WO2014208822A1 - Nouveau adénovirus aviaire et vaccin correspondant - Google Patents

Nouveau adénovirus aviaire et vaccin correspondant Download PDF

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Publication number
WO2014208822A1
WO2014208822A1 PCT/KR2013/008898 KR2013008898W WO2014208822A1 WO 2014208822 A1 WO2014208822 A1 WO 2014208822A1 KR 2013008898 W KR2013008898 W KR 2013008898W WO 2014208822 A1 WO2014208822 A1 WO 2014208822A1
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WIPO (PCT)
Prior art keywords
poultry
vaccine
adenovirus
poultry adenovirus
fadv
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PCT/KR2013/008898
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English (en)
Korean (ko)
Inventor
송창선
이중복
최인수
박승용
Original Assignee
건국대학교기술지주주식회사
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Priority claimed from KR1020130087427A external-priority patent/KR101564316B1/ko
Application filed by 건국대학교기술지주주식회사 filed Critical 건국대학교기술지주주식회사
Priority to CN201380079205.7A priority Critical patent/CN105593364A/zh
Publication of WO2014208822A1 publication Critical patent/WO2014208822A1/fr

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    • 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
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5252—Virus inactivated (killed)
    • 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

Definitions

  • the present invention relates to novel poultry adenovirus and vaccines thereof.
  • FAdV Fowl adenovirus
  • group 1 poultry adenovirus FAdV belongs to the family Adenoviridae, and gemone consists of double-stranded DNA that is not segmented.
  • the major serotypes that cause damage to the domestic poultry industry are known to be caused by type 4, type 8 or type 11.
  • Inclusion hepatitis is found in most serotypes, and type 4 is accompanied by pericarditis. It is known to be the strongest.
  • Adenovirus infections are diseases in which liver cells are infected as a main target, forming characteristic inclusion bodies and causing death. Inclusion hepatitis can be transmitted either vertically or horizontally. Vertical propagation usually occurs between three to four weeks of age, and vertical propagation has occurred before seven days of age. The mortality rate of single infection is low around 10%, but mortality is higher when combined with immunosuppressive diseases such as Gamboro and chicken infectious anemia. Infection of serotype 4 with pericardial hydrocephalus is associated with relatively high morbidity and mortality, and mortality rates of up to 80% are known in susceptible broilers, causing significant economic losses to the domestic poultry industry. Situation.
  • Pericarditis is characterized by high morbidity and mortality due to infection alone, even in the absence of immunosuppressive diseases, unlike conventional inclusion hepatitis.
  • Pericarditis is a disease that is highly susceptible to young age, and because it is possible to spread eggplants, it is asymptomatically infected in breeders, and it is a disease that can cause serious disease due to eggplants of later chicks.
  • serotype 4 was the highest in 46% of cases of inclusion hepatitis reported from 2007 to 2010, and other types 11 (31%) and 8b (23%). ), Type 4, type 8b and type 11 accounted for a high percentage. In addition, 72% of the total outbreaks were reported in broilers, and laying hens and native chickens were the rest. The damage caused by inclusion hepatitis was found to be greatest in broilers. (Figure 1)
  • the present invention has been made by the above necessity, and an object of the present invention is to provide a novel poultry adenovirus isolated from Korea.
  • the present invention provides a FAdV K4 poultry adenovirus deposited with accession number KCTC 12425BP.
  • the strain of the present invention was deposited on June 12, 2013 to the Korea Institute of Bioscience and Biotechnology Center (125, Yuseong-gu, Daejeon, Daejeon, Korea, Korea Biotechnology Research Institute, 305-806).
  • the virus is preferably isolated from domestic chickens, preferably comprising the nucleotide sequence of SEQ ID NO: 1, but is not limited thereto.
  • the present invention also provides a poultry protection vaccine against diseases caused from poultry adenovirus infection comprising the poultry adenovirus of the present invention and a pharmaceutically acceptable carrier or diluent.
  • the vaccine is preferably effective in preventing or treating inclusion hepatitis, it is preferably in an inactivated form, preferably further comprises an adjuvant, and is infectious to poultry. It is preferred to include one or more vaccine components of other pathogens, but is not limited thereto.
  • the present invention comprises inoculating a poultry adenovirus defined in the present invention on a substrate susceptible to infection; b) propagating the poultry adenovirus; And c) provides a method for producing poultry adenovirus comprising the step of collecting the poultry adenovirus-containing material.
  • the substrate is one selected from the group consisting of embryonic liver cells (CEL), chicken embryo fibroblasts (CEF), chicken kidney cells (CK), and Vero cell lines.
  • CEL embryonic liver cells
  • CEF chicken embryo fibroblasts
  • CK chicken kidney cells
  • Vero cell lines Preferably, the cells are but are not limited thereto.
  • the present invention comprises the step of combining the collected poultry adenovirus obtained by the method of the present invention with a pharmaceutically acceptable carrier or diluent, and if necessary, the step is carried out after inactivation of the poultry adenovirus It provides a method for producing a poultry protection vaccine against diseases caused from poultry adenovirus infection.
  • the present invention also provides a method for controlling a disease caused from poultry adenovirus infection in poultry comprising administering the vaccine of the present invention to birds.
  • Vaccines of the invention can be prepared according to conventional methods commonly used, for example, in commercial live inactivated poultry adenovirus vaccines. Preparation of veterinary vaccine compositions is particularly described in "Handbunch der Schutzimpfungen in der Tier Kunststofftechnik” (ed. Mays, A. et al., Verlag Paul Parey, Berlin und Hamburg, Germany, 1984) and "Vaccines or Veterinary Applications” (ed. Peters, AR). Et al., Butterworth-Heinemann Ltd, 1993.
  • the purpose of inactivating the harvested virus after the propagation step is to prevent regeneration of the virus. In general, this can be done by chemical or physical means. Chemical inactivation can be carried out, for example, by treating the virus with enzymes, formaldehyde, beta-propiolactone, ethylene-imine or derivatives thereof. If necessary, the deactivated compound is later neutralized.
  • the formaldehyde inactivated material may be neutralized with, for example, thiosulfate.
  • Physical inactivation may be preferably carried out by irradiating the virus with sufficient energy, for example UV light. If necessary, the pH may be adjusted to a value of about 7 after treatment.
  • Vaccines containing inactivated poultry adenovirus may, for example, comprise one or more of the aforementioned pharmaceutically acceptable carriers or diluents suitable for this purpose.
  • the inactivated vaccine of the present invention comprises one or more compounds with adjuvant activity.
  • Suitable compounds or compositions for this purpose include vegetable oils such as aluminum hydroxide, -phosphate, -oxide, mineral oil, vitamin E acetate, and oil-in-water or water-in-oil emulsions based on saponins.
  • Inactivated vaccines are usually administered parenterally, ie intramuscularly or subcutaneously.
  • the vaccine of the present invention comprises as an active ingredient an effective amount of poultry adenovirus, i.e., an amount to immunize poultry adenovirus material which will induce immunity in vaccinated birds or their offspring against attack by toxic viruses (antigen administration). .
  • Immunity is defined herein to induce a significantly higher level of protection in avian populations after vaccination compared to the non-vaccinated group.
  • the inactivated vaccine comprises an antigen equivalent to 10 4 -10 10 TCID50 per bird.
  • the poultry adenovirus vaccine of the present invention can be used effectively in chickens, but other poultry such as turkey, guinea fowl and quail can also be vaccinated effectively.
  • Chickens include edible chickens, cloned cattle, and laying eggs.
  • the present invention can effectively protect poultry from poultry adenovirus infection by providing new poultry adenoviruses, vaccines comprising the same and methods for their preparation.
  • Figure 1 shows the serotype and incidence rate of inclusion hepatitis virus reported in Korea between 2007 and 2010 ⁇ Source: Agriculture, Forestry and Livestock Quarantine Headquarters>
  • livers were collected from broilers from Gyeonggi-based broiler farms, and sterile phosphate buffer solution (pH7.2) was added to make 10 wt% emulsion.
  • Cells and tissues were precipitated by centrifugation at 3,000 g for 15 minutes, and the supernatant was filtered with a 0.45 ⁇ m syringe filter.
  • FAdV K4 strains were finally identified by polymerase chain reaction (PCR) by 11-day-old SPF embryonated chorioallantoic membrane (CAM) inoculation.
  • IBV Infectious bronchitis virus
  • NDV Newcastle disease
  • IBDV Infectious bursal virus
  • CIAV chicken infectious anemia virus
  • RT-PCR reverse transcription polymerase chain reaction
  • PCR polymerase chain reaction
  • DNA was extracted by inoculating the 11-day-old SPF embryonated eggs with 150 ⁇ l of the urinary membrane solution harvested 5 days later.
  • the DNA thus obtained was mixed with 5 ⁇ l of DNA solution, 5 ⁇ l of 10 ⁇ PCR buffer, 4 ⁇ l of 2.5 mM dNTPs, 1 ⁇ l of each primer, 0.5 ⁇ l of Taq polymerase and 33.5 ⁇ l of DW.
  • Table 1 shows the nucleotide sequence and position of primer set used for HEXON base analysis.
  • Table 2 shows the HEXON sequences of FAdV K4 virus
  • the formalin solution was added to the virus culture at 0.1 ° C. After inactivation for 24 hours, the oil antigen adjuvant ISA70 and antigen, which are widely used in animal poisoning vaccine, were emulsified at a ratio of 30:70.
  • the final virus titer after emulsification was 5 ⁇ 10 5 tissue culture infective dose (TCID 50 ) / 1 dose (0.5 mL).
  • Table 3 shows the clinical symptoms and death of three weeks-old SPF inoculation system after FAdV K4 inactivated oil vaccine.
  • Table 4 shows the changes in body weight and granuloma formation in the three-week-old SPF inoculation system after FAdV K4 inactivated oil vaccine.
  • Table 5 shows the antibody-forming ability of the 6-week-old SPF inoculation system after FAdV K4 inactivated oil vaccine inoculation.
  • Table 6 shows the clinical symptoms and mortality of allogeneic and heterologous serotype virus challenge after FAdV K4 inactivated oil vaccine.
  • Table 7 shows gross lesions and virus re-separation rates for allogeneic and heterologous serotype virus challenge after FAdV K4 inactivated oil vaccine.
  • the 1-day-old posterior chicks of the vaccinated group and the non-vaccinated control group were divided into 10 groups using 100 numbers in the test group and 50 numbers in the control group, and homologous and heterologous serotypes (serum types 3, 4, 8, 9, 11).
  • Type 2 After challenge inoculation of 10 6 TCID 50 through the muscle, the clinical symptoms and mortality were observed for 2 weeks, and then 2 weeks after the inoculation, all groups of chickens were autopsied to examine the gross lesions caused by adenovirus infection. And histological lesions of necrosis, pericardia in type 4) and liver.
  • Table 8 shows antibody-forming ability in 17-week-old broiler breeders after FAdV K4 inactivated oil vaccine
  • Table 9 shows the clinical symptoms and mortality rates of allogeneic and heterologous serotype virus challenge in later chicks inoculated with FAdV K4 inactivated oil vaccine.
  • Table 10 shows gross and tissue lesions in descendants of FAdV K4 inactivated oil vaccine at 2 weeks after allogeneic and heterologous serotype virus challenge.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Virology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Immunology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente invention concerne un nouveau adénovirus aviaire et un vaccin correspondant.
PCT/KR2013/008898 2013-06-27 2013-10-04 Nouveau adénovirus aviaire et vaccin correspondant WO2014208822A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201380079205.7A CN105593364A (zh) 2013-06-27 2013-10-04 新型家禽腺病毒及其疫苗

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KR20130074933 2013-06-27
KR10-2013-0074933 2013-06-27
KR10-2013-0087427 2013-07-24
KR1020130087427A KR101564316B1 (ko) 2013-06-27 2013-07-24 신규한 가금 아데노 바이러스 및 그 백신

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112094824A (zh) * 2020-08-19 2020-12-18 湖北省农业科学院畜牧兽医研究所 表达禽腺病毒4型截短Fiber2蛋白的重组新城疫病毒耐热疫苗株及其制备方法与应用
CN112538464A (zh) * 2020-12-07 2021-03-23 中国农业科学院哈尔滨兽医研究所（中国动物卫生与流行病学中心哈尔滨分中心） 血清4型禽腺病毒反向遗传疫苗株rHN20及其构建方法和应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6296852B1 (en) * 1993-04-14 2001-10-02 Commonwealth Scientific And Industrial Research Organisation Recombinant avian adenovirus vector
WO2003039593A1 (fr) * 2001-11-08 2003-05-15 Akzo Nobel N.V. Vaccin contre l'adenovirus aviaire
US20110165224A1 (en) * 2009-12-15 2011-07-07 University Of Saskatchewan Vaccines for inclusion body hepatitis

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6296852B1 (en) * 1993-04-14 2001-10-02 Commonwealth Scientific And Industrial Research Organisation Recombinant avian adenovirus vector
WO2003039593A1 (fr) * 2001-11-08 2003-05-15 Akzo Nobel N.V. Vaccin contre l'adenovirus aviaire
US20110165224A1 (en) * 2009-12-15 2011-07-07 University Of Saskatchewan Vaccines for inclusion body hepatitis

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KIM, JI YE ET AL.: "Safety and Efficacy of Fowl Adenovirus Serotype-4 Inactivated Oil Emulsion Vaccine", KOREAN JOURNAL OF POULTRY SCIENCE, vol. 37, no. 3, 2010, pages 255 - 263 *
PARK, HONG- SU ET AL.: "Isolation and characterization of fowl adenovirus serotype 4 from chickens with hydropericardium syndrome in Korea", KOREAN JOURNAL OF VETERINARY RESEARCH, vol. 51, no. 3, 2011, pages 209 - 216 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112094824A (zh) * 2020-08-19 2020-12-18 湖北省农业科学院畜牧兽医研究所 表达禽腺病毒4型截短Fiber2蛋白的重组新城疫病毒耐热疫苗株及其制备方法与应用
CN112538464A (zh) * 2020-12-07 2021-03-23 中国农业科学院哈尔滨兽医研究所（中国动物卫生与流行病学中心哈尔滨分中心） 血清4型禽腺病毒反向遗传疫苗株rHN20及其构建方法和应用

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