CN86100726A - 制造犬细小病毒疫苗的方法 - Google Patents
制造犬细小病毒疫苗的方法 Download PDFInfo
- Publication number
- CN86100726A CN86100726A CN86100726.3A CN86100726A CN86100726A CN 86100726 A CN86100726 A CN 86100726A CN 86100726 A CN86100726 A CN 86100726A CN 86100726 A CN86100726 A CN 86100726A
- Authority
- CN
- China
- Prior art keywords
- virus
- vaccine
- strain
- canine parvovirus
- cell
- 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.)
- Granted
Links
- 229960005486 vaccine Drugs 0.000 title claims abstract description 45
- 241000701931 Canine parvovirus Species 0.000 title claims abstract description 42
- 238000000034 method Methods 0.000 title claims abstract description 20
- 241000700605 Viruses Species 0.000 claims description 34
- 241000282465 Canis Species 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000003381 stabilizer Substances 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 4
- 102000004169 proteins and genes Human genes 0.000 claims description 4
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 2
- 241000711506 Canine coronavirus Species 0.000 claims description 2
- 241000712079 Measles morbillivirus Species 0.000 claims description 2
- 241000711798 Rabies lyssavirus Species 0.000 claims description 2
- 230000036760 body temperature Effects 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 230000001717 pathogenic effect Effects 0.000 claims description 2
- 101150104494 CAV1 gene Proteins 0.000 claims 1
- 101150047856 Cav2 gene Proteins 0.000 claims 1
- 241001215120 Leptospirales Species 0.000 claims 1
- 206010037660 Pyrexia Diseases 0.000 claims 1
- 125000000837 carbohydrate group Chemical group 0.000 claims 1
- 239000007857 degradation product Substances 0.000 claims 1
- 241000712461 unidentified influenza virus Species 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 241000282472 Canis lupus familiaris Species 0.000 description 22
- 238000002255 vaccination Methods 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 17
- 238000004113 cell culture Methods 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000008774 maternal effect Effects 0.000 description 9
- 208000015181 infectious disease Diseases 0.000 description 7
- 238000011081 inoculation Methods 0.000 description 7
- 241000282326 Felis catus Species 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000000405 serological effect Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 241000701915 Feline panleukopenia virus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000009849 deactivation Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 208000000655 Distemper Diseases 0.000 description 2
- 241000282323 Felidae Species 0.000 description 2
- 208000002613 Feline Panleukopenia Diseases 0.000 description 2
- 208000008071 Parvoviridae Infections Diseases 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- VEZXCJBBBCKRPI-UHFFFAOYSA-N beta-propiolactone Chemical compound O=C1CCO1 VEZXCJBBBCKRPI-UHFFFAOYSA-N 0.000 description 2
- 210000003969 blast cell Anatomy 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 230000003067 hemagglutinative effect Effects 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 229960000380 propiolactone Drugs 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 230000001018 virulence Effects 0.000 description 2
- PSBDWGZCVUAZQS-UHFFFAOYSA-N (dimethylsulfonio)acetate Chemical class C[S+](C)CC([O-])=O PSBDWGZCVUAZQS-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 241000588807 Bordetella Species 0.000 description 1
- 241000712083 Canine morbillivirus Species 0.000 description 1
- 102100035888 Caveolin-1 Human genes 0.000 description 1
- 102100038909 Caveolin-2 Human genes 0.000 description 1
- 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 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 208000037319 Hepatitis infectious Diseases 0.000 description 1
- 101000715467 Homo sapiens Caveolin-1 Proteins 0.000 description 1
- 101000740981 Homo sapiens Caveolin-2 Proteins 0.000 description 1
- 206010024238 Leptospirosis Diseases 0.000 description 1
- 206010025327 Lymphopenia Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 206010057343 Parvovirus infection Diseases 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 201000009840 acute diarrhea Diseases 0.000 description 1
- 230000000240 adjuvant effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 229910000318 alkali metal phosphate Inorganic materials 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 229940001007 aluminium phosphate Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229940031567 attenuated vaccine Drugs 0.000 description 1
- 230000000680 avirulence Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 244000144987 brood Species 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 239000012930 cell culture fluid Substances 0.000 description 1
- RLGQACBPNDBWTB-UHFFFAOYSA-N cetyltrimethylammonium ion Chemical class CCCCCCCCCCCCCCCC[N+](C)(C)C RLGQACBPNDBWTB-UHFFFAOYSA-N 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000009264 composting Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 229940031551 inactivated vaccine Drugs 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000000937 inactivator Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000001739 intranuclear inclusion body Anatomy 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 231100001023 lymphopenia Toxicity 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 102220055615 rs144152239 Human genes 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940117986 sulfobetaine Drugs 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000005723 virus inoculator Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- 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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14311—Parvovirus, e.g. minute virus of mice
- C12N2750/14322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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
- Y10S424/818—Viral vaccine for canidae or mustelidae, e.g. dogs, foxes, minks
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Abstract
本发明涉及一种制造包含新犬细小病毒株疫苗的方法,该疫苗能突破9-12周龄幼犬中保持的从母体衍生的抗体水平,甚至可以在有母体衍生抗体存在下免疫大多数6周龄的幼犬。
Description
本发明涉及一种新的犬细小病毒疫苗,一种制备该疫苗的方法,一种新的犬细小病毒株,以及一种使犬免受犬细小病毒感染的方法。
犬特别是年青犬受到犬细小病毒(CPV)的感染,常常导致以急性腹泻、发热、白细胞减少(相对地淋巴细胞减少)为特征的肠道疾病。
虽曾研究出一种防止犬受CPV感染的痰苗。然而,当存在母体获得性抗体(MDA)时给予这些疫苗常常是无效的。对某些幼犬,这种被动免疫可能以足以妨碍疫苗接种的水平,持续相当长的时间(四个月或更长)。其后,随着MDA水平的降低,狗可能不足以对抗感染和疾病的侵袭,而仍难于接种成功。因此,在这些幼犬的生命早期的相当长时期内,仍不能得以保护;特别是在由母体获得的免疫性消失之后,整个一窝仔犬受感染的危险就显现出来了。
为此,很需要有一种对幼犬生命早期能够进行成功免疫的CPV疫苗。
本发明的目的即是制备这样一种疫苗的方法。
依据本发明而制得的疫苗,其特征在于它包含得自一种CPV病毒株(内部编号为154)的病毒。这种病毒株的样品已寄存在法国巴黎巴士德研究院的国家微生物培养物保藏中心(Colleetion Nationale de Cultures de Mieroorganisms),寄存号为1-404。
依据本发明的疫苗,最好含有活的减毒CPV病毒株。
减毒是通过在细胞的培养物中经一系列传代完成的,所用的细胞取自犬或猫科动物,传代于大约37℃下进行。每一步都是由上次培养步骤的培养物中收取病毒,之后接种到含有新鲜细胞培养物的培养基中。培养所使用的细胞是按本领域内已知的方法制备的。
为制备该疫苗,可将减毒的种株病毒培养在一细胞培养物中,如一种猫科动物的胚胎纤维母细胞(FEF)培养物。所用的培养温度最好是犬的正常体温。收集组织细胞培养液和/或细胞,以收获经培养的病毒。为了提高病毒收获率,可以使用某种提高由培养基质中释放出的传染颗粒的技术,如用超声处理。可将疫苗制成悬浮液形成或冻干品。对于冻干的CPV疫苗,最好向其中加入一种或多种稳定剂。适用的稳定剂如SPGA(详见Bovarnick(1950):J.Bacteriology 59,509)醣类(如山梨醇、甘露醇、淀粉、蔗糖、葡聚糖、葡萄糖)、蛋白质(如白蛋白或酪蛋白),或是其降解产物、含蛋白制剂(如小牛血清或脱脂奶)以及缓冲液(如碱金属磷酸盐)。必要时亦可加入一种或多种具有佐剂作用的化合物。适用的佐剂如氢氧化铝、磷酸盐或氧化物、矿物油(如BayolF,Marcol 52)以及皂角苷。
另外,依据本发明的疫苗亦可含有灭活的CPV病毒株。
依据本发明灭活的CPV疫苗,是由经处理失去了复制能力和毒力的病毒制得的。一般地,这可以通过化学或物理的方法达到。化学灭活,如可以用酶,甲醛、β-丙内酯或吖丙啶或其衍生物、某种有机溶剂(如卤化烃)和/或去污剂(如吐温、Triton X、脱氧胆酸钠、磺基三甲铵乙内酯或十六烷基三甲基铵盐)处理病毒来完成。物理灭活,可通过用高能射线对病毒进行照射来完成,如可使用紫外光,r射线或x射线。必要时,处理后可将灭活剂中和掉,例如可用硫代硫酸盐来中和甲醛灭活制剂。如有必要,继后亦可将PH值调回大约PH7。一般地,可向灭活病毒制品中加入某种佐剂,并且可加入一种或几种乳化剂(如吐温和斯潘(TWeen和Span))。
依据下列特征,将该病毒株154鉴定为犬细小病毒:
(ⅰ)在猫科或犬科动物细胞内有繁殖能力。
(ⅱ)不能在没有分裂能力的猫科和犬科动物细胞中繁殖。
(ⅲ)细胞培养物中所产生的血凝素在PH7.2时可使猪红细胞凝集,但不能使人类或啮齿动物的红细胞凝集。
(ⅳ)在细胞培养物中产生典型的核内含体。
(ⅴ)它可被制备的猫和兔的抗猫传染性粒细胞缺乏症(猫瘟)病毒和已知的犬细小病毒抗血清所中和。
(ⅵ)血凝作用可被抗猫传染性粒细胞缺乏症(猫瘟)病毒和已知的犬细小病毒抗血清所抑制。
此外,根据下列特性可将该新的CPV病毒株同迄今已知的CPV病毒株进一步区分开:
a.它能够于37℃,在猫和犬的纤维母细胞样细胞中生长繁殖良好,并表现出特征性的细胞病理效力。将依据本发明的病毒株与已知的CPV病毒株相比较,总结出其生长特征,如下面表1所示:
表Ⅰ
不同的CPV病毒株在不同的细胞培养系统中生长繁殖的能力
所使用的
细胞培养物 A72 FEF CRFK
CPV病毒株
Boostervac(C-Vet) - ++++ +++
Enduracell(Smith-kline) + - +
Nobivac P、C. ++++ ++ +++
野生型 +++ +++ +++
说明:
A72=Binn氏犬纤维母细胞系
FEF=猫胚胎纤维母细胞系
CRFK=克兰达尔猫肾细胞系
++++=于第一代即有广泛的细胞病理效力(CPE)和血凝作用(HA)
+++=于第一代有轻度CPE
++=到第二代时表现CPE和HA
+=第二代后产生CPE
-=反复传代后亦未见CPE和HA
b.于上述的细胞系中培养时,在琼脂下面产生大的、清晰的噬斑。
根据上述资料,可以得出CPV病毒株154代表了一株新的病毒株的结论。
病毒株154是由表现有CPV感染症状的幼犬的粪便中得到的。但也可由病毒感染幼犬或成年犬的肠道、胸腺或其它淋巴样组织、骨髓、血液或肝组织中分离。可用缓冲盐水或细胞培养基纯化并稀释分离的样品材料,之后接种于狗或猫的分裂活跃的细胞上。
与含有已知病毒株的疫苗相反,依据本发明的疫苗,对于大部分6周令的幼犬,以及事实上100%的9-12周令的幼犬是有效的,这种新的CPV病毒能够使接种了疫苗的幼小犬打破事实上存在的来自母体抗体的对抗性,而不引起CPV感染的症状。
12周时,母体抗体滴度通常降低到1∶32以下,且在12周时母体抗体水平很少超过1∶32。几乎100%的滴度水平为1∶32的动物,均能对依据本发明之疫苗的予防接种产生反应,甚至滴度水平为1∶64的大部分幼犬也能产生反应。
使用活的减毒疫苗,推荐的剂量为每只幼犬103TCID50以上,但对于有MDA的幼犬,最好每只动物至少给106TCID50。
这些疫苗可经非肠道途径(即注射)或肠道途径(即口服)给药。
本发明的疫苗还包括除上述CPV疫苗病毒以外的联合疫苗,其至少包含下列犬疫苗病毒之一种:犬温热病毒、犬传染性肝炎病毒(CAV1和CAV2)、狂犬病病毒、副流感病毒、犬冠状病毒、麻疹病毒,和/或感染性钩端螺旋体病病菌及博代杆菌(Bordetella)。
为了试验传播期间CPV的病源性、免疫源性和有无毒力增强,将CPV相继传给7只犬。在这项研究中使用了18只幼犬,在接触时所有的均没有抗体。整个观察期间所有幼犬的存活,并证明了有抗体反应。白细胞计数在正常范围之内。
为了证明使用本发明之疫苗进行疫苗接种所产生的保护效果,四只疫苗接种6周显示有抗体反应的幼犬,同两只未作疫苗接种的对照犬,接触有毒力的CPV病毒株。结果未作疫苗接种的犬出现了有CPV感染特征的临床征象,而作过疫苗接种的幼犬则没有出现这种征象。
实施例1
病毒的分离和传代
用拭子采取有细小病毒感染的临床病例的直肠内标本,之后由其上分离病毒。该感染犬系狗窝内喂养的8周令比哥猎犬幼犬。
将病毒接种到FEF细胞培养物中,并在这些细胞中进一步传代,之后转移到犬A72细胞系培养物内〔Binn、MarchWicki & Stephenson A.M.J.V.R..41卷,855-860页(1981)〕。病毒在细胞培养物中的所有传代均于37℃进行。
在该细胞系中对病毒进行相继41次传代以减毒,在传代过程中,分别于第4、第7、第10和第40代完成4次克隆步骤。每次都收集到一个大而清晰的弧立的噬斑。
之后将存在于A72细胞(POOL182)中的第41代病毒重新接种FEF培养物中,收获在FEF(POOL182)细胞中的第二代病毒,以其作为“主体种子”堆铺层,并定名为POOL190。
实施例2
活疫苗的制备
A.由按照实施例1方法得到的主体种子病毒堆制备初级和二级工作种子病毒堆。这些病毒是由A72细胞系转染后的4和5次FEF细胞培养物传代。将FEF细胞培养物用工作种子病毒感染,以接种。孵育该培养物,直到病毒的细胞病理效应达到适当的程度。此时收获细胞培养的培养基并于-70℃储存。
B.分析收获物样品的病毒滴度并试验其有无细菌混染。已知其病毒滴度后,将其与稳定剂混合,达到在制成的混合物中含5.5%山梨醇和5.5% NZ胺(一种酪蛋白的胰酶消化产物)。之后将该混合物装入中性玻璃瓶(体积为1.0毫升)中,再予以冻干并于真空下封口。
实施例3
对尚存在母体抗体的幼犬的疫苗接种
取135只经用血凝抑制方法证明其体内含有不同水平母体来源之抗体(MDV)的幼犬,每只均给予CPA剂量为107.4TCID50的疫苗。其中124只是6周令时作疫苗接种,其余的11只是在9周令时接种。小部分6周令的幼犬没有对疫苗接种产生血清学反应,对这些动物在其8-9周令的再次接种,且在所有这些疫苗接种条件下,动物均表现了及时的血清转化反应。
表2和表3中显示对这些结果的总结。
表2
一次疫苗接种之幼犬的血清学反应
6周时 幼犬的 所试验 6周时 6周时 9周 9周时
MDA的 数目 的幼犬 作疫苗 疫苗接 时作 疫苗接
滴度 占总数 接种的 种后出 疫苗 种后出
的百分 数目 现血清学 接种 现血清
比(%) 反应数 的数 学反应
目(%) 目 数目%
20 16 12 12 10 83 4 4 100
20 18 13 16 15 94 2 2 100
40 51 38 50 44 88 1 1 100
80 39 29 37 26 70 2 2 100
160 11 8 9 7 78 2 2 100
135 124 102 82 11 11 100
(平均) (平均)
表3
6周令时疫苗接种没有出现反应的幼犬于
8-9周时再次疫苗接种的血清学反应
6周时的 8-9周时再次 血清学反应
MDA滴 疫苗接种的幼 数目 %
度 犬数
20 2 2 100
20 1 1 100
40 6 6 100
80 11 11 100
160 2 2 100
22 22 100
实施例4
存在有可测到的母体得到之抗体时,用其它疫苗进行接种之效力的比较
通过两次分别进行的实验,对三种不同的疫苗的效力进行了比较。
第一组实验是用Smith-Klines氏活减毒CPV疫苗(SK-CPV)或Intervet猫细小病毒疫苗(FLV)对比哥猎犬群体中的青年犬进行疫苗接种。
第二组实验是用依据本发明的活的CPV疫苗(Int-CPV)或Intervet猫细小病毒疫苗(FLV)对比哥猎犬群体中的幼犬进行疫苗接种。
幼犬从其4-8周令开始每周进行疫苗接种。所有幼犬均由其母体获得了母体抗体。
实验结果如表4所示。
表4
第一组实验 第二组实验
SK-CPV FLV Int-CPV FLV
处理的仔犬窝数 27 38 16 16
生存的幼犬数 156 212 108 91
断奶并疫苗接种的 136 194 99 84
幼犬数
因CPV感染致断
奶后死亡数 15 21 4 11
因CPV感染致死
的%数 11.0 10.8 4 13.1
患病幼犬治疗后恢
复数, 24 35 2 18
显示临床CPV
病征的总的%数 28.7 28.9 6 34.5
由此可以得出结论:用根据本发明的疫苗对幼犬进行免疫,其对抗致命的CPV病的作用远优于用已知疫苗所得到的防护。
实施例5
灭活疫苗的制备
将按照实施例2的方法制得的细胞培养基(每毫升滴度为10/8 tcid/50)于37℃培养2小时,此期间用浓度为0.1%的β-丙内酯处理。
逐滴加入1N NaOH间断将大部分流体中和。如需要调节pH时,可用加在培养介质中的酚红作指示剂。
最后将作为佐剂的磷酸铝同该混合物相混合,达到终浓度为0.3%。
实施例6
母体免疫的幼犬12周令时疫苗接种的反应
用依据实施例2的方法制备的活疫苗,或者用基于猫病毒的异型疫苗,免疫显示有很高母体抗体滴度的两组幼犬。
用血凝抑制滴定法检测母体抗体。
各组动物均给于三个不同剂量的疫苗,每组包括9只幼犬。
结果如表5所示。
表5
组Ⅰ:Nobivac PC
剂量/幼犬 犬号 接种时MDA 反应
(tcid/50) (HI滴度)
10/6 1 16 无
2 32 无
3 16 有
4 16 有
10/7 5 8 有
6 32 有
7 16 有
10/8 8 32 有
9 32 有
组Ⅱ:猫细小病毒
10 16 无
10/6 11 16 无
12 8 无
13 16 无
10/7 14 8 无
15 16 无
16 8 无
10/8 17 4 无
18 8 无
Claims (7)
1、犬细小病毒株154。
2、根据权利要求1所述病毒株,它贮存在武汉大学内的中国典型培养物贮存中心,贮存号为CCTCC-V86001。
3、制备犬细小病毒疫苗的方法,其特征在于将犬细小病毒株154接种到犬或猫科动物细胞中,经数代培养减毒,再在FEF细胞中培养收集病毒,再加一种或多种药物学允许的稳定剂或(和)其他佐剂制成。
4、根据权利要求3的方法,其特征在于犬细小病毒株在FEF细胞中传41代减毒,在FEF中培养温度为犬正常体温。
5、根据权利要求3或4的方法,其特征在于所加稳定剂为糖类,蛋白质或是其降解物,含蛋白制剂以及缓冲液。
6、根据权利要求3或4的方法,其特征在于其病毒株是贮存在武汉大学内的中国典型培养物贮存中心的犬细小病毒株154,贮存号为CCTCC-V86001。
7、制备联合疫苗的方法,其特征在于它除含用权利要求2方法制得的疫苗病毒外,还至少含有下列疫苗病毒中的一种:犬热病病毒、传染性犬肝炎病毒(CAV-1和CAV-2),狂犬病病毒、付流感病毒、犬冠状病毒、麻疹病毒和/或致病菌-钓端螺旋体和博代杆菌。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB858502399A GB8502399D0 (en) | 1985-01-31 | 1985-01-31 | Canine parvovirus vaccines |
GB8502399 | 1985-01-31 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN86100726A true CN86100726A (zh) | 1986-10-01 |
CN1022801C CN1022801C (zh) | 1993-11-24 |
Family
ID=10573707
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN86100726A Expired - Lifetime CN1022801C (zh) | 1985-01-31 | 1986-01-29 | 制造犬细小病毒疫苗的方法 |
Country Status (16)
Country | Link |
---|---|
US (2) | US4810494A (zh) |
EP (1) | EP0189958B1 (zh) |
JP (1) | JPH07112982B2 (zh) |
CN (1) | CN1022801C (zh) |
AT (1) | ATE47524T1 (zh) |
AU (1) | AU592786B2 (zh) |
CA (1) | CA1278513C (zh) |
DE (1) | DE3666529D1 (zh) |
DK (1) | DK162421C (zh) |
ES (1) | ES8706030A1 (zh) |
FI (1) | FI85222C (zh) |
GB (1) | GB8502399D0 (zh) |
IE (1) | IE58357B1 (zh) |
IL (1) | IL77694A (zh) |
NZ (1) | NZ214984A (zh) |
ZA (1) | ZA86446B (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101942419A (zh) * | 2010-07-30 | 2011-01-12 | 中国农业科学院哈尔滨兽医研究所 | 犬细小病毒弱毒疫苗株及其应用 |
CN106591242A (zh) * | 2016-11-18 | 2017-04-26 | 北京世纪元亨动物防疫技术有限公司 | 一株犬细小病毒毒株cpv‑yh及其应用 |
CN110859956A (zh) * | 2019-11-07 | 2020-03-06 | 衡阳师范学院 | 一种犬细小病毒灭活疫苗及其制备方法 |
CN117106732A (zh) * | 2023-09-07 | 2023-11-24 | 华中农业大学 | 一株犬细小病毒及其应用 |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8502399D0 (en) * | 1985-01-31 | 1985-03-06 | Akzo Nv | Canine parvovirus vaccines |
IE66015B1 (en) * | 1987-09-28 | 1995-11-29 | Beecham Inc | TGEV-virus of swine as a dog vaccine |
AU633349B2 (en) * | 1989-08-08 | 1993-01-28 | Fort Dodge Australia Pty Limited | Attenuated canine parvovirus (cpv), vaccine comprising cpv and method of preventing infection by cpv in dogs |
DE69023140T2 (de) * | 1989-08-08 | 1996-03-21 | Webster Arthur Pty Ltd | Attenuiertes hundeparvovirus (cpv), cpv enthaltender impfstoff und verfahren zur verhütung von infektionen durch cpv bei hunden. |
US5814510A (en) * | 1994-11-08 | 1998-09-29 | Cornell Research Foundation, Inc. | Attenuated canine parvovirus vaccine |
US5885585A (en) * | 1994-11-08 | 1999-03-23 | Cornell Research Foundation, Inc. | Attenuated canine parvovirus vaccine |
US6063385A (en) * | 1997-11-07 | 2000-05-16 | Wisconsin Alumni Research Foundation | DNA vaccine for parvovirus |
ATE395077T1 (de) * | 2003-01-29 | 2008-05-15 | Pfizer Prod Inc | Hundeimpfstoffe gegen bordetella bronchiseptica |
US8802171B2 (en) * | 2004-05-25 | 2014-08-12 | James B. Watson | Live organism product |
US20050266027A1 (en) * | 2004-05-25 | 2005-12-01 | Watson James B | Live organism product |
US8052971B2 (en) * | 2005-11-21 | 2011-11-08 | MG Biologics | Oral use of specific antibodies for intestinal health |
US7682619B2 (en) | 2006-04-06 | 2010-03-23 | Cornell Research Foundation, Inc. | Canine influenza virus |
NZ582019A (en) * | 2007-06-14 | 2012-07-27 | Univ Oklahoma State | Vaccines containing canine parvovirus genetic variants |
US8227583B2 (en) * | 2007-06-14 | 2012-07-24 | The Board Of Regents For Oklahoma State University | Vaccines containing canine parvovirus genetic variants |
WO2011107534A1 (en) * | 2010-03-05 | 2011-09-09 | Intervet International B.V. | Recombinant attenuated parvovirus |
WO2012164372A1 (en) | 2011-06-01 | 2012-12-06 | Indian Immunologicals Limited | Recombinant anti-canine parvovirus antibody and uses thereof |
CN109735505A (zh) * | 2018-12-26 | 2019-05-10 | 河南农业大学 | 一株犬细小病毒毒株及其基因序列的扩增和应用 |
CN113073083B (zh) * | 2020-01-03 | 2022-09-06 | 普莱柯生物工程股份有限公司 | 犬细小病毒弱毒株、及其制备的疫苗组合物和应用 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4193991A (en) * | 1978-12-20 | 1980-03-18 | Cornell Research Foundation, Inc. | Canine parvovirus vaccine |
US4303645A (en) * | 1980-04-18 | 1981-12-01 | Cornell Research Foundation, Inc. | Modified living canine parvovirus vaccine |
EP0117767A1 (en) * | 1983-01-07 | 1984-09-05 | Mgi Pharma, Inc. | Production of parvovirus subunit vaccines |
GB8502399D0 (en) * | 1985-01-31 | 1985-03-06 | Akzo Nv | Canine parvovirus vaccines |
-
1985
- 1985-01-31 GB GB858502399A patent/GB8502399D0/en active Pending
-
1986
- 1986-01-20 IE IE16886A patent/IE58357B1/en not_active IP Right Cessation
- 1986-01-21 AT AT86200088T patent/ATE47524T1/de not_active IP Right Cessation
- 1986-01-21 ZA ZA86446A patent/ZA86446B/xx unknown
- 1986-01-21 EP EP86200088A patent/EP0189958B1/en not_active Expired
- 1986-01-21 DE DE8686200088T patent/DE3666529D1/de not_active Expired
- 1986-01-23 IL IL77694A patent/IL77694A/xx not_active IP Right Cessation
- 1986-01-23 CA CA000500153A patent/CA1278513C/en not_active Expired - Lifetime
- 1986-01-28 US US06/823,333 patent/US4810494A/en not_active Expired - Lifetime
- 1986-01-29 CN CN86100726A patent/CN1022801C/zh not_active Expired - Lifetime
- 1986-01-29 AU AU52801/86A patent/AU592786B2/en not_active Expired
- 1986-01-30 NZ NZ214984A patent/NZ214984A/en unknown
- 1986-01-30 JP JP61019162A patent/JPH07112982B2/ja not_active Expired - Fee Related
- 1986-01-30 FI FI860445A patent/FI85222C/fi not_active IP Right Cessation
- 1986-01-30 DK DK047286A patent/DK162421C/da not_active IP Right Cessation
- 1986-01-30 ES ES551461A patent/ES8706030A1/es not_active Expired
-
1993
- 1993-02-25 US US08/025,713 patent/US5316764A/en not_active Expired - Lifetime
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101942419A (zh) * | 2010-07-30 | 2011-01-12 | 中国农业科学院哈尔滨兽医研究所 | 犬细小病毒弱毒疫苗株及其应用 |
CN106591242A (zh) * | 2016-11-18 | 2017-04-26 | 北京世纪元亨动物防疫技术有限公司 | 一株犬细小病毒毒株cpv‑yh及其应用 |
CN106591242B (zh) * | 2016-11-18 | 2019-08-30 | 北京世纪元亨动物防疫技术有限公司 | 一株犬细小病毒毒株cpv-yh及其应用 |
CN110859956A (zh) * | 2019-11-07 | 2020-03-06 | 衡阳师范学院 | 一种犬细小病毒灭活疫苗及其制备方法 |
CN117106732A (zh) * | 2023-09-07 | 2023-11-24 | 华中农业大学 | 一株犬细小病毒及其应用 |
CN117106732B (zh) * | 2023-09-07 | 2024-02-06 | 华中农业大学 | 一株犬细小病毒及其应用 |
Also Published As
Publication number | Publication date |
---|---|
IE58357B1 (en) | 1993-09-08 |
EP0189958B1 (en) | 1989-10-25 |
FI860445A (fi) | 1986-08-01 |
ZA86446B (en) | 1986-09-24 |
JPH07112982B2 (ja) | 1995-12-06 |
EP0189958A3 (en) | 1988-07-06 |
ES8706030A1 (es) | 1987-06-01 |
FI860445A0 (fi) | 1986-01-30 |
DK47286A (da) | 1986-08-01 |
JPS61180724A (ja) | 1986-08-13 |
DK47286D0 (da) | 1986-01-30 |
DE3666529D1 (en) | 1989-11-30 |
ES551461A0 (es) | 1987-06-01 |
CN1022801C (zh) | 1993-11-24 |
NZ214984A (en) | 1988-05-30 |
DK162421C (da) | 1992-03-23 |
US4810494A (en) | 1989-03-07 |
ATE47524T1 (de) | 1989-11-15 |
IE860168L (en) | 1986-07-31 |
AU592786B2 (en) | 1990-01-25 |
AU5280186A (en) | 1986-08-07 |
CA1278513C (en) | 1991-01-02 |
IL77694A (en) | 1992-06-21 |
FI85222C (fi) | 1992-03-25 |
FI85222B (fi) | 1991-12-13 |
GB8502399D0 (en) | 1985-03-06 |
US5316764A (en) | 1994-05-31 |
EP0189958A2 (en) | 1986-08-06 |
DK162421B (da) | 1991-10-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1022801C (zh) | 制造犬细小病毒疫苗的方法 | |
EP0352835B1 (en) | IBDV production in continuous cell lines | |
KR100796871B1 (ko) | 바쿨로바이러스 벡터 발현계에서의 단백질 발현방법 | |
Evermann et al. | Biological and pathological consequences of feline infectious peritonitis virus infection in the cheetah | |
US4193991A (en) | Canine parvovirus vaccine | |
CN1275084A (zh) | 重组的猪腺病毒载体 | |
CN1052896A (zh) | 重组火鸡疱疹病毒及其衍生的活载体疫苗 | |
KR102132730B1 (ko) | 구제역 바이러스 유사 입자 백신 및 그 제조방법 | |
CN1050302C (zh) | 鸡贫血病因子疫苗 | |
US7244432B2 (en) | Infectious bursal disease virus (IBDV) variant from Georgia | |
EP0023922B1 (en) | Heterotypic canine parvovirus vaccine | |
CN101730544B (zh) | Pitman moore狂犬病病毒株对原代鸡胚成纤维细胞培养物的适应方法 | |
CN108018261B (zh) | 犬副流感病毒毒株及其应用 | |
CN113502275A (zh) | 猪伪狂犬病变异病毒毒株及其应用 | |
CN110331135A (zh) | 表达基因vii型新城疫病毒融合蛋白的重组火鸡疱疹病毒候选疫苗株及制备方法 | |
CN1155710C (zh) | 使用gB基因启动子的重组疱疹病毒 | |
CN1225553C (zh) | 表达猪细小病毒vp2基因的重组伪狂犬病毒及疫苗与制备方法 | |
CN1688335A (zh) | 生产疫苗的连续细胞系 | |
CN1258596C (zh) | 基于野兔痘的载体疫苗 | |
CN116390753A (zh) | 犬细小病毒 | |
CN112807424A (zh) | 牛病毒性腹泻、牛传染性鼻气管炎二联活疫苗及其制备方法 | |
CN1053642A (zh) | 传染性支气管炎病毒疫苗 | |
CN1679931A (zh) | 在韩国分离的犬瘟热病毒和使用该病毒的重组疫苗 | |
EP0396193A1 (en) | Canine corona virus vaccine | |
CN1781553A (zh) | H5n1亚型禽流感病毒基因工程亚单位疫苗及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
C17 | Cessation of patent right |