WO1987004624A1 - Vaccin contre la peritonite infectieuse des felins - Google Patents

Vaccin contre la peritonite infectieuse des felins Download PDF

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Publication number
WO1987004624A1
WO1987004624A1 PCT/US1987/000216 US8700216W WO8704624A1 WO 1987004624 A1 WO1987004624 A1 WO 1987004624A1 US 8700216 W US8700216 W US 8700216W WO 8704624 A1 WO8704624 A1 WO 8704624A1
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WIPO (PCT)
Prior art keywords
virus
fipv
temperature
passage
cats
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PCT/US1987/000216
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English (en)
Inventor
Charles A. Baldwin
Fredric W. Scott
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Schering Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Schering Corporation filed Critical Schering Corporation
Priority to KR1019880700238A priority Critical patent/KR950002983B1/ko
Publication of WO1987004624A1 publication Critical patent/WO1987004624A1/fr

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/12Viral antigens
    • A61K39/215Coronaviridae, e.g. avian infectious bronchitis virus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/12Viral antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525Virus
    • A61K2039/5254Virus avirulent or attenuated
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/54Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A61K2039/541Mucosal route
    • A61K2039/543Mucosal route intranasal
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/55Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
    • A61K2039/552Veterinary vaccine
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2770/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011Details
    • C12N2770/20011Coronaviridae
    • C12N2770/20034Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • This invention relates to the immunization of felines against ⁇ oronavirus (FIPV) induced infectious peritonitis (FIP).
  • Coronaviruses which have been isolated from cats can be divided into two groups: viruses which cause FIP and viruses which cause a transient subclinical to severe enteritis.
  • the various isolates are all morphologically and antigenically related and probably represent stains of a common species of virus that infects cats, dogs and swine; (see Pedersen et al, Adv. Exp. Med. Biol., 173:365-380 (1984)).
  • FIPV 79-1146 is a virus strain originally isolated by James F. Evermann, Washington State University and has been characterized inter alia by McKeirnan et al. Feline Practice, 11.16-20 (1981);
  • feline infectious peritonitis virus WSU FIPV 79-1146 can be attenuated to form a live modified vaccine against feline infectious peritonitis (FIP) which vaccine both imparts immunity and is safe, that is does not cause FIP in the feline.
  • FIP feline infectious peritonitis
  • the present invention relates to a method of protecting felines against FIP, a method of producing a non-virulent attenuated living FIPV for use as a safe, efficacious vaccine, and the resultant vaccine.
  • the attenuation of the virus is accomplished by serial passaging in cell culture, preferably non- oncogenic cell culture, in which virus growth occurs, at a temperature which causes virus growth and attenuation until a non-virulent immunizing virus is produced.
  • Felines vaccinated with the attenuated strain did not suffer significant illness when challenged by a virulent strain of FIPV.
  • the cell culture employed in passaging the virus can be any cell culture in which the virus repli ⁇ cates, for example, whole fetus cells (e.g. FCWF, felis catus whole fetus), feline kidney cells (e.g. CrFK, Crandell Feline Kidney) , feline lung cells and A-72 (a canine tumor cell line).
  • the cell culture is a non-oncogenic cell culture. See also U.S. Patent 4,195,130, previously incorporated.
  • the temperature at which the virus is grown can be any temperature at which with tissue culture passage
  • the presently preferred temperature is a sub-optimal temperature, that is a temperature lower than the normal body temperature for a feline but at which virus growth occurs.
  • the presently preferred temperature range is between about 33°C'and about 35°C.
  • the number of passages required to obtain safe, immunizing attenuated virus is dependent at least in part on the conditions employed and in part on the age of the felines being vaccinated. Periodic testing of the culture for virulence and immunizing ability can readily determine the parameters for a particular combination of tissue culture and temperature.
  • a safe useful vaccine for all felines is at least about 35 passages and preferably at least about 40 passages.
  • a safe useful vaccine for adult felines i.e. felines six months old or older
  • an attenuated live FIP vaccine is produced by serially passaging the native virulent virus WSU FIPV 79-1146 at least about forty times in CrFK at a temperature between about 33°C and about 35°C.
  • the vaccine of this invention can be administered by any route which causes an increase in antibody titer in the feline.
  • the presently preferred route is intranasal or oral administration.
  • Subcutaneous administration is also contemplated as effective.
  • the virus used in the Examples was the strain WSU FIPV 79-1146, originally isolated by Dr. J.F. Evermann at Washington State University. It was supplied, at approximately the sixth passage level, to the Cornell Feline Health Center by Dr. Neils Pedersen from the University of California at Davis. The original isolate was made from a kitten that had died soon after birth of pneumonia and pleuritis. Direct examination of the virus by electron microscopy demonstrated two popula ⁇ tions present morphologically. One population, constituting 95-98% of the virions seen, was the typical FIPV with short, more tear-dropped-shaped peplomers. The other population was approximately 2-5% of the virions present and had longer, more bulbous-shaped peplomers present. Since it appeared that a mixed isolate was present, the virus was plaque purified and cloned, as described below, three times prior to use in these experiments.
  • the UCD1 strain of FIPV employed as a challenge virus was originally obtained from Dr. Neils Pedersen at , the University of California, Davis. The prior history of the virus included several passages through minimal disease cats. A 50% liver suspension was made upon the death of the cats at each passage and the suspension was stored at -70°C prior to its being used as a challenge virus.
  • the UCDl virus strain is a highly virulent one and has been used as a challenge virus at the Cornell Feline Health Center for many years. It consistently
  • FCWF's Felis catus whole fetus cells
  • FCWF's Felis catus whole fetus cells
  • Growth media for these cells included equal volumes of Leibowitz's (L15) (Gibco Grande Island Co., Grande Island, New York) and Dulbecco's modified minimal essential media (DMEM) (GIBCO) supplemented with 10% fetal bovine serum. It was found to be necessary to include in the growth media 0.05% Lactalbumin hydrosylate (LAH) (GIBCO), 1% MEM sodium pyruvate and 1% nonessential amino acids (GIBCO) .
  • LAH Lactalbumin hydrosylate
  • MEM pyruvate
  • nonessential amino acids GIBCO
  • the antibiotics Fungizone and Gentamicin were also added. When the cells had grown to a complete monolayer, they were split and transferred.
  • Media used to propagate the cells consisted of 20% L 15 , 3% 0.1 N NaOH, 2% L-glutamine (GIBCO). To transfer the cells, the growth media was removed and, depending on the size of the tissue culture flask, up to 7 cc of crude porcine trypsin-versine in phosphate buffered saline were added as a wash.
  • this trypsin wash was removed and a second volume of the trypsin was added.
  • the flask was incubated for 5-10 minutes at 37°. After the time had elapsed and when the cells had been dispersed into single cells, new growth media was added to a volume three times the original volume, for a one to three cell split. The cells were then dispensed into the new flasks as the protocol demanded.
  • the growth medium was removed from complete monolayers and the cells were washed once with MEM. This was removed and the viral inoculum was added. The flask was rocked on a Belco Low-
  • the antibiotics Fungizone and Gentamicin were added.
  • the plates were examined daily for plaque -production.
  • the clones were picked with the use of tuberculin syringes with 1" or 1 1/2" 20 gauge needles, and the clone was added to a vial containing 1 cc of MEM. If not inoculated immediately into flasks, the clones were frozen at -70°C for future use.
  • the plates were stained with a solution consisting of one gram crystal-violet per liter of 10% buffered formalin solution and examined to determine which was the most isolated of the plaque(s) picked. The isolated clones that had been picked were then grown up and the virus was replaqued for more clones. After the
  • the LP virus was passaged several more times in 480 cmr roller bottles but at 34°C.
  • passage level 16 a large flask was inoculated with virus, adsorbed for one hour with continuous rolling and maintenance media added.
  • the flask was frozen and thawed for three times.
  • the virus was then stored and was designated high passage virus (HP) . It was approximately passage level 17 and had only been propagated at 34°C since the plaque purifi ⁇ cation procedure. This HP virus was also considered to be a temperature-sensitive and was used as vaccine virus.
  • VN virus neutralization tests
  • serum samples were heat inactivated for 35 minutes in a 56°C water bath. After heat inactivation, two fold dilutions of serum were made in either MEM, L15 or PBS. An equal volume of virus containing 100 TCID 50 was then added to each serum sample. The serum-virus mixture was then incubated for one hour at 37°C. Following incubation, 0.2 cc of the serum-virus mixture was added in triplicate wells to a 48-well Costar plate that had been just seeded with CRFK cells. For the virus control, only 0.1 cc was added to each well. The tissue culture control had 0.1 cc of the diluent added to each well.
  • the plates were then sealed in plastic bags and incubated at 37°C for 4 days. On the fourth day, the medium was removed and the plate immersed in a crystal violet staining tank containing 10% formalin for 10 minutes. The plates were rinsed with water, allowed to dry and the
  • SUBSTITUT sample was titered.
  • the end point titer was considered to be the last dilution in which there was complete neutralization of the virus or in which there was complete protection of the cell monolayer.
  • the coverslips were then washed twice in distilled water, washed twice for 15 seconds in acetone, dehydrated in acetone-xylene mixtures, and finally immersed in pure xylene for ten minutes.
  • the coverslips were then removed, mounted on glass microscope slides for a permanent record using Permount (Fisher Scientific, Fairlawn, NJ) and examined.
  • the 11th Cornell passage of FIPV 79-1146 was used as challenge virus for the intra- tracheal "1st vaccination" or virus titration (Table 1). Attenuation of virus was done by rapid passage in cell cultures at low temperature (34°C). A total of 7 low temperature passages were done in a sequence of canine A-72 cells (3 passages) , and Crandell feline kidney cells (CrFK) (4 passages). The attenuated virus (19 passage attenuated virus) used in this study had 7 low temperature (34°C) CrFK cell culture passages and a total of 19 cell culture passages.
  • the results of the viral titration or "1st vaccination” are listed in Table 1.
  • the minimal infectious dose was 10 3 plaque forming units (PFU) of virus.
  • PFU plaque forming units
  • One of 2 cats receiving 10 3 PFU of virus became and infected and died on day 56 after inoculation.
  • Cat R4 developed FIP and died on day 28.
  • Three cats that seroconverted to FIPV 79-1146 did not show any signs of illness.
  • Cat Q3 was euthanized on day 60 after challenge because it was showing chronic FIP similar to what it had shown for several weeks following the initial inoculation.
  • Fever was detected in cat S2 (UCD- challenge) on days 8-12, anorexia on days 8-14, and icteric serum on day 14 after challenge.
  • Substantial neutralizing antibody titers against FIPV 79-1146 were produced following a single intranasal vaccination.
  • the VN antibody titers were listed in Table 2.
  • UCD-i Liver suspension of virulent virus infected with 100 TCID5 Q of virus
  • KMC neonatal kitten with kitten mortality complex
  • Table 3 lists the experimental design for experiment 85-01, the evaluation of passage 19 attenuated virus in 12- to 16-week old kittens each.
  • Group A served as unvaccinated controls
  • Group B received 0.5 ml (100,000 TCID 5 Q) of vaccine virus intranasally
  • Group C received the same dose of vaccine subcutaneousl .
  • the individual and group mean temperatures of cats in this experiment are listed in Table 4 (Groups A, B, and C) .
  • the individual and group mean clinical scores are listed in Table 5.
  • the viral isolation results from pharyngeal swabs are listed in Table 6, and the virus neutralizing titers are given in Table 7.
  • Virus was isolated from pharyngeal swabs from all 6 kittens receiving intranasal vaccine (Table 6). Virus was present by 1 day after vaccination in all cats, 5 of 6 were still positive for virus on day 6, but only 2 of 6 kittens had virus on day 8. All kittens were negative by day 11 after vaccination.
  • Virus neutralizing antibody titers in sera were low at day 7, then increase in each weekly sample through day 21.
  • Four of 6 cats had increased titers on day 28 compared to day 21.
  • One cat had died of FIP prior to day
  • Experiment 85-02 - Living 21st passage 79- 1146 The control cats (Group A) from experiment 85-01 were utilized to screen the virulence of the 21st passage of virus (9 low temperature passages). Four of these cats were divided into 2 groups of 2 cats each. One group served as unvaccinated controls, and the second group (Group D) received 1.0 ml of live 21st passage virus subcutaneously.
  • the 2 cats in group D received a single subcutaneous dose of a vaccine containing 10 6 TCID 50 of virus.
  • the 2 controls were challenged on day 28 with virulent UCD ⁇ virus. Both cats developed clinical FIP. The temperatures of these cats after challenge are listed in Table 8.
  • SUBSTITUTE SHEET The neutralizing titers of these cats after vaccination are listed in Table 9. The 2 control cats did not have neutralizing titers through day 21. The 2 cats receiving the 21st passage of live virus first had titers on day 14.
  • Kitten ME2 had a low grade febrile response on days 2, 3, 8, 18, 21, and 35, but did have a temperature of 105.2 on day 7.
  • Kitten ME3 had low grade fever on days 2, 9, 23, 28, 30, 32, and 35. Since temperatures were not recorded on every day during the secondary disease phase, kittens in all like ⁇ lihood had fever on more days than were recorded. As of the date of this report (day 54 after vaccination) , both of these cats are still alive and reasonably healthy. They are thinner than the controls and are periodically showing low grade fevers, but they are bright, alert, and continue to eat.
  • Experiment 85-04 Comparison of 40th passage of FIPV 79-1146 attenuated live virus with the 6th passage of FIPV-Cornell-1: Fourteen 14-week-old Liberty Lab SPF kittens were divided into 4 groups of 2 kittens each as outlined in Table 10.
  • Group A was the nonvaccinated control
  • Groups B and C received attenuated live virus intranasally and subcutaneously (1.0 ml/kitten of a 1:3,000 dilution of 40th passage of virus, or 10 4 TCID 50 /kitten) .
  • Group G kittens received 1.0 ml (10 TCID ⁇ Q ) subcutaneously of the 6th passage of the Cornell-1 (CU-1) isolate of FIPV.
  • SUBSTITUTE SHEET were Liberty Lab cats that had been uninoculated controls in a previous experiment and did not have antibodies to FIPV.
  • the other 2 cats (73, 52) were control cats from another experiment, had come from a colony where most every kitten seroconverted to feline coronaviruses, and these seropositive cats were sensitized to challenge with FIPV-UCD ⁇
  • Vaccine FIPV-1146 Passage 19 ( Dilute 3 .5 ml stock vi Each vaccinate received 0.5 ml or 100,000 TCID ⁇ Q
  • VN antibody titers weekly.
  • HG4 21 3.4 4.4 3.8 ND ND ND n Mean 3.5 4.0 3.7 ND ND ND
  • the s tarting ( plaque purif ied 11th passage) virus WSU FIPV 79-1146 (also referred to as FIPV 79-1146 or 79-1146) has been deposited with the ATCC and has been ass igned access No . VR 2125.
  • SUBSTITUTE SHEET The 19th passage virus has been deposited with the ATCC and has been assigned accession No. VR 2126.
  • the 40th passage virus has been deposited with the ATCC and has been assigned accession No. VR 2127.
  • the 50th passage virus has been deposited with the ATCC and has been assigned accession No. VR 2128.

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  • 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)
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  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

On a découvert que le virus de la péritonite infectieuse des félins, WSU FIPV 79-1146, peut être affaibli pour former un vaccin vivant modifié contre la péritonite infectieuse des félins (PIF), qui transmet l'immunité, est sûr et ne provoque pas la PIF, chez le félin.
PCT/US1987/000216 1986-02-06 1987-02-05 Vaccin contre la peritonite infectieuse des felins WO1987004624A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1019880700238A KR950002983B1 (ko) 1986-07-03 1987-06-18 롤러를 구비한 유체동력 장치

Applications Claiming Priority (2)

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US82663886A 1986-02-06 1986-02-06
US826,638 1986-02-06

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WO1987004624A1 true WO1987004624A1 (fr) 1987-08-13

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PCT/US1987/000216 WO1987004624A1 (fr) 1986-02-06 1987-02-05 Vaccin contre la peritonite infectieuse des felins

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EP (1) EP0261168A1 (fr)
JP (1) JPS63502828A (fr)
AU (1) AU604682B2 (fr)
CA (1) CA1303500C (fr)
WO (1) WO1987004624A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0310362A2 (fr) * 1987-10-01 1989-04-05 Norden Laboratories, Inc. Vaccin pour la protection des chats contre la péritonite infectieuse féline
US5667785A (en) * 1987-10-01 1997-09-16 Pfizer Inc. Vaccine for protection of cats against feline infectious peritonitis
US5811104A (en) * 1988-12-30 1998-09-22 American Home Products Corporation Recombinant structural and non-structural proteins of FIPV and method of immunizing
WO1999039733A1 (fr) * 1998-02-04 1999-08-12 Heska Corporation Methode d'administration de poxvirus recombine de raton laveur
US6033845A (en) * 1996-12-18 2000-03-07 Engene Biotechnologies Inc Specific diagnostic for feline infectious peritonitis antibodies
US6280974B1 (en) 1990-11-14 2001-08-28 Pfizer Inc Recombinant feline coronavirus S proteins
CN116042538A (zh) * 2022-11-24 2023-05-02 华中农业大学 一株猫冠状病毒及其应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4021302A (en) * 1966-02-18 1977-05-03 Burroughs Wellcome & Co., Inc. Cell cultures
US4195130A (en) * 1978-04-20 1980-03-25 Cornell Research Foundation, Inc. Propagation of feline infectious peritonitis virus in tissue cultures
EP0011864A1 (fr) * 1978-11-30 1980-06-11 The Wellcome Foundation Limited Souche atténuée du virus de la péritonite infectieuse des félins, procédé pour sa préparation et vaccin la contenant
EP0027347A1 (fr) * 1979-10-16 1981-04-22 Norden Laboratories, Inc. Virus de la péritonite infectieuse des félins, sa préparation et vaccins le contenant

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE1044T1 (de) * 1978-11-30 1982-06-15 The Wellcome Foundation Limited Impfstoff gegen infektioese peritonitis der feliden und verfahren zu seiner herstellung.

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4021302A (en) * 1966-02-18 1977-05-03 Burroughs Wellcome & Co., Inc. Cell cultures
US4195130A (en) * 1978-04-20 1980-03-25 Cornell Research Foundation, Inc. Propagation of feline infectious peritonitis virus in tissue cultures
EP0011864A1 (fr) * 1978-11-30 1980-06-11 The Wellcome Foundation Limited Souche atténuée du virus de la péritonite infectieuse des félins, procédé pour sa préparation et vaccin la contenant
EP0027347A1 (fr) * 1979-10-16 1981-04-22 Norden Laboratories, Inc. Virus de la péritonite infectieuse des félins, sa préparation et vaccins le contenant

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Biological Abstracts, Volume 79, No. 7, 1985, (Philadelphia, Pa., US), N.C. PEDERSEN et al. : "Pathogenicity Studies of Feline Coronavirus Isolates 79-1146 and 79-1683", see Abstract No. 59641, & Am. J. Vet. Res. 45(12): 2580-2585, 1984 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0310362A2 (fr) * 1987-10-01 1989-04-05 Norden Laboratories, Inc. Vaccin pour la protection des chats contre la péritonite infectieuse féline
EP0310362A3 (en) * 1987-10-01 1990-03-21 Norden Laboratories, Inc. Vaccine for protection of cats against feline infectious peritonitis
AU620819B2 (en) * 1987-10-01 1992-02-27 Pfizer Inc. Vaccine for protection of cats against feline infectious peritonitis
US5667785A (en) * 1987-10-01 1997-09-16 Pfizer Inc. Vaccine for protection of cats against feline infectious peritonitis
US5811104A (en) * 1988-12-30 1998-09-22 American Home Products Corporation Recombinant structural and non-structural proteins of FIPV and method of immunizing
US6280974B1 (en) 1990-11-14 2001-08-28 Pfizer Inc Recombinant feline coronavirus S proteins
US6642359B2 (en) 1990-11-14 2003-11-04 Pfizer Inc. Recombinant feline coronavirus S proteins
US6033845A (en) * 1996-12-18 2000-03-07 Engene Biotechnologies Inc Specific diagnostic for feline infectious peritonitis antibodies
WO1999039733A1 (fr) * 1998-02-04 1999-08-12 Heska Corporation Methode d'administration de poxvirus recombine de raton laveur
US6106841A (en) * 1998-02-04 2000-08-22 Heska Corporation Delivery method for recombinant raccoon poxvirus
CN116042538A (zh) * 2022-11-24 2023-05-02 华中农业大学 一株猫冠状病毒及其应用
CN116042538B (zh) * 2022-11-24 2024-05-07 华中农业大学 一株猫冠状病毒及其应用

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AU7037287A (en) 1987-08-25
CA1303500C (fr) 1992-06-16
EP0261168A1 (fr) 1988-03-30
JPS63502828A (ja) 1988-10-20
AU604682B2 (en) 1991-01-03

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