WO2005112995A1 - Vaccin associe inactive pour la maladie respiratoire du porc et procede de production associe - Google Patents

Vaccin associe inactive pour la maladie respiratoire du porc et procede de production associe Download PDF

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Publication number
WO2005112995A1
WO2005112995A1 PCT/KR2005/001207 KR2005001207W WO2005112995A1 WO 2005112995 A1 WO2005112995 A1 WO 2005112995A1 KR 2005001207 W KR2005001207 W KR 2005001207W WO 2005112995 A1 WO2005112995 A1 WO 2005112995A1
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WO
WIPO (PCT)
Prior art keywords
vaccine
virus
cell
inactivated
disease
Prior art date
Application number
PCT/KR2005/001207
Other languages
English (en)
Inventor
In-Joong Yoon
Sung-Min Lee
Sung-Sik Yoo
Original Assignee
Choongang Vaccine Laboratory Co., Ltd.
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.)
Filing date
Publication date
Application filed by Choongang Vaccine Laboratory Co., Ltd. filed Critical Choongang Vaccine Laboratory Co., Ltd.
Publication of WO2005112995A1 publication Critical patent/WO2005112995A1/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
    • 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
    • A61K2039/52Bacterial cells; Fungal cells; Protozoal cells
    • A61K2039/521Bacterial cells; Fungal cells; Protozoal cells inactivated (killed)
    • 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
    • A61K2039/5252Virus inactivated (killed)
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55505Inorganic adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55566Emulsions, e.g. Freund's adjuvant, MF59
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/70Multivalent vaccine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/02Bacterial antigens
    • A61K39/0241Mollicutes, e.g. Mycoplasma, Erysipelothrix
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/02Bacterial antigens
    • A61K39/102Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
    • 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
    • C12N2770/10011Arteriviridae
    • C12N2770/10034Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • the present invention relates to a vaccine for porcine respiratory diseases. Specifically, the present invention relates to an inactivated mixed (combined) vaccine for porcine respiratory diseases.
  • porcine respiratory diseases have been serious problem which results in severe economic loss to farms.
  • PMS post-weaning multisystemic wasting syndrome
  • PRDC porcine respiratory disease complex
  • various vaccines have been introduced.
  • a vaccine for any one of conditions was not effective in many cases.
  • a few of mixed vaccines were developed and applied at several farms. The mixed vaccines, however, were not
  • PRRS Reproductive & Respiratory Syndrome
  • the Glasser's disease in a pig is highly infective to a 2 ⁇ 4 month
  • This disease develops by the infection of a pathogenic microbial, which
  • a pig can be activated by Mycoplasma hyopneumoniae or PRRS virus.
  • This disease mainly
  • the PRRS virus is a RNA virus which has envelope and
  • pneumonia makes the affected pig to be very sensitive to secondary infections of other respiratory diseases, for example, Glasser's disease,
  • This invention is for providing a mixed (combined) vaccine for
  • invention is for providing an inactivated mixed vaccine for preventing
  • PRRS reproductive and respiratory syndrome
  • Another object of this invention is to provide an inactivated mixed
  • porcine respiratory diseases, PMWS and PRDC of a growing-finishing pig porcine respiratory diseases, PMWS and PRDC of a growing-finishing pig.
  • object of this invention is to provide a novel method of
  • the vaccine for Glasser's disease is the vaccine for Glasser's disease
  • the vaccine for PRRS was prepared using MN-HS (Minnesota)
  • PRRSV Korean isolate CNV-1, Korean J. Vet Res (1999) 39(2):
  • CPE cytopathic effect
  • the mixed vaccine composition of this invention preferably a
  • the composition comprises in a range of 20 - 30% (vol/vol) vaccine components.
  • Haemophilus parasuis S4 strain (0.D 0.4 - 0.5 at 410 nm)
  • Haemophilus parasuis S5 strain (0.D 0.4 ⁇ 0.5 at 410 nm)
  • Mycoplasma hyopneumoniae J/101 (0.D 0.
  • antibody titer to PRRS virus provides more accurate antibody titer.
  • finished stage of marketed pigs daily weight
  • the average weight of the pigs given with the mixed vaccine of this invention was in a range of 3.1-4.2
  • the mixed vaccine of this invention was higher than that of the pigs
  • Fig. 1 to Fig. 3 show examples of pneumonia scores.
  • Fig. 1 is an example of pneumonia, and shows percentage of each lobe for entire normal lung.
  • Fig. 2 is an example of pneumonia, and shows lung lesion having 12% of lobe score.
  • Fig. 3 is an example of pneumonia, and shows lung lesion having 20% of lobe score.
  • Example 1 Isolation and culturing virus
  • TSB Tryptic Soy Broth
  • NAD ⁇ -Nicotinamide adenine dinucleotide 45 ⁇ g/mi , yeast extract 0.5%
  • J/101 strain obtained from National Veterinary Research and Quarantine Service, which causes swine enzootic pneumonia, was delivered in
  • mycoplasma medium (table 1) and was incubated. After the isolation, the incubated strain was in freeze-drying and cryopreservation at -80 ° C.
  • mycoplasma medium (table 1) in 1/3 volume of the medium, and incubated
  • the swine lung macrophage cell the STL cell, or the
  • A-72 cell was suspended in a cell culture medium (table 2).
  • the cell culture medium (table 2).
  • example 1 were delivered in a TSB medium including ⁇ -NAD ( ⁇ -
  • Nicotinamide adenine dinucleotide 45 ⁇ g/ml , yeast extract 0.5% and were
  • PRRS virus MN-HS or CNV-1 was inoculated
  • UV spectrophotometer UV spectrophotometer.
  • the inactivated PRRS virus was 1/10 diluted, and
  • STL wine testis cell line
  • the virus content was determined with the appearance of CPE following the PRRS virus inoculation.
  • virus content was over 10 6,0 TCIDso/m ⁇ .
  • Example 3 Preparation of inactivated mixed vaccine Strain isolation, disease causing agent isolation and inactivation
  • vaccine components were 30% (vol/vol) of the whole mixed vaccine
  • Haemophilus parasuis S4 (at 410 nm, O.D 0.45), Haemophilus parasuis S5 (at 410 nm, O.D 0.45), Mycoplasma hyopneumoniae J/101 (at 410 nm, O.D 0.1) and PRRS MN-HS (10 6 '°TCID 50 /ml) .
  • the vaccine composition it was filtered with copper net. Then, the
  • the composition did not have any taste and smell.
  • the vaccine sample in each lot was transferred to Thioglycollate medium (Thio), Nutrient agar
  • NA Nutrient broth
  • NB Nutrient broth
  • Thioglycollate medium Thioglycollate medium (Thio), Nutrient agar (NA) and Nutrient broth (NB),
  • mice weighing 13 g and 10 mice weighing 15 g were used.
  • Respective vaccine samples (0.5 ml, lot no. 1-3) of example 3 were delivered intraperitoneally to 5 mice weighing 13 g and 5 mice weighing 15 g.
  • respective vaccine samples (0.5 ml, lot no. 1-3) of example 3 were delivered subcutaneously to 5 mice weighing 13 g and to 5 mice weighing 15 g.
  • the vaccinated mice were monitored in comparison to 5 untreated control mice. All the mice, which were injected with the mixed vaccine of this invention, survived during the monitoring period (table 6).
  • Respective 12 guinea pigs weighing 300 g and 350 g were used in this experiment. Respective 4 guinea pigs weighing 300 g and 4 guinea pigs weighing 350 g were injected intramuscularly by the respective vaccine sample of example 3 (0.1 ml). And respective 4 guinea pigs weighing 300 g and 4 guinea pigs weighing 350 g were injected intradermally by the respective vaccine sample of example 3 (0.1 ml). And
  • mice 3 (0.1 ml). The vaccinated mice were monitored in comparison to 4
  • the mixed vaccine (2.0 ml, Lot no. 1) of the example 3.
  • five piglets were injected through neck muscle using the mixed vaccine (2.0 ml,
  • piglets showed clinical symptom, for example, anorexia, respiratory
  • Mycoplasma hyopneumoniae increased 80-320 fold after 2 weeks from the
  • virus was not more than 2 fold after 2 weeks from the first injection, and was in a range of 4-8 fold after 4 weeks from the second injection, respectively. Not more than 10 fold neutralizing antibody titer was detected for the untreated control pigs (table 9).
  • Example 6 Detection of neutralizing antibody titer in a guinea pig
  • guinea pigs (300-350 g) were used in this experiment. 10 of them were inoculated intramuscularly using 1 ml of the mixed vaccine of this invention, and were additionally injected with the same amount of the mixed vaccine after three weeks from the first injection. 2 of the guinea pigs were used as controls. 2 weeks after the second injection,
  • the blood samples of pigs were collected before the first injection, after three weeks from the first injection, after 2
  • ⁇ -MEM cell culture medium
  • guinea pig can be used as an excellent specimen for
  • the mixed vaccine of this invention was monitored while being stored in a refrigerator for a long time.
  • the vaccine sample was stored in a range of 2 ⁇ 7 ° C in a dark cold place.
  • 1.0 ml of it was injected through neck muscle to 1-week-old healthy piglets, which were antibody negative to Haemophilus parasuis, Mycoplasma hyopneumoniae and PRRS virus, every 3 months from the date of preparation for 21 months.
  • 2.0 ml of vaccine sample was injected to the piglets.
  • sera was collected and ELISA antibody titer (H. parasuis and M. hyopneumoniae) and neutralizing antibody titers were assayed.
  • the immunogenicity was effective and the stability was satisfactory until 21 months (table 15, 16, 17 and 18).
  • ELISA antibody titer for Haemophilus parasuis increased 80-160 fold after 2 weeks from the first injection, and increased 320-1,280 fold after 4 weeks from the second injection, respectively.
  • ELISA antibody titer for Mycoplasma hyopneumoniae increased 80-320 fold after 2 weeks from the
  • vaccine of this invention weigh in an average range of 1.5-2.0 kg more
  • the piglets inoculated with the mixed vaccine of this invention weigh in
  • lung lesion score was carried out in accordance with the known method
  • the mixed vaccine of this invention can effectively prevent
  • PRDC Pulcine Respiratory Disease Complex

Abstract

L'invention concerne un vaccin associé inactivé pour la prévention de la maladie respiratoire du porc. Le vaccin associé inactivé de l'invention qui comprend une certaine dose de souche S4 et S5 de Haemophilus parasuis, Mycoplasma hyopneumoniae, et de virus PRRS inactivés, permet de prévenir de manière efficace les maladies respiratoires du porc de type maladie de Glasser, pneumonie enzootique du porc et PRRS. En outre, le vaccin associé de l'invention peut prévenir la progression de la maladie respiratoire du porc en PRDC (complexe respiratoire du porc) et PMWS (syndrome de dépérissement post-sevrage multisystémique).
PCT/KR2005/001207 2004-04-26 2005-04-26 Vaccin associe inactive pour la maladie respiratoire du porc et procede de production associe WO2005112995A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2004-0028717 2004-04-26
KR20040028717 2004-04-26

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WO2005112995A1 true WO2005112995A1 (fr) 2005-12-01

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WO (1) WO2005112995A1 (fr)

Cited By (18)

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Publication number Priority date Publication date Assignee Title
EP1941903A1 (fr) * 2007-01-03 2008-07-09 Boehringer Ingelheim Vetmedica Gmbh Prophylaxie et traitement du PRDC
CN100419073C (zh) * 2006-09-28 2008-09-17 中国兽医药品监察所 猪喘气病活疫苗及其生产方法
CN101420975B (zh) * 2006-04-10 2012-06-27 英特威国际有限公司 抗支原体和prrsv的疫苗
US8475805B2 (en) 2007-09-04 2013-07-02 Boehringer Ingelheim Vetmedica, Inc. Methods of reducing concomitant infections in pigs with a PCV2 antigen
US8496940B2 (en) 2007-02-13 2013-07-30 Boehringer Ingelheim Vetmedica, Inc. Prevention and treatment of sub-clinical PCVD
CN103941001A (zh) * 2013-03-15 2014-07-23 河南省农业科学院 猪副嗜血杆菌快速检测试纸条
CN103941002A (zh) * 2013-03-15 2014-07-23 河南省农业科学院 猪丹毒杆菌抗原快速检测试纸条
US8865183B2 (en) 2006-12-15 2014-10-21 Boehringer Ingelheim Vetmedica, Inc. Treatment of pigs with PCV2 antigent
US9011872B2 (en) 2004-12-30 2015-04-21 Boehringer Ingelheim Vetmedica, Inc. PCV2 immunogenic compositions and methods of producing such compositions
US9011868B2 (en) 2005-12-29 2015-04-21 Boehringer Ingelheim Vetmedica, Inc. Use of a PCV2 immunogenic composition for lessening clinical symptoms in pigs
US9101561B2 (en) 2005-12-29 2015-08-11 Boehringer Ingelheim Vetmedica, Inc. Multivalent PCV2 immunogenic compositions and methods of producing such compositions
US9505808B2 (en) 2013-10-02 2016-11-29 Boehringer Ingelheim Vetmedica, Inc. PCV2 ORF2 protein variant and virus like particles composed thereof
US9561270B2 (en) 2009-09-02 2017-02-07 Boehringer Ingelheim Vetmedica, Inc. Methods of reducing virucidal activity in PCV-2 compositions and PCV-2 compositions with an improved immunogenicity
US9636389B2 (en) 2006-12-11 2017-05-02 Boehringer Ingelheim Vetmedica, Inc. Effective method of treatment of porcine circovirus and Lawsonia intracellularis infections
US9669086B2 (en) 2008-01-23 2017-06-06 Boehringer Ingelheim Vetmedica, Inc. PCV2 Mycoplasma hyopneumoniae immunogenic compositions and methods of producing such compositions
CN107589256A (zh) * 2017-09-30 2018-01-16 天津瑞普生物技术股份有限公司 副猪嗜血杆菌病4型、5型二价灭活疫苗效力的检验方法
US9919041B2 (en) 2004-12-30 2018-03-20 Boehringer Ingelheim Vetmedica, Inc. PCV2 immunogenic compositions and methods of producing such compositions
CN113907044A (zh) * 2021-11-09 2022-01-11 福建省连江县刘氏兔业养殖场 一种抗病猪品系的培育方法及其应用

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CN103961695B (zh) * 2013-02-06 2016-09-07 普莱柯生物工程股份有限公司 一种预防和治疗猪呼吸道综合征的疫苗组合物及其制备方法和应用
CN104096222B (zh) * 2013-04-08 2016-09-14 普莱柯生物工程股份有限公司 一种疫苗组合物及其制备方法和应用

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US9919041B2 (en) 2004-12-30 2018-03-20 Boehringer Ingelheim Vetmedica, Inc. PCV2 immunogenic compositions and methods of producing such compositions
US9011872B2 (en) 2004-12-30 2015-04-21 Boehringer Ingelheim Vetmedica, Inc. PCV2 immunogenic compositions and methods of producing such compositions
US10576142B2 (en) 2004-12-30 2020-03-03 Boehringer Ingelheim Vetmedica, Inc. PCV2 immunogenic compositions and methods of producing such compositions
US9925256B2 (en) 2005-12-29 2018-03-27 Boehringer Ingelheim Vetmedica, Inc. Multivalent PCV2 immunogenic compositions and methods of producing such compositions
US9987349B2 (en) 2005-12-29 2018-06-05 Boehringer Ingelheim Vetmedica, Inc. Use of a PCV2 immunogenic composition for lessening clinical symptoms in pigs
US10624963B2 (en) 2005-12-29 2020-04-21 Boehringer Ingelheim Vetmedica, Inc. Multivalent PCV2 immunogenic compositions and methods of producing such compositions
US9011868B2 (en) 2005-12-29 2015-04-21 Boehringer Ingelheim Vetmedica, Inc. Use of a PCV2 immunogenic composition for lessening clinical symptoms in pigs
US10568955B2 (en) 2005-12-29 2020-02-25 Boehringer Ingelheim Vetmedica, Inc. Use of a PCV2 immunogenic composition for lessening clinical symptoms in pigs
US9610345B2 (en) 2005-12-29 2017-04-04 Boehringer Ingelheim Vetmedica, Inc. Use of a PCV2 immunogenic composition for lessening clinical symptoms in pigs
US9669087B2 (en) 2005-12-29 2017-06-06 Boehringer Ingelheim Vetmedica, Inc. Use of a PCV2 immunogenic composition for lessening clinical symptoms in pigs
US9925255B2 (en) 2005-12-29 2018-03-27 Boehringer Ingelheim Vetmedica, Inc. Multivalent PCV2 immunogenic compositions and methods of producing such compositions
US9101561B2 (en) 2005-12-29 2015-08-11 Boehringer Ingelheim Vetmedica, Inc. Multivalent PCV2 immunogenic compositions and methods of producing such compositions
CN101420975B (zh) * 2006-04-10 2012-06-27 英特威国际有限公司 抗支原体和prrsv的疫苗
CN100419073C (zh) * 2006-09-28 2008-09-17 中国兽医药品监察所 猪喘气病活疫苗及其生产方法
US9636389B2 (en) 2006-12-11 2017-05-02 Boehringer Ingelheim Vetmedica, Inc. Effective method of treatment of porcine circovirus and Lawsonia intracellularis infections
US9517260B2 (en) 2006-12-15 2016-12-13 Boehringer Ingelheim Vetmedica, Inc. Treatment of pigs with PCV2 antigen
US8865183B2 (en) 2006-12-15 2014-10-21 Boehringer Ingelheim Vetmedica, Inc. Treatment of pigs with PCV2 antigent
WO2008081015A1 (fr) * 2007-01-03 2008-07-10 Boehringer Ingelheim Vetmedica, Inc. Traitement de prdc chez les porcs
US9522182B2 (en) 2007-01-03 2016-12-20 Boehringer Ingelheim Vetmedica, Inc. Prophylaxis and treatment of PRDC
EP3017829A1 (fr) * 2007-01-03 2016-05-11 Boehringer Ingelheim Vetmedica, Inc. Traitement de prdc chez les porcs
US10010604B2 (en) 2007-01-03 2018-07-03 Boehringer Ingelheim Vetmedica, Inc. Treatment of PRDC in pigs
EP1941903A1 (fr) * 2007-01-03 2008-07-09 Boehringer Ingelheim Vetmedica Gmbh Prophylaxie et traitement du PRDC
US9555092B2 (en) 2007-02-13 2017-01-31 Boehringer Ingelheim Vetmedica, Inc. Prevention and treatment of sub-clinical PCVD
US8496940B2 (en) 2007-02-13 2013-07-30 Boehringer Ingelheim Vetmedica, Inc. Prevention and treatment of sub-clinical PCVD
US9132187B2 (en) 2007-02-13 2015-09-15 Boehringer Ingelheim Vetmedica, Inc. Prevention and treatment of sub-clinical PCVD
US9132186B2 (en) 2007-09-04 2015-09-15 Boehringer Ingelheim Vetmedica, Inc. Reduction of concomitant infections in pigs by the use of PCV2 antigen
US8475805B2 (en) 2007-09-04 2013-07-02 Boehringer Ingelheim Vetmedica, Inc. Methods of reducing concomitant infections in pigs with a PCV2 antigen
US9669086B2 (en) 2008-01-23 2017-06-06 Boehringer Ingelheim Vetmedica, Inc. PCV2 Mycoplasma hyopneumoniae immunogenic compositions and methods of producing such compositions
US9561270B2 (en) 2009-09-02 2017-02-07 Boehringer Ingelheim Vetmedica, Inc. Methods of reducing virucidal activity in PCV-2 compositions and PCV-2 compositions with an improved immunogenicity
CN103941002B (zh) * 2013-03-15 2016-03-16 河南省农业科学院 猪丹毒杆菌抗原快速检测试纸条
CN103941001B (zh) * 2013-03-15 2016-03-16 河南省农业科学院 猪副嗜血杆菌快速检测试纸条
CN103941001A (zh) * 2013-03-15 2014-07-23 河南省农业科学院 猪副嗜血杆菌快速检测试纸条
CN103941002A (zh) * 2013-03-15 2014-07-23 河南省农业科学院 猪丹毒杆菌抗原快速检测试纸条
US9505808B2 (en) 2013-10-02 2016-11-29 Boehringer Ingelheim Vetmedica, Inc. PCV2 ORF2 protein variant and virus like particles composed thereof
US11858963B2 (en) 2013-10-02 2024-01-02 Boehringer Ingelheim Animal Health USA Inc. PCV2 ORF2 protein variant and virus like particles composed thereof
CN107589256A (zh) * 2017-09-30 2018-01-16 天津瑞普生物技术股份有限公司 副猪嗜血杆菌病4型、5型二价灭活疫苗效力的检验方法
CN113907044A (zh) * 2021-11-09 2022-01-11 福建省连江县刘氏兔业养殖场 一种抗病猪品系的培育方法及其应用

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