activity |
US10138279B2 (en) | 2006-04-13 | 2018-11-27 | Regents Of The University Of Michigan | Compositions and methods for Bacillus anthracis vaccination |
US20080038295A1 (en) * | 2006-04-13 | 2008-02-14 | Regents Of The University Of Michigan | Compositions and methods for orthopox virus vaccination |
US9839685B2 (en) * | 2006-04-13 | 2017-12-12 | The Regents Of The University Of Michigan | Methods of inducing human immunodeficiency virus-specific immune responses in a host comprising nasally administering compositions comprising a naonemulsion and recombinant GP120 immunogen |
US9415006B2 (en) * | 2008-05-23 | 2016-08-16 | The Regents Of The University Of Michigan | Immunogenic compositions comprising nanoemulsion and hepatitis B virus immunogen and methods of using the same |
JP6110140B2 (en) * | 2009-06-16 | 2017-04-05 | ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン | Nanoemulsion vaccine |
US9492548B2 (en) * | 2012-12-14 | 2016-11-15 | Intervet Inc. | Emulsion containing a non-live medicinal substance |
CN104762271A (en) * | 2015-01-26 | 2015-07-08 | 河南科技学院 | Preparation method and use of duck-derived coronavirus attenuated strain DCV35 |
BR102020019867A2 (en) * | 2020-09-28 | 2022-04-12 | Fundacao Univ Estadual Do Ceara Funece | Use of avian coronavirus vaccine (ibv) as a model of immunization in mammals against sars-cov 2 |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US31830A (en) * | 1861-03-26 | Water-meter | ||
JPS4872317A (en) * | 1971-12-29 | 1973-09-29 | ||
JPS529727A (en) * | 1975-07-11 | 1977-01-25 | Toyota Motor Corp | Carburettor |
JPS5276421A (en) * | 1975-12-17 | 1977-06-27 | Kitasato Inst | Nephritis type pourtry infectious bronchitis vaccine and production of blended vaccine |
NL7904021A (en) * | 1979-05-22 | 1980-04-29 | Gist Brocades Nv | COMBINED VACCINE AND METHOD FOR PREPARING THIS COMBINED VACCINE AGAINST ADENO-LIKE VIRUSES DROP IN EGG PRODUCTION DROPS AND DISEASES CAUSED BY REO VIRUS. |
EP0030063A2 (en) * | 1979-11-30 | 1981-06-10 | Gist-Brocades N.V. | Infectious-bronchitis vaccines for poultry, combined infectious-bronchitis vaccines, process for preparing such vaccines, process for preventing infectious bronchitis and infectious-bronchitis virus strains |
JPS5692823A (en) * | 1979-11-30 | 1981-07-27 | Gist Brocades Nv | Infectious bronchitis vaccine for poultry and its manufacture |
US4357320A (en) * | 1980-11-24 | 1982-11-02 | Gist-Brocades N. V. | Infectious bronchitis vaccine for poultry |
EP0073547A1 (en) * | 1981-08-28 | 1983-03-09 | Gist-Brocades N.V. | Infectious-bronchitis vaccines for poultry, combined infectious-bronchitis vaccines, process for preparing such vaccines and infectious-bronchitis virus strain |
USRE31830E (en) | 1979-11-13 | 1985-02-12 | Gist-Brocades N.V. | Infectious bronchitis vaccine for poultry |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US32283A (en) * | 1861-05-14 | Fireplace |
-
1981
- 1981-08-28 EP EP19810200960 patent/EP0073856A1/en not_active Withdrawn
-
1982
- 1982-08-11 PT PT7541282A patent/PT75412B/en not_active IP Right Cessation
- 1982-08-17 CA CA000409580A patent/CA1204055A/en not_active Expired
- 1982-08-20 US US06/409,996 patent/US4481188A/en not_active Ceased
- 1982-08-24 ZA ZA826154A patent/ZA826154B/en unknown
- 1982-08-25 JP JP57148488A patent/JPS5874618A/en active Pending
- 1982-08-26 DE DE8282201061T patent/DE3266201D1/en not_active Expired
- 1982-08-26 EP EP19820201061 patent/EP0073547B1/en not_active Expired
- 1982-08-27 ES ES515321A patent/ES515321A0/en active Granted
- 1982-08-27 IE IE2078/82A patent/IE53872B1/en not_active IP Right Cessation
- 1982-08-27 DK DK384782A patent/DK163133C/en not_active IP Right Cessation
- 1982-08-27 GR GR69142A patent/GR76902B/el unknown
-
1983
- 1983-08-16 ES ES524968A patent/ES524968A0/en active Granted
-
1984
- 1984-06-15 US US06/621,077 patent/US4692410A/en not_active Expired - Fee Related
- 1984-06-15 US US06/621,078 patent/US4645665A/en not_active Expired - Fee Related
- 1984-12-18 US US06/682,859 patent/USRE32283E/en not_active Expired - Fee Related
-
1986
- 1986-08-06 US US06/893,936 patent/US4761282A/en not_active Expired - Fee Related
Patent Citations (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US31830A (en) * | 1861-03-26 | Water-meter | ||
JPS4872317A (en) * | 1971-12-29 | 1973-09-29 | ||
JPS529727A (en) * | 1975-07-11 | 1977-01-25 | Toyota Motor Corp | Carburettor |
JPS5276421A (en) * | 1975-12-17 | 1977-06-27 | Kitasato Inst | Nephritis type pourtry infectious bronchitis vaccine and production of blended vaccine |
NL7904021A (en) * | 1979-05-22 | 1980-04-29 | Gist Brocades Nv | COMBINED VACCINE AND METHOD FOR PREPARING THIS COMBINED VACCINE AGAINST ADENO-LIKE VIRUSES DROP IN EGG PRODUCTION DROPS AND DISEASES CAUSED BY REO VIRUS. |
USRE31830E (en) | 1979-11-13 | 1985-02-12 | Gist-Brocades N.V. | Infectious bronchitis vaccine for poultry |
JPS5692823A (en) * | 1979-11-30 | 1981-07-27 | Gist Brocades Nv | Infectious bronchitis vaccine for poultry and its manufacture |
EP0030063A2 (en) * | 1979-11-30 | 1981-06-10 | Gist-Brocades N.V. | Infectious-bronchitis vaccines for poultry, combined infectious-bronchitis vaccines, process for preparing such vaccines, process for preventing infectious bronchitis and infectious-bronchitis virus strains |
US4505892A (en) * | 1979-11-30 | 1985-03-19 | Gist-Brocades N.V. | Infectious bronchitis vaccine for poultry |
US4357320A (en) * | 1980-11-24 | 1982-11-02 | Gist-Brocades N. V. | Infectious bronchitis vaccine for poultry |
EP0073547A1 (en) * | 1981-08-28 | 1983-03-09 | Gist-Brocades N.V. | Infectious-bronchitis vaccines for poultry, combined infectious-bronchitis vaccines, process for preparing such vaccines and infectious-bronchitis virus strain |
EP0073856A1 (en) * | 1981-08-28 | 1983-03-16 | Gist-Brocades N.V. | Infectious-bronchitis vaccines for poultry, combined infectious-bronchitis vaccines, process for preparing such vaccines, process for preventing infectious bronchitis and infectious-bronchitis virus strain |
US4481188A (en) * | 1981-08-28 | 1984-11-06 | Gist-Brocades N.V. | Vaccines |
Non-Patent Citations (6)
Title |
---|
Darbyshire et al., Archives of Virology 61: 227 238 (1979) Taxonomic Studies on Strains of Avian Infectious Bronchitis Virus Using Neutralization Tests in Tracheal Organ Cultures . * |
Darbyshire et al., Archives of Virology 61: 227-238 (1979) "Taxonomic Studies on Strains of Avian Infectious Bronchitis Virus Using Neutralization Tests in Tracheal Organ Cultures". |
Winterfield Avian Dis. 12: 577 584 (1968) Respiratory Signs, Immunity Response, and Interference From Vaccination With Monovalent and Multivalent Infectious Bronchitis Vaccines. * |
Winterfield Avian Dis. 12: 577-584 (1968) Respiratory Signs, Immunity Response, and Interference From Vaccination With Monovalent and Multivalent Infectious Bronchitis Vaccines. |
Winterfield et al., Am. J. Vet. Res. 36: 524 526 Apr. 1975, Potential for Polyvalent Infectious Bronchitis Vaccines. * |
Winterfield et al., Am. J. Vet. Res. 36: 524-526 Apr. 1975, Potential for Polyvalent Infectious Bronchitis Vaccines. |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4761282A (en) | 1981-08-28 | 1988-08-02 | Gist-Brocades N.V. | Inactivated infectious bronchitis vaccine for poultry |
US5750113A (en) * | 1993-07-30 | 1998-05-12 | Akzo Nobel N.V. | Poultry vaccine |
Also Published As
Publication number | Publication date |
---|---|
ZA826154B (en) | 1983-10-26 |
IE822078L (en) | 1983-02-28 |
CA1204055A (en) | 1986-05-06 |
PT75412B (en) | 1984-11-26 |
EP0073856A1 (en) | 1983-03-16 |
GR76902B (en) | 1984-09-04 |
ES8401128A1 (en) | 1983-12-01 |
EP0073547A1 (en) | 1983-03-09 |
ES8502871A1 (en) | 1985-02-01 |
JPS5874618A (en) | 1983-05-06 |
US4481188A (en) | 1984-11-06 |
US4761282A (en) | 1988-08-02 |
US4692410A (en) | 1987-09-08 |
US4645665A (en) | 1987-02-24 |
ES515321A0 (en) | 1983-12-01 |
IE53872B1 (en) | 1989-03-29 |
PT75412A (en) | 1982-09-01 |
DK384782A (en) | 1983-03-01 |
ES524968A0 (en) | 1985-02-01 |
EP0073547B1 (en) | 1985-09-11 |
DK163133C (en) | 1992-06-15 |
DK163133B (en) | 1992-01-20 |
DE3266201D1 (en) | 1985-10-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
USRE32283E (en) | Vaccines | |
Fahey et al. | Laryngotracheitis herpesvirus infection in the chicken: the role of humoral antibody in immunity to a graded challenge infection | |
JP2007125039A (en) | Chicken anaemia agent vaccine | |
US4357320A (en) | Infectious bronchitis vaccine for poultry | |
EP0030063B1 (en) | Infectious-bronchitis vaccines for poultry, combined infectious-bronchitis vaccines, process for preparing such vaccines, process for preventing infectious bronchitis and infectious-bronchitis virus strains | |
US4302444A (en) | Vaccines for immunizing egg-laying birds against Egg Drop disease, preparation of said vaccines, and method of use of said vaccines | |
US4751079A (en) | Infectious bronchitis vaccines | |
AU759179B2 (en) | Novel antigenic class of avian reoviruses | |
US4500638A (en) | Infectious bronchitis virus strain | |
JP3945842B2 (en) | Attenuated Newcastle disease virus vaccine | |
US20080317776A1 (en) | Vaccines Containing Viruses Involved in Avian Malabsorption Syndrome and Methods of Administration Therefor | |
USRE31830E (en) | Infectious bronchitis vaccine for poultry | |
US5686077A (en) | Methods of immunization of poultry with vaccines against chicken anemia agent (CAA) | |
EP0009277B1 (en) | Combined vaccine active against newcastle disease and egg production drop caused by adeno-like viruses, process for preparing it, adeno-like and newcastle disease virus strains | |
USRE32423E (en) | Infectious bronchitis virus strain | |
USRE34013E (en) | Infectious bronchitis vaccine for poultry | |
JPS6244528B2 (en) | ||
CA1184116A (en) | Infectious bronchitis vaccines for poultry and process for the preparation of such vaccines | |
US20040157212A1 (en) | Novel Avian reoviruses capable of immediate growth on mammalian cells | |
NL8005083A (en) | Infectious bronchitis vaccines for poultry - derived from novel virus serotype(s) isolated from chickens vaccinated with H-type vaccines |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FPAY | Fee payment |
Year of fee payment: 4 |
|
FEPP | Fee payment procedure |
Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
FPAY | Fee payment |
Year of fee payment: 8 |
|
REMI | Maintenance fee reminder mailed | ||
LAPS | Lapse for failure to pay maintenance fees |