CN114028554B - 一种红色红球菌免疫增强剂及其在禽用疫苗中的应用 - Google Patents
一种红色红球菌免疫增强剂及其在禽用疫苗中的应用 Download PDFInfo
- Publication number
- CN114028554B CN114028554B CN202111196852.9A CN202111196852A CN114028554B CN 114028554 B CN114028554 B CN 114028554B CN 202111196852 A CN202111196852 A CN 202111196852A CN 114028554 B CN114028554 B CN 114028554B
- Authority
- CN
- China
- Prior art keywords
- immunopotentiator
- rhodococcus
- rhodococcus erythropolis
- vaccine
- poultry
- 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.)
- Active
Links
- 230000000091 immunopotentiator Effects 0.000 title claims abstract description 75
- 229960005486 vaccine Drugs 0.000 title claims abstract description 61
- 241000187561 Rhodococcus erythropolis Species 0.000 title claims abstract description 58
- 244000144977 poultry Species 0.000 title claims abstract description 43
- 241000316848 Rhodococcus <scale insect> Species 0.000 claims abstract description 32
- 238000000855 fermentation Methods 0.000 claims abstract description 22
- 230000004151 fermentation Effects 0.000 claims abstract description 22
- 238000002360 preparation method Methods 0.000 claims abstract description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims abstract description 20
- 239000012752 auxiliary agent Substances 0.000 claims abstract description 16
- 239000001963 growth medium Substances 0.000 claims abstract description 13
- 239000000843 powder Substances 0.000 claims abstract description 13
- 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 claims abstract description 10
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims abstract description 10
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims abstract description 10
- 239000008103 glucose Substances 0.000 claims abstract description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims abstract description 10
- 235000019341 magnesium sulphate Nutrition 0.000 claims abstract description 10
- 239000008213 purified water Substances 0.000 claims abstract description 10
- 239000012137 tryptone Substances 0.000 claims abstract description 10
- 230000000415 inactivating effect Effects 0.000 claims abstract description 6
- 238000012258 culturing Methods 0.000 claims abstract description 4
- 229940031551 inactivated vaccine Drugs 0.000 claims description 34
- 239000000839 emulsion Substances 0.000 claims description 33
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 30
- 239000000427 antigen Substances 0.000 claims description 29
- 108091007433 antigens Proteins 0.000 claims description 29
- 102000036639 antigens Human genes 0.000 claims description 29
- 238000012360 testing method Methods 0.000 claims description 29
- 238000001514 detection method Methods 0.000 claims description 16
- 229930182817 methionine Natural products 0.000 claims description 11
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 10
- 241001465754 Metazoa Species 0.000 claims description 10
- 235000006408 oxalic acid Nutrition 0.000 claims description 10
- 208000002979 Influenza in Birds Diseases 0.000 claims description 9
- 208000010359 Newcastle Disease Diseases 0.000 claims description 9
- 206010064097 avian influenza Diseases 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 238000004945 emulsification Methods 0.000 claims description 6
- 230000036039 immunity Effects 0.000 claims description 5
- 230000000704 physical effect Effects 0.000 claims description 5
- 230000001954 sterilising effect Effects 0.000 claims description 4
- 241000187693 Rhodococcus rhodochrous Species 0.000 claims description 3
- 238000012795 verification Methods 0.000 claims description 3
- 230000000813 microbial effect Effects 0.000 claims 1
- 235000013594 poultry meat Nutrition 0.000 description 34
- 239000003921 oil Substances 0.000 description 29
- 230000002779 inactivation Effects 0.000 description 16
- 241000287828 Gallus gallus Species 0.000 description 14
- 235000013330 chicken meat Nutrition 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 13
- 239000007788 liquid Substances 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 239000002609 medium Substances 0.000 description 10
- 150000004676 glycans Chemical class 0.000 description 9
- 229920001282 polysaccharide Polymers 0.000 description 9
- 239000005017 polysaccharide Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 238000005273 aeration Methods 0.000 description 6
- 230000003053 immunization Effects 0.000 description 6
- 238000011081 inoculation Methods 0.000 description 6
- 238000011068 loading method Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000001804 emulsifying effect Effects 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 108010039939 Cell Wall Skeleton Proteins 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000009395 breeding Methods 0.000 description 3
- 230000001488 breeding effect Effects 0.000 description 3
- 210000004520 cell wall skeleton Anatomy 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- -1 lipid compounds Chemical class 0.000 description 3
- 241000272517 Anseriformes Species 0.000 description 2
- 208000003322 Coinfection Diseases 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 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 2
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 2
- 229940063655 aluminum stearate Drugs 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940031416 bivalent vaccine Drugs 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- CVOFKRWYWCSDMA-UHFFFAOYSA-N 2-chloro-n-(2,6-diethylphenyl)-n-(methoxymethyl)acetamide;2,6-dinitro-n,n-dipropyl-4-(trifluoromethyl)aniline Chemical compound CCC1=CC=CC(CC)=C1N(COC)C(=O)CCl.CCCN(CCC)C1=C([N+]([O-])=O)C=C(C(F)(F)F)C=C1[N+]([O-])=O CVOFKRWYWCSDMA-UHFFFAOYSA-N 0.000 description 1
- 241000272525 Anas platyrhynchos Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 208000027312 Bursal disease Diseases 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000467638 Duck reovirus Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000027954 Poultry disease Diseases 0.000 description 1
- 108010009736 Protein Hydrolysates Proteins 0.000 description 1
- 208000031320 Teratogenesis Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 241000701792 avian adenovirus Species 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003640 drug residue Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011076 safety test Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- 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
- A61K39/02—Bacterial antigens
- A61K39/0208—Specific bacteria not otherwise provided for
-
- 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
- A61K39/02—Bacterial antigens
- A61K39/0241—Mollicutes, e.g. Mycoplasma, Erysipelothrix
-
- 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
- A61K39/02—Bacterial antigens
- A61K39/102—Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
- A61P31/14—Antivirals for RNA 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- 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
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/521—Bacterial cells; Fungal cells; Protozoal cells 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
- A61K2039/5252—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
- A61K2039/55—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
- A61K2039/55588—Adjuvants of undefined constitution
- A61K2039/55594—Adjuvants of undefined constitution from bacteria
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10211—Aviadenovirus, e.g. fowl adenovirus A
- C12N2710/10234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2720/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsRNA viruses
- C12N2720/00011—Details
- C12N2720/10011—Birnaviridae
- C12N2720/10034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2720/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsRNA viruses
- C12N2720/00011—Details
- C12N2720/12011—Reoviridae
- C12N2720/12211—Orthoreovirus, e.g. mammalian orthoreovirus
- C12N2720/12234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16111—Influenzavirus A, i.e. influenza A virus
- C12N2760/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18111—Avulavirus, e.g. Newcastle disease virus
- C12N2760/18134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/12011—Astroviridae
- C12N2770/12034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/20011—Coronaviridae
- C12N2770/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Microbiology (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mycology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Pulmonology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biomedical Technology (AREA)
- Dispersion Chemistry (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明属于禽用生物制品技术领域,具体涉及一种红色红球菌免疫增强剂及其在禽用疫苗中的应用。本发明的免疫增强剂为红色红球菌的培养物,所述红色红球菌的培养物的制备方法为:将红色红球菌置于添加有培养基的30L的发酵罐中培养24‑36h,高温高压灭活,即得;所述培养基包括以下组分及其质量百分数:葡萄糖1‑2%,酵母粉2‑4%,磷酸氢二钾0.01‑0.02%,硫酸镁0.4‑0.7%,胰蛋白胨3‑5%,发酵助剂0.3‑0.5%,纯化水87.78‑92.29%。本发明采用红色红球菌的培养物作为免疫增强剂制得的疫苗安全、高效,适用范围宽,抗体持续时间长。
Description
技术领域
本发明属于禽用生物制品技术领域,具体涉及一种红色红球菌免疫增强剂及其在禽用疫苗中的应用。
背景技术
随着我国养殖业规模化程度的不断提高,尤其是禽类的集约化养殖,较大的养殖密度使禽类疾病的混合感染、继发感染、并发感染层出不穷,加之免疫抑制性和免疫缺陷性疾病时有发生,为禽类疫病防控工作带来极大挑战。不可否认,在畜禽养殖过程中,抗生素的使用,促进了动物生长发育、提高了生产性能,在防治疾病、控制传染等方面发挥了巨大作用,但是,兽医临床过程中抗生素滥用、超剂量使用,使药物中毒、药物残留、致畸、致突变、耐药性等问题日益突出,甚至造成环境污染,随着生物链进入人体,严重危害人类的健康。免疫增强剂是指通过一定途径提升禽类本身机体对于抗原特异性反应抵抗能力的一种物质,其能够提升禽类本身的免疫能力。
虽然现有技术中存在多种类型的免疫增强剂应用于禽用疫苗中,但是现有的免疫增强剂存在免疫效果不佳、抗体持续时间较短等问题。
发明内容
针对现有技术的不足,本发明的目的在于提供一种红色红球菌免疫增强剂及其在禽用疫苗中的应用。本发明采用红色红球菌的培养物作为免疫增强剂,将其添加到禽用油乳剂灭活疫苗中可以明显促进疫苗诱导动物抗体的产生,且抗体持续时间长。除此之外。采用本发明免疫增强剂制得的疫苗安全、高效。
本发明的技术方案是:
一种红色红球菌免疫增强剂,所述免疫增强剂为红色红球菌的培养物,所述红色红球菌的培养物的制备方法为:将红色红球菌置于添加有培养基的30L的发酵罐中培养24-36h,高温高压灭活,即得;所述培养基包括以下组分及其质量百分数:葡萄糖1-2%,酵母粉2-4%,磷酸氢二钾0.01-0.02%,硫酸镁0.4-0.7%,胰蛋白胨3-5%,发酵助剂0.3-0.5%,纯化水87.78-92.29%。
进一步地,所述的红色红球菌免疫增强剂,所述培养基包括以下组分及其质量百分数:葡萄糖1%,酵母粉3%,磷酸氢二钾0.01%,硫酸镁0.5%,胰蛋白胨4%,发酵助剂0.4%,纯化水91.09%。
进一步地,所述发酵助剂包括草酸和蛋氨酸。
进一步地,所述草酸和蛋氨酸的质量比为2-4:10-15。
进一步地,所述草酸和蛋氨酸的质量比为3:14。
进一步地,所述培养基的pH为7.0-7.2。
进一步地,将红色红球菌置于添加有培养基的30L的发酵罐中培养的条件为:搅拌转速200r/min,通气量1:1.0、接种量6%、装液量为罐容积的70%、温度30±1℃。
进一步地,所述高温高压灭活的具体操作为121℃,101kPa,处理20min。
本发明的另一目的在于提供上述的红色红球菌免疫增强剂在制备禽用油乳剂灭活疫苗中的应用。
一种禽用油乳剂灭活疫苗,包括上述的红色红球菌免疫增强剂。
所述的红色红球菌免疫增强剂的制备方法,包括如下步骤:
S1取红色红球菌免疫增强剂,采用121℃高压蒸汽灭活30min,灭菌后待温度降至室温时,4℃保存备用;
S2将红色红球菌免疫增强剂进行定量,得定量的红色红球菌免疫增强剂;
S3将步骤S2所得定量的红色红球菌免疫增强剂按乳化配方添加至混合抗原水相中,搅拌均匀并进行常规乳化,得初始的禽用油乳剂灭活疫苗;
S4将步骤S3所得初始的禽用油乳剂灭活疫苗经物理性状检测,安全性检测、效力试验检测及商品动物免疫检测,验证合格后,即得。
进一步地,所述步骤S1中红色红球菌免疫增强剂的定量过程为:无菌移取30mL免疫增强剂样本平分到3支15mL离心管中,12000r/min高速离心5min,弃除上清液后,置于103℃干燥箱中充分干燥2小时,测定样本干物质重量。
进一步地,所述步骤S3的具体操作为:取2mg定量的红色红球菌免疫增强剂添加到抗原液中,加入5mL的Tween-80后混匀,充分混合溶解后,最终总体积为100mL,制备成抗原水相;按照抗原水相:油相=1:2比例,使用IKA T25乳化机,12000r/min高速乳化5min。
进一步地,所述步骤S3中的抗原包括禽流感H9亚型、新城疫、鸡传染性法氏囊、禽腺病毒、鸭疫李默氏杆菌、新型鸭呼肠孤。
进一步地,所述步骤S4中商品动物免疫检测是采用市购的商品鸡、鸭和鹅进行动物实验,模拟临床进行疫苗效果评估。
疫苗的安全、高效是评价其质量的重要指标,而选择合适的免疫增强剂对于疫苗的安全性和效力至关重要。本发明采用红色红球菌的培养物作为免疫增强剂,采用本发明特定的培养基制得的红色红球菌的培养物中类脂类化合物、多糖等成分含量高,能够非特异性刺激细胞免疫功能,并且可以显著促进多种细胞因子分泌,将其添加到禽用油乳剂灭活疫苗中可以明显促进疫苗诱导动物抗体的产生,且抗体持续时间长。本发明采用红色红球菌的培养物作为免疫增强剂用于禽用油乳剂灭活疫苗的制备过程,可以根据选择的抗原不同,从而使获得针对不同病毒的疫苗,适用范围宽。采用本发明红色红球菌的培养物作为免疫增强剂制得的禽用油乳剂灭活疫苗具有高度安全性,疫苗注射局部无明显残留。采用本发明免疫增强剂制得的疫苗安全、高效。
与现有技术相比,本发明具有以下优势:
(1)本发明采用红色红球菌的培养物作为免疫增强剂,通过在发酵罐中对红色红球菌进行培养,得到红色红球菌的培养物,培养过程简单,发酵时间短,有利于红色红球菌的培养物的大规模获得。
(2)将本发明所得红色红球菌的培养物作为免疫增强剂用于制备禽用油乳剂灭活疫苗,可以根据所选抗原不同,制备不同功能的疫苗,具有适用范围广,特异性强的优点。
(3)将本发明所得红色红球菌的培养物作为免疫增强剂用于制备禽用油乳剂灭活疫苗,具有高度安全性,疫苗注射局部无明显残留。除此之外,将本发明所得红色红球菌的培养物作为免疫增强剂用于制备禽用油乳剂灭活疫苗,可以明显促进疫苗诱导动物抗体的产生,且抗体持续时间长。采用本发明免疫增强剂制得的疫苗安全、高效。
具体实施方式
以下通过具体实施方式的描述对本发明作进一步说明,但这并非是对本发明的限制,本领域技术人员根据本发明的基本思想,可以做出各种修改或改进,但是只要不脱离本发明的基本思想,均在本发明的范围之内。
本发明中所用原料如无特殊说明均为市售。本发明中红色红球菌可购自广东省微生物菌种保藏中心,GDMCC No.:GDMCC 1.819。
实施例1、一种红色红球菌免疫增强剂
所述免疫增强剂为红色红球菌的培养物,所述红色红球菌的培养物的制备方法为:将红色红球菌置于添加有培养基的30L的发酵罐中培养24h,培养的条件为:搅拌转速200r/min,通气量1:1.0、接种量6%、装液量为罐容积的70%、温度30℃,高温高压灭活,所述高温高压灭活的具体操作为121℃,101kPa,处理20min,即得;
所述培养基包括以下组分及其质量百分数:葡萄糖1%,酵母粉2%,磷酸氢二钾0.01%,硫酸镁0.4%,胰蛋白胨3%,发酵助剂0.3%,纯化水92.29%;所述发酵助剂由草酸和蛋氨酸按质量比2:15组成;所述培养基的pH为7.0。
实施例2、一种红色红球菌免疫增强剂
所述免疫增强剂为红色红球菌的培养物,所述红色红球菌的培养物的制备方法为:将红色红球菌置于添加有培养基的30L的发酵罐中培养36h,培养的条件为:搅拌转速200r/min,通气量1:1.0、接种量6%、装液量为罐容积的70%、温度30℃,高温高压灭活,所述高温高压灭活的具体操作为121℃,101kPa,处理20min,即得;
所述培养基包括以下组分及其质量百分数:葡萄糖2%,酵母粉4%,磷酸氢二钾0.02%,硫酸镁0.7%,胰蛋白胨5%,发酵助剂0.5%,纯化水87.78%;所述发酵助剂由草酸和蛋氨酸按质量比4:10组成;所述培养基的pH为7.2。
实施例3、一种红色红球菌免疫增强剂
所述免疫增强剂为红色红球菌的培养物,所述红色红球菌的培养物的制备方法为:将红色红球菌置于添加有培养基的30L的发酵罐中培养30h,培养的条件为:搅拌转速200r/min,通气量1:1.0、接种量6%、装液量为罐容积的70%、温度30℃,高温高压灭活,所述高温高压灭活的具体操作为121℃,101kPa,处理20min,即得;
所述的红色红球菌免疫增强剂,所述培养基包括以下组分及其质量百分数:葡萄糖1%,酵母粉3%,磷酸氢二钾0.01%,硫酸镁0.5%,胰蛋白胨4%,发酵助剂0.4%,纯化水91.09%;所述发酵助剂由草酸和蛋氨酸按质量比3:14组成;所述培养基的pH为7.2。
实施例4、一种禽用油乳剂灭活疫苗的制备方法
所述禽用油乳剂灭活疫苗的制备方法,包括如下步骤:
I.红色红球菌免疫增强剂样本灭菌处理及定量
取实施例3制得的红色红球菌免疫增强剂液体样本若干,采用121℃高压蒸汽灭活30min,灭菌后样本待温度降至室温时,4℃保存备用。
红色红球菌免疫增强剂样本使用前,需进行定量。定量过程为:无菌移取30mL免疫增强剂样本平分到3支15mL离心管中,12000r/min高速离心5min,弃除上清液后,置于103℃干燥箱中充分干燥2小时,测定样本干物质重量。
II.添加红色红球菌免疫增强剂的禽用油乳剂灭活疫苗的制备
(1)抗原水相的制备
取2mg经过定量的红色红球菌免疫增强剂添加到新城疫+H9混合抗原液中(新城疫抗原:H9亚型禽流感抗原=1:1,新城疫抗原和H9亚型禽流感抗原均为鸡胚制备抗原原液),加入5mL的Tween-80后混匀,充分混合溶解后,最终总体积为100mL,制备成抗原水相。同时设立未添加红色红球菌免疫增强剂的新城疫+H9混合抗原对照组,对照组与试验组的差异仅为是否添加红色红球菌免疫增强剂,其他均相同处理。
注意,制备抗原水相时应先制备不加红色红球菌免疫增强剂的对照组抗原水相,然后再制备含红色红球菌免疫增强剂的试验组抗原水相。
(2)乳化制备疫苗
取制备的抗原水相100mL,缓慢加入到200mL按照乳化配方制备的油相中,所述油相的制备方法为:在矿物油中加入司本-80,混匀后加入硬脂酸铝,混匀,灭菌,即得;所述矿物油(V/mL):司本-80(V/mL):硬脂酸铝(W/g)为94:6:1.5;使用IKA T25乳化机乳化,要求乳化机在抗原水相加入过程中保持5000r/min低速搅拌,待抗原水相完全加入到油相后,调节乳化机转速为12000r/min高速剪切乳化5min。乳化后制备的疫苗分装后,置于4℃保持备用,得初始的禽用油乳剂灭活疫苗。
注意,制备疫苗时应先制备不加红色红球菌免疫增强剂的对照组疫苗,然后再制备含红色红球菌免疫增强剂的试验组疫苗。
(3)禽用油乳剂灭活疫苗的检测;
将所得初始的禽用油乳剂灭活疫苗经物理性状检测,安全性检测、效力试验检测及商品动物免疫检测,验证合格后,即得。
对比例1、一种红色红球菌免疫增强剂
所述免疫增强剂为红色红球菌的培养物,所述红色红球菌的培养物的制备方法为:将红色红球菌置于添加有培养基的30L的发酵罐中培养30h,培养的条件为:搅拌转速200r/min,通气量1:1.0、接种量6%、装液量为罐容积的70%、温度30℃,高温高压灭活,所述高温高压灭活的具体操作为121℃,101kPa,处理20min,即得;
所述培养基包括以下组分及其质量百分数:葡萄糖1%,酵母粉3%,磷酸氢二钾0.01%,硫酸镁0.5%,胰蛋白胨4%,发酵助剂0.4%,纯化水91.09%;所述发酵助剂由草酸和蛋氨酸按质量比1:1组成;所述培养基的pH为7.2。
对比例2、一种红色红球菌免疫增强剂
所述免疫增强剂为红色红球菌的培养物,所述红色红球菌的培养物的制备方法为:将红色红球菌置于添加有培养基的30L的发酵罐中培养30h,培养的条件为:搅拌转速200r/min,通气量1:1.0、接种量6%、装液量为罐容积的70%、温度30℃,高温高压灭活,所述高温高压灭活的具体操作为121℃,101kPa,处理20min,即得;
所述培养基包括以下组分及其质量百分数:葡萄糖1%,酵母粉3%,磷酸氢二钾0.01%,硫酸镁0.5%,胰蛋白胨4%,发酵助剂0.4%,纯化水91.09%;所述发酵助剂为蛋氨酸。
对比例3、一种禽用油乳剂灭活疫苗的制备方法
所述禽用油乳剂灭活疫苗的制备方法与实施例4类似;
与实施例4的不同在于,红色红球菌免疫增强剂为对比例1制备的红色红球菌免疫增强剂。
对比例4、一种禽用油乳剂灭活疫苗的制备方法
所述禽用油乳剂灭活疫苗的制备方法与实施例4类似;
与实施例4的不同在于,红色红球菌免疫增强剂为对比例2制备的红色红球菌免疫增强剂。
试验例一、类脂化合物和多糖含量的测定
取实施例3、对比例1、对比例2所得红色红球菌的培养物,加入等量的5%KOH溶液,95℃水浴处理35min,破碎细菌细胞壁,进行冷冻干燥得到细胞壁骨架粉末。
(1)类脂化合物含量的测定
称取细胞壁骨架粉末50mg,加入2.5%NaOH溶液2mL,在甲醇∶苯(1∶1,v/v)20mL中回流水解2h,以1mol/L HCl中和,***提取三次,提取液浓缩,经无水乙醇精制,测定其类脂化合物含量。
(2)多糖含量的测定
称取细胞壁骨架粉末50mg于试管中,加1mol/L H2SO4 5mL,封管后于100℃水浴中水解8h,水解物的液层经提取得多糖,测定其多糖含量。
类脂化合物和多糖含量的测定结果如表1所示。
表1:类脂化合物和多糖含量的测定结果
测定项目 | 实施例3 | 对比例1 | 对比例2 |
类脂化合物(%) | 20.3 | 16.4 | 12.7 |
多糖(%) | 51.6 | 43.5 | 37.2 |
由表1可知,采用本发明的方法所得红色红球菌的培养物中类脂化合物、多糖含量明显高于对比例1、对比例2。
试验例二、禽用油乳剂灭活疫苗物理性状检测
取实施例4制备并分装的疫苗,回温到室温后,分别检测以下物理性状:
A.每组疫苗取10mL样本用旋转粘度计检测疫苗粘度。
B.将疫苗缓慢滴加到静置水面上,观察疫苗扩散情况。
C.每组取30mL疫苗,分别分装入3支10mL锥底离心管,3000r/min离心15min,观察有无分层破乳现象。如有破乳分层,说明疫苗制备不成功,需重新制备。
D.上述经过离心的疫苗,标记后分别置于37℃,室温,4℃保存1个月,观察是否破乳。
试验结果如下:
A.试验组疫苗粘度33.4cp,对照组疫苗43.3cp,二者均合格。
B.试验组疫苗与对照组疫苗均合格。
C.试验组疫苗与对照组疫苗均无破乳,二者均合格。
D.试验组疫苗与对照组疫苗均无破乳,二者均合格。
试验例三、禽用油乳剂灭活疫苗安全性试验
采用实施例4试验组制备的疫苗免疫21日龄SPF鸡,2mL/只,每组疫苗免疫10只,每日观察鸡只健康状态,连续观察14天。
试验结果显示,SPF鸡无死亡,健康状况良好,由此说明采用本发明免疫增强剂制得的疫苗合格,安全。
试验例四、禽用油乳剂灭活疫苗效力性试验
分别采用实施例4试验组、对照组制备的疫苗免疫21日龄SPF鸡,0.3mL/只,每组疫苗免疫10只,每只鸡标记脚号,疫苗注射后1周起,每周采血分离血清进行ND和H9亚型禽流感的HI检测,连续检测3周,另外设置空白组。试验结果如表1、表2所示。
表2:新流二联疫苗的效力对比试验H9抗体测定结果
表3:新流二联疫苗效力对比试验ND抗体水平比较
由表2、表3可知,免疫后21天,采用本发明免疫增强剂制得的疫苗的试验组的H9抗体、ND抗体水平显著高于对照组,且一直持续到实验结束,由此可得,本发明免疫增强剂可以起到明显增强机体免疫力的作用。
试验例五、商品鸡免疫试验
采用市购的商品鸡,于8日龄左右分别采用实施例4试验组、对比例3、对比例4、对照组制备的疫苗进行疫苗免疫,0.3mL/只,每组疫苗免疫20只,每只鸡标记脚号,疫苗注射后1周起,每周采血分离血清进行ND和H9亚型禽流感的HI检测,连续检测8周,试验结果如表4所示。
表4:商品鸡免疫试验结果
由表4可知,采用本发明免疫增强剂制得的疫苗的免疫效果明显优于对照组的免疫效果。
综上可知,采用本发明免疫增强剂制得的疫苗安全、高效。
Claims (6)
1.一种红色红球菌免疫增强剂,其特征在于,所述免疫增强剂为红色红球菌的培养物,所述红色红球菌的培养物的制备方法为:将红色红球菌置于添加有培养基的30L的发酵罐中培养24-36h,高温高压灭活,即得;所述培养基由以下质量百分比的组分制成:葡萄糖1-2%,酵母粉2-4%,磷酸氢二钾0.01-0.02%,硫酸镁0.4-0.7%,胰蛋白胨3-5%,发酵助剂0.3-0.5%,纯化水87.78-92.29%;
所述红色红球菌购自广东省微生物菌种保藏中心,GDMCC No.:1.819;所述发酵助剂为草酸和蛋氨酸;所述草酸和蛋氨酸的质量比为2-4:10-15。
2.如权利要求1所述的红色红球菌免疫增强剂,其特征在于,所述培养基由以下质量百分比的组分制成:葡萄糖1%,酵母粉3%,磷酸氢二钾0.01%,硫酸镁0.5%,胰蛋白胨4%,发酵助剂0.4%,纯化水91.09%。
3.如权利要求1所述的红色红球菌免疫增强剂,其特征在于,所述草酸和蛋氨酸的质量比为3:14。
4.如权利要求1-3任一项所述的红色红球菌免疫增强剂在制备禽用油乳剂灭活疫苗中的应用;所述禽用油乳剂灭活疫苗为新城疫禽流感双联疫苗;所述抗原为新城疫抗原:H9亚型禽流感抗原=1:1。
5.一种禽用油乳剂灭活疫苗,由权利要求1-3任一项所述的红色红球菌免疫增强剂组成;所述禽用油乳剂灭活疫苗为新城疫禽流感双联疫苗;所述抗原为新城疫抗原:H9亚型禽流感抗原=1:1。
6.如权利要求5所述的禽用油乳剂灭活疫苗的制备方法,其特征在于,包括如下步骤:
S1取红色红球菌免疫增强剂,采用121℃高压蒸汽灭活30min,灭菌后待温度降至室温时,4℃保存备用;
S2将红色红球菌免疫增强剂进行定量,得定量的红色红球菌免疫增强剂;
S3将步骤S2所得定量的红色红球菌免疫增强剂按乳化配方添加至混合抗原水相中,搅拌均匀并进行常规乳化,得初始的禽用油乳剂灭活疫苗;
S4将步骤S3所得初始的禽用油乳剂灭活疫苗经物理性状检测,安全性检测、效力试验检测及商品动物免疫检测,验证合格后,即得。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111196852.9A CN114028554B (zh) | 2021-10-14 | 2021-10-14 | 一种红色红球菌免疫增强剂及其在禽用疫苗中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111196852.9A CN114028554B (zh) | 2021-10-14 | 2021-10-14 | 一种红色红球菌免疫增强剂及其在禽用疫苗中的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114028554A CN114028554A (zh) | 2022-02-11 |
CN114028554B true CN114028554B (zh) | 2023-12-12 |
Family
ID=80134888
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111196852.9A Active CN114028554B (zh) | 2021-10-14 | 2021-10-14 | 一种红色红球菌免疫增强剂及其在禽用疫苗中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114028554B (zh) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1735431A (zh) * | 2002-09-06 | 2006-02-15 | 伦敦大学 | 作为免疫调节物的全细菌细胞 |
CN107684621A (zh) * | 2017-07-25 | 2018-02-13 | 华南农业大学 | 类白喉棒状杆菌作为免疫佐剂在禽用油乳剂灭活疫苗中的应用 |
CN109576180A (zh) * | 2018-12-17 | 2019-04-05 | 北京利昂盛生物技术有限公司 | 一株赤红球菌及其作为免疫佐剂在制备疫苗中的应用 |
CN110935017A (zh) * | 2019-12-26 | 2020-03-31 | 广州科力生物科技有限公司 | 一种诺卡氏菌免疫增强剂在禽用疫苗制备中的应用 |
-
2021
- 2021-10-14 CN CN202111196852.9A patent/CN114028554B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1735431A (zh) * | 2002-09-06 | 2006-02-15 | 伦敦大学 | 作为免疫调节物的全细菌细胞 |
CN107684621A (zh) * | 2017-07-25 | 2018-02-13 | 华南农业大学 | 类白喉棒状杆菌作为免疫佐剂在禽用油乳剂灭活疫苗中的应用 |
CN109576180A (zh) * | 2018-12-17 | 2019-04-05 | 北京利昂盛生物技术有限公司 | 一株赤红球菌及其作为免疫佐剂在制备疫苗中的应用 |
CN110935017A (zh) * | 2019-12-26 | 2020-03-31 | 广州科力生物科技有限公司 | 一种诺卡氏菌免疫增强剂在禽用疫苗制备中的应用 |
Also Published As
Publication number | Publication date |
---|---|
CN114028554A (zh) | 2022-02-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN109666609B (zh) | 一种赤红球菌发酵方法及其作为佐剂在动物疫苗中的应用 | |
CN103263666B (zh) | 猪圆环病毒2型、猪支原体肺炎二联灭活疫苗及其制备方法 | |
CN102086447A (zh) | 鸭病毒性肝炎毒株及灭活疫苗 | |
CN104946600B (zh) | 一种h9亚型禽流感病毒株 | |
CN110935017A (zh) | 一种诺卡氏菌免疫增强剂在禽用疫苗制备中的应用 | |
CN113957012B (zh) | 一种鸡滑液囊支原体培养基及其制备方法 | |
CN114028554B (zh) | 一种红色红球菌免疫增强剂及其在禽用疫苗中的应用 | |
CN102793920B (zh) | 复方免疫增强剂、禽用灭活疫苗及其制备方法 | |
CN109055320B (zh) | 一株传染性支气管炎病毒分离株及在疫苗制备中的应用 | |
CN113975384B (zh) | 一种红色红球菌免疫增强剂及其在鱼用疫苗中的应用 | |
CN113648407A (zh) | 一种诺卡氏菌免疫增强剂在鱼用疫苗中的应用 | |
CN105879025A (zh) | 一种免疫佐剂组合物及其制备方法 | |
CN112618706B (zh) | 沙门氏菌、鸭疫里默氏杆菌、大肠埃希氏杆菌病三联疫苗 | |
CN113957007B (zh) | 一种鸡滑液囊支原体灭活疫苗 | |
CN110448690B (zh) | 一种鸡传染性鼻炎(a型+b型+c型)、鼻气管鸟疫杆菌病(a型)二联灭活疫苗 | |
CN112062836B (zh) | 猪塞尼卡谷病毒高效价阳性血清及其制备方法 | |
CN106075424B (zh) | 一种禽流感病毒疫苗 | |
CN111000995A (zh) | 猪用三联灭活疫苗及其制备方法和应用 | |
CN110974949A (zh) | 猪用二联灭活疫苗及其制备方法和应用 | |
CN114015658B (zh) | 一种h9n2亚型禽流感和鸡滑液囊支原体的二联灭活疫苗 | |
CN117224667B (zh) | 一种禽流感、新城疫病毒疫苗组合物及其应用 | |
CN117100849B (zh) | 一种赤羽病毒阳性血清及其制备方法 | |
CN106085966B (zh) | 一种禽流感病毒株 | |
CN109486741B (zh) | 一种副鸡禽杆菌的灭活方法 | |
CN106520636B (zh) | 一种猪支气管波氏杆菌菌株 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |