WO2011019134A2 - Composition vaccinale comprenant des variants de micro-organismes de salmonella pour la prévention de la typhoïde aviaire - Google Patents

Composition vaccinale comprenant des variants de micro-organismes de salmonella pour la prévention de la typhoïde aviaire Download PDF

Info

Publication number
WO2011019134A2
WO2011019134A2 PCT/KR2010/003233 KR2010003233W WO2011019134A2 WO 2011019134 A2 WO2011019134 A2 WO 2011019134A2 KR 2010003233 W KR2010003233 W KR 2010003233W WO 2011019134 A2 WO2011019134 A2 WO 2011019134A2
Authority
WO
WIPO (PCT)
Prior art keywords
salmonella
vaccine composition
jol916
vaccine
group
Prior art date
Application number
PCT/KR2010/003233
Other languages
English (en)
Korean (ko)
Other versions
WO2011019134A3 (fr
Inventor
이존화
마쓰다기꾸
아툴 차우다리에이.
김삼웅
Original Assignee
전북대학교산학협력단
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
Priority claimed from KR1020090105152A external-priority patent/KR101146372B1/ko
Application filed by 전북대학교산학협력단 filed Critical 전북대학교산학협력단
Publication of WO2011019134A2 publication Critical patent/WO2011019134A2/fr
Publication of WO2011019134A3 publication Critical patent/WO2011019134A3/fr

Links

Images

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
    • A61K39/02—Bacterial antigens
    • A61K39/025—Enterobacteriales, e.g. Enterobacter
    • A61K39/0275—Salmonella
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61K2039/522—Bacterial cells; Fungal cells; Protozoal cells avirulent or attenuated

Definitions

  • It relates to an attenuated vaccine composition using Salmonella gallinarum mutant strains in which the functions of the lon gene and cpxR gene are impaired.
  • Poultry fever is a contagious disease that causes sepsis in poultry, caused by Salmonella Gallinarum, and is rapidly spreading and high in mortality not only in chicks but also in the chickens. It is a very important disease. Salmonella gallinarum, the causative agent of poultry fever, is characterized by the lack of adequate antibiotics and ineffective treatment. Therefore, it is most appropriate to prevent this disease by using an appropriate vaccine.
  • JOL966 live and dead vaccines have been used, including JOL966 from rough type I, a mutated O-specific chain of lipopolisaccharide (LPS) for laboratory passage. Vaccines also have some protective effects.
  • S-R variation smooth-rough variation
  • the genetic characteristics of JOL966 are not clear, and most of all, there is a possibility that pathogenicity may be restored upon administration to a living body. The risk can be easily estimated by the fact that it is experimentally commonly used to recover pathogenicity by subcultured in artificial medium and administering the attenuated strain back to the living body.
  • lon is an ATP-dependent protease, which is a protease that regulates the host infection mechanism of Salmonella. lon has the effect of inhibiting the expression of invasive genes against SPI1 (salmonella pathogenicity islands), a group of genes involved in invasion of early mesenteric cells. Subsequently, Salmonella typhimurium (SPI2), which stimulates the type III secretion system and has a role in promoting SPI2, a gene involved in the stage of infection that leads to systemic infection and organ colonization through survival and proliferation in macrophages. Salmonella Typhimurium) has been reported in in vitro and in vivo mice (Takaya et al. Infection and Immunity, 2003).
  • CpxA / CpxR acts like autonomic nerves of bacteria. It is a two-component regulator system that is widely known in living organisms for detecting and responding to changes in the external environment. It is thought to be involved. In each role, CpxA is a sensor and cpxR is an activator. Phosphorylation (activation) of CpxR results in envelope stress response system, pilus assembly, type III secretion, motility, chemotaxis, adhesion, biofilm development It is involved in controlling a wide range of reactions.
  • cpxA in Salmonella typhimurium impairs the ability to adhere to macrophages but lacks cpxR, and lack of cpxA or cpxR does not affect survival proliferation in macrophages. Infection in rats has been reported to have no effect on body distribution (Sue Humphreys et al. , Infection and Immunity, 2004). Thus, cpxR deficiency is expected to affect pathogenicity but not inhibit immune formation.
  • Yet another object of the present invention is to provide a feed additive comprising the vaccine composition.
  • the present invention provides a vaccine composition for preventing poultry fever , including Salmonella mutant strains lon and cpxR gene is deleted from the chromosomal DNA of Salmonella.
  • the Salmonella bacteria include Salmonella typhimurium, Salmonella typhi, S. typhi, Salmonella paratyphi, Salmonella Sendai, Salmonella gallinarum, and S. gallinarum. It is preferably selected from the group consisting of Salmonella enteritidis.
  • the vaccine composition may be provided in powder form, for example, for oral administration in a livestock feed, or may be mixed with a suitable preservative for mixing with negative water or for intramuscular injection.
  • the vaccine composition of the present invention is preferably administered by oral, transdermal, intramuscular, intraperitoneal, intravenous, subcutaneous or nasal route.
  • the vaccine composition of the present invention can be administered to poultry such as chickens, ducks, turkeys and quails, and wild birds such as waterfowl and pigeons, and ornamental birds such as canaries to prevent poultry fever.
  • the present invention further provides a feed additive comprising the vaccine composition.
  • the vaccine composition according to the present invention is a live vaccine and is easy to produce and store, it is economical. When administered to poultry, there is no fear of pathogenic return, and it is safer than the existing vaccine because it is superior to existing vaccines. , Safety, and defense are excellent.
  • FIG. 1 is a schematic diagram showing a process of applying Salmonella gallinarum ⁇ lon ⁇ cpxR mutant strain (JOL916) as a chicken Salmonella vaccine.
  • Figure 2 is a weight curve showing the safety of JOL916 vaccination and defense against challenge.
  • 916 (6) IM is the live vaccine vaccine group; -Control challenge without challenge challenge but inoculation; -/-Represents a healthy control with neither inoculation nor challenge.
  • Figure 3 is a diagram showing the cross-immunity to Salmonella gallinarum specific immune and Salmonella typhimurium induced after JOL916 vaccination (transition of plasma IgG).
  • SG uses Salmonella gallinarum antigen
  • ST is Salmonella typhimurium Use of antigens
  • 916 (6) IM was inoculated with JOL916
  • CTRL represents the control.
  • Figure 4 is a diagram showing the cross-immunity to Salmonella gallinarum specific immunity and Salmonella typhimurium induced after JOL916 vaccination (transition of secretion type IgA in the digestive organs).
  • SI represents a stimulation index.
  • Figure 6 shows the survival rate after challenge infection.
  • 916 (6) IM was inoculated with JOL916; -Challenge challenge without vaccination but challenge challenge; -/-Indicates a group that was neither vaccinated nor challenged.
  • Figure 7 shows the diarrhea index after challenge infection.
  • FIG. 9 is a diagram showing the priming index after challenge infection.
  • Figure 10 shows the gross pathological findings in the internal organs after inoculation with a picture showing that JOL916 is now safer than the representative commercialized vaccine JOL966.
  • 916 is the JOL916 inoculation group;
  • 966 is the JOL966 inoculation group;
  • CTRL represents a control.
  • 11 shows plasma IgG following JOL916 and JOL966 vaccination.
  • wpv is weeks post vaccination; 916 is the JOL916 inoculation group; 966 is the JOL966 inoculation group; CTRL represents the control.
  • FIG. 13 is a diagram showing the protection against outdoor strain challenge of JOL 916 in mortality compared with JOL 966.
  • 916IM was inoculated with JOL916; 916PO was orally administered with JOL916; 966IM was inoculated with JOL966; CTRL represents the control.
  • 15 is a diagram showing the defense against the challenge of outdoor strains of JOL916 compared to JOL966 as an appetite index.
  • FIG. 16 is a diagram showing the defense against outdoor strain challenge of JOL916 as a diarrhea index compared to JOL966.
  • 17 is a diagram showing the defense against the challenge of outdoor strains of JOL916 compared to JOL966 as the priming index.
  • 916IM is the JOL916 species inoculation group
  • 916PO is a JOL916 species oral group
  • 966IM represents the JOL966 primary muscle inoculation group.
  • 19 is a diagram showing the protection against outdoor strain challenge of JOL916 compared to JOL966 as the number of isolated strains from the liver.
  • 20 is a diagram showing the protection against outdoor strain challenge of JOL916 compared to JOL966 as the number of outdoor strains isolated from the spleen.
  • FIG. 21 shows pathological findings by dose indicative of safety of JOL916 vaccination in 1 week old chicks.
  • FIG. 22 shows body weight measurements showing safety of JOL916 vaccination in 1 week old chicks.
  • Figure 23 is Salmonella gallinarum specific cellular immunity induced after JOL916 vaccination in 1 week old laying chicks.
  • 25 is Salmonella gallinalum specific plasma IgG concentration induced after JOL916 vaccination in 1 week old hens.
  • Figure 26 is a clinical symptom showing the protection against outdoor strains of JOL916 vaccination in 1 week old chicks.
  • FIG. 27 shows the results of anatomical pathology findings showing protection against outdoor strains of JOL916 vaccination in 1 week old chicks.
  • Salmonella gallinarum outdoor strain JOL394 (Table 1) lon The 5 'and 3' ends of the gene were amplified by PCR using lon-F-XbaI and lon-R-XhoI, lon-F-XhoI and lon-R-XbaI as primers, respectively.
  • ® Cloned to -T vector (PromegaCo., Wi, USA) (Table 2).
  • digestion was performed with restriction enzyme XhoI and ligation to obtain a gene sequence in which the lon gene was deleted. This sequence was cleaved with XbaI and cloned into a suicide vector pMEG375 (by Dr. Curtiss R. III.
  • pBP294 Dozoisetal., 2003 to obtain pBP294.
  • a suicide vector pBP210 having a sequence deleted with the cpxR gene was obtained. Deletion of the full length lon gene and full length cpxR gene was confirmed from the sequences of pBP294 and pBP210.
  • E.coli ⁇ 7213 is transformed with pBP294 and pBP210, respectively.
  • E.coli s was incubated with LB culture medium to which 50ng / ml of DL- ⁇ , ⁇ -diaminopimelic acid (DL- ⁇ , ⁇ -Diaminopimellicacid, DAP, Sigma) was added.
  • DL- ⁇ , ⁇ -Diaminopimellicacid DAP, Sigma
  • coli with pBP294 was introduced into JOL394 in LB-DAP agar by conjugation to delete the lon gene in Salmonella gallinalum JOL394. Since JOL394 was unable to supply the ⁇ -protein, pBP294 failed to replicate and did not persist and naturally disappeared when it was not introduced into the chromosome. At the same time, resistant bacteria were selected from LB agar to which 50 ⁇ g / ml ampicillin was added using only those bacteria to which pBP294 was introduced showed antibiotic resistance. These selected colonies were incubated in LB liquid medium without antibiotics at 600 nm to have an absorbance of 0.5 to 1.0, and then diluted appropriately and selected in a medium containing sucrose in LB.
  • the DNA of pBP294 is a sucrose-sensitive gene sacB Because of the presence of a host that continues to retain this gene (with a plasmid), only the host with the missing gene (plasmid) is viable. Selected colonies were again cultured by tooth-picking in LB / sucrose agar and LB / ampicillin agar, and colonies that grow in LB / sucrose agar and do not grow in LB / ampicillin agar were selected as mutated strains, S. Gallinarum ⁇ lon (JOL914). The selected strains were identified for mutation through PCR. to the next S . ⁇ cpxR was introduced into Gallinarum ⁇ lon strains using the same conjugation and selection method. S . Gallinarum ⁇ lon ⁇ cpxR (vaccine strain) was obtained.
  • Nal nalidixic acid
  • Cm Chloramphenicol
  • Ap ampicillin
  • Salmonella mutant strain JOL916 was suspended in Tryprose Soybean Broth (TSB) with 20% glycerol and stocked at -80 degrees.
  • the stock was inoculated in TSA (Tryptose Soybean Agar) solid medium, incubated at 37 ° C for 16 hours, inoculated again in TSA, and cultured under the same conditions three times in total to obtain an S-type colony.
  • TSA Tryprose Soybean Agar
  • One colony was inoculated into TSB and cultured for 16 hours in a shaking incubator (200 rpm, 37 ° C) was added to TSB at a ratio of 1/100 (volume), and the concentration was 10 9 cfu (colony forming unit) in the incubator.
  • the culture solution was centrifuged at 4,000 rpm at 4 ° C., washed three times under the same conditions with PBS (Phosphate buffered saline), and the OD 600 values were measured.
  • the concentration was appropriately diluted or concentrated to inoculate the live vaccine.
  • the cells were resuspended in 1% formalin-added PBS at an appropriate concentration and inactivated at 4 ° C. for 24 hours.
  • the route of administration may be intramuscular or subcutaneous injection and oral administration. In this case, 2 ⁇ 10 6 cfu was inoculated into the muscle to observe the presence of side effects, immunity, and defense against outdoor strains.
  • the bacterial count count was performed after colony count method (overnight incubation, 37 °C) in TSA, the relationship between the OD 600 value is as follows. However, C is the number of bacteria (unit: ⁇ 10 9 cfu) by the colony measurement method, OD 600 is OD 600 value.
  • JOL916 strain Salmonella gallinarum mutant strain obtained by Example 2
  • 2 ⁇ 10 6 cfu / 100 ⁇ l was inoculated intramuscularly (IM) into 5 week old laying chicks.
  • IM intramuscularly
  • the body weight was measured by 3-4 days when the side effects started to occur, 6-7 days when the recovery started, and 10 days after the recovery, and the presence or absence of side effects caused by the inoculation was examined (Table 3). .
  • IM intra-muscular inoculation
  • cfu colony forming unit
  • LPS was isolated from outdoor strains JOL420 (Salmonella gallinarum outdoor strain) and JOL389 (Salmonella typhimurium outdoor strain) using LPS extraction kit (Intron Biotechnology, Korea) and these antigens were isolated from a flat bottom 96 well high binding ELISA plate (flat). Adsorbed onto a bottom 96 well high binding ELISA plate, Greiner, Germany, the chicken IgG (or IgA) ELISA quantification kit (quantitation kit, Bethyl, Tx, USA) was used following the instructions.
  • Example 3 Samples are given in Example 3 The samples were taken from the same chick, plasma was isolated from heparin-added peripheral blood and digestive tract lavage was obtained by the following method (Berthelot-Herault et al., Vet Immunol Immunopathol, 2003). That is, the washing liquid (48.5 mM PEG [polyethylene glycol 3350], 40mM Na 2 SO 4 , 20mM NaHCO 3 , 30 mM NaCl) orally administered 12 ml / kgBW (body weight) 30 minutes after pilocarpine (pilocarpine) at a dose of 13mg / kgBW (20mg / kgBW for BW ⁇ 300 g) Inject muscle.
  • the washing liquid (48.5 mM PEG [polyethylene glycol 3350], 40mM Na 2 SO 4 , 20mM NaHCO 3 , 30 mM NaCl) orally administered 12 ml / kgBW (body weight) 30 minutes after pilocarpine (
  • STI / EDTA solution 0.1 mg soybean trypsin inhibitor in 50 mM EDTA, pH 8.0
  • the effluent is recovered and 10 ⁇ l of 100 mM PMSF (phenylmethylsulfonyl fluoride) is added per 1 ml, followed by centrifugation (13,000 rpm, 2 min, 4 ° C.) to obtain a clear supernatant.
  • PMSF phenylmethylsulfonyl fluoride
  • BSA bovine serum albumin
  • Peripheral lymphocyte differentiation measurements are described in Barta et al. (Avian Dis, 1992) .Refer to the research results, and centrifuged 0.8 ml of heparinized blood at 40 rpm ( ⁇ 10 rcf) at room temperature for 10 minutes to recover mononuclear leukocytes with plasma and added antibiotics and fetal bovine serum. After washing and resuspending with a RPMI1640 complete medium, the cell number was adjusted to 1 ⁇ 10 5 cfu / ml after confirmation of the number of living cells by trypane blue exclusion test.
  • the mutant strain induces immunity to Salmonella typhimurium at the same time as the specific immunity to Salmonella gallinarum.
  • Example 5 ⁇ JOL916 strain confirms the defense of the live vaccine
  • Salmonella gallinarum outdoor strain JOL422 was inoculated (2x10 6 cfu) by muscle inoculation (challenge infection) as compared to the defense ability.
  • control group for the vaccinated group was compared with the non-vaccinated group (-/ challenge) and the healthy control group without vaccination or challenge (-/-).
  • Vaccination group showed a survival rate of 100% with a healthy control group not vaccinated neither vaccine nor outdoor strain after challenge challenge (Fig. 6).
  • the vaccinated group showed acute and severe clinical symptoms after challenge, and all died, but the JOL 916 vaccinated group showed mild clinical symptoms with slight weight loss up to 6 days, and none were inoculated.
  • IM intra-muscular
  • cfu colony forming unit
  • mice were euthanized each week to observe gross pathological findings.
  • lesions such as enlargement, white spots, and soft (liver) were evaluated, and they were classified according to the individual organ lesions by 0 points (normal), 1 point, 2 points, and 3 points (very severe).
  • JOL916 was determined to be more safe than JOL966.
  • JOL916 is believed to be alive faster than JOL966. JOL916 may also remain slightly in the spleen at 4 weeks, but emphasizes that it does not in itself represent pathogenic manifestations. In other words, if there is no problem in the state of health, weight ratio, and pathology, it is reasonable to consider that it is an immunogenic source.
  • plasma IgG measurement was measured by ELISA in the same manner as in Example 3 by separating the outer membrane protein (outer membrane protein) fraction from the outdoor strain of Salmonella gallinarum (Fig. 11). Intestinal S-IgA measurement was performed by removing 10 cm of the crop and ileum, washing with PBS containing the same additive as in Example 3, centrifuging, and measuring the result by ELISA. .
  • the mortality and clinical symptoms were assessed and compared after challenge. Mortality reached 100% in the vaccinated group and 10% in the JOL966 vaccinated group by day 12 (FIG. 13).
  • the growth curve is a curve excluding the dead individuals in the JOL966 group, but the JOL916 inoculation group shows the best growth rate (FIG. 14).
  • the weight gain was reduced shortly after challenge but gradually recovered.
  • the control group was stopped due to death.
  • the clinical symptoms were severely worsened in the control group and died.
  • the JOL 966 inoculated group recovered with clinical symptoms such as weak depression in up to 5 animals after challenge.
  • the JOL 916 inoculated group was weaker than the JOL 966 inoculated group. Only one symptom was shown (FIGS. 15-17).
  • JOL 916 prepared as in Example 2, 10 6 cfu / 100 ⁇ l, 10 7 cfu / 100 ⁇ l, 10 8 cfu / 100 ⁇ l, 10 9 cfu / 100 ⁇ l, 10 10 cfu / 100 ⁇ l 1 week old chick (Brown Nick Oral administration to 20 rats at each concentration, and for comparison, 10 5 cfu / 100 ⁇ l, 10 6 cfu / 100 ⁇ l, 10 7 cfu / 100 ⁇ l, 10 8 cfu / 100 ⁇ l, 10 9 cfu 20 animals were orally administered in the same manner. The mortality was checked for 3 weeks to calculate the 50% lethal dose (LD 50 ).
  • LD 50 50% lethal dose
  • the animals were examined by gross euthanasia after euthanasia. Lesions of the individual organs with 0 (normal), 1, 2, and 3 (very severe) lesions were evaluated in the liver and spleen by assessing lesions such as enlargement, white spots, and softening of the liver. Classification was evaluated by. As a result, the pathogenicity was significantly reduced compared to the outdoor strain, and especially when inoculated with 2.0 X 10 6 cfu, pathological findings were not observed at all visually (FIG. 21).
  • OMP Outer membrane protein
  • JOL422 soluble antigen-specific immune responses.
  • OMP was obtained by Modified lysozyme-osmotic shock method. Centrifuge (7000 g, 10 min, 4C) 150 ml of culture to obtain pellets. Lysozyme was added (400 ⁇ l of 4 mg / ml) by resuspension in 800 ⁇ l of 100 mM Tris-HCl (500 mM sucrose, 0.5 mM EDTA, pH8.6).
  • the feed for measuring immune response was collected as follows. Peripheral lymphocytes and plasma were centrifuged with 0.8 ml of heparinized blood at 40 rpm ( ⁇ 10 rcf) at room temperature for 10 minutes to recover mononuclear leukocytes with plasma and added RPMI1640 complete media with antibiotics and fetal bovine serum. After washing, resuspending and confirming the number of living cells by trypane blue exclusion test (trypane blue exclusion test) was adjusted to 1 ⁇ 10 5 cfu / ml. Plasma was obtained by centrifugation at 1500 rpm for 5 minutes and stored in a freezer (-20 ° C).
  • the small intestine wash was excised to a specific length of the small intestine 10 cm in length and washed with 1 ml of PBS to centrifuge the wash solution (13,000 rpm, 2 min, 4 °C) to obtain a clear supernatant. 10 ⁇ l of 100 mM PMSF, 1% Sodium azide, and 5% BSA (bovine serum albumin) were added to the supernatant, respectively, and stored at 4 ° C. to be used as samples of the next day ELISA.
  • Peripheral lymphocytes proliferation assay was performed to measure cellular immune response (Barta et al., 1992, Avian Dis). 100 ⁇ l of cell suspension per well and 50 ⁇ l of 0.1 ⁇ g / ml aqueous antigen solution (Rana et al, 2006) in a 96-well plate (control wells RPMI-1640) at 40 ° C. in the presence of 5% CO 2 . Incubated for 40 hours.
  • the cells were treated with the ViaPlus assay kit (Lonza, USA) to measure the luminescence, and the ratio of the values of wells stimulated with specific antigens and those of control wells with RPMI-1640 instead of antigens were measured using the Stimulation index (SI). It was calculated as and compared by group.
  • SI Stimulation index
  • IgG in plasma and IgA in small intestine wash were subjected to indirect ELISA using OMP as antigen.
  • Antigen was adsorbed onto a flat-bottom 96 well high binding ELISA plate (Greiner, Germany) to use a chicken IgG (or IgA) ELISA quantification kit (Bethyl, Tx, USA).
  • the cellular immunity by JOL916 showed an excellent response similar to the response by JOL394 (Fig. 23).
  • IgA response in the gut was weaker than the reaction by JOL394 but showed a specific reaction (FIG. 24).
  • the plasma IgG concentration showing the systemic immune response showed an excellent response in the JOL916 inoculation group (FIG. 25).
  • the present invention is industrially available as a vaccine composition for preventing poultry typhoid including salmonella mutant strains in which Ion and cpxR genes are deleted, or as a feed additive comprising the vaccine composition.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente invention concerne une composition vaccinale comprenant des variants de micro-organismes de Salmonella, dont les gènes lon et cpxR sont effacés de l’ADN dans les chromosomes de ceux-ci, pour la prévention de la typhoïde aviaire. Le vaccin de salmonelle atténuée selon la présente invention est un vaccin vivant facilitant la production et le stockage économique. Etant donné qu’il est exempt du risque récurrent de pathogénicité, le vaccin peut être administré sans risque à la volaille. En outre, la résistance de protection du vaccin contre des souches sauvages est supérieure à celle des vaccins classiques.
PCT/KR2010/003233 2009-08-11 2010-05-24 Composition vaccinale comprenant des variants de micro-organismes de salmonella pour la prévention de la typhoïde aviaire WO2011019134A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2009-0073973 2009-08-11
KR20090073973 2009-08-11
KR10-2009-0105152 2009-11-02
KR1020090105152A KR101146372B1 (ko) 2009-08-11 2009-11-02 살모넬라 변이균주를 포함하는 가금티푸스 예방용 백신 조성물

Publications (2)

Publication Number Publication Date
WO2011019134A2 true WO2011019134A2 (fr) 2011-02-17
WO2011019134A3 WO2011019134A3 (fr) 2011-04-21

Family

ID=43586596

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2010/003233 WO2011019134A2 (fr) 2009-08-11 2010-05-24 Composition vaccinale comprenant des variants de micro-organismes de salmonella pour la prévention de la typhoïde aviaire

Country Status (1)

Country Link
WO (1) WO2011019134A2 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020077272A1 (en) * 1999-02-02 2002-06-20 Mahan Michael J. Reducing bacterial virulence
US7045122B2 (en) * 2000-11-16 2006-05-16 Akzo Nobel N.V. Salmonella vaccine
KR20080082156A (ko) * 2007-03-07 2008-09-11 전북대학교산학협력단 ｌｏｎ 유전자 및／또는 ｃｐｘＲ 유전자가 결실된살모넬라 변이균주 및 이를 함유하는 살모넬라 생백신
US20080220022A1 (en) * 2006-12-11 2008-09-11 Francois-Xavier Le Gros Salmonella Vaccine

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020077272A1 (en) * 1999-02-02 2002-06-20 Mahan Michael J. Reducing bacterial virulence
US7045122B2 (en) * 2000-11-16 2006-05-16 Akzo Nobel N.V. Salmonella vaccine
US20080220022A1 (en) * 2006-12-11 2008-09-11 Francois-Xavier Le Gros Salmonella Vaccine
KR20080082156A (ko) * 2007-03-07 2008-09-11 전북대학교산학협력단 ｌｏｎ 유전자 및／또는 ｃｐｘＲ 유전자가 결실된살모넬라 변이균주 및 이를 함유하는 살모넬라 생백신

Also Published As

Publication number Publication date
WO2011019134A3 (fr) 2011-04-21

Similar Documents

Publication Publication Date Title
EP0500699B1 (fr) Vaccins de protection croisee contre la salmonella
US6656478B1 (en) Cross-protective salmonella vaccines
AU2001256957B2 (en) Salmonella vaccine materials and methods
WO2012157989A2 (fr) Souches modifiées avirulentes de salmonella gallinarum et composition pharmaceutique utilisant celles-ci
AU2001256957A1 (en) Salmonella vaccine materials and methods
KR101150318B1 (ko) 이. 콜라이 및 살모넬라에 대한 조류 배합 백신
WO2018124407A1 (fr) Composition de vaccin contenant un mutant de salmonelle atténuée utilisé comme principe actif pour prévenir ou traiter simultanément une entéropathie proliférative porcine et la salmonelle
Tan et al. Evaluation of an aroA mutant Salmonella typhimurium vaccine in chickens using modified semisolid Rappaport Vassiliadis medium to monitor faecal shedding
KR101146372B1 (ko) 살모넬라 변이균주를 포함하는 가금티푸스 예방용 백신 조성물
WO2005001069A1 (fr) Marqueur genetique pour vaccins bacteriens vivants
Senevirathne et al. Prospective lipid-A altered live attenuated Salmonella Gallinarum confers protectivity, DIVA capability, safety and low endotoxicity against fowl typhoid
WO2013015586A9 (fr) Composition de vaccin destinée à prévenir et à traiter la colibacillose et la salmonellose chez la volaille, contenant une souche de salmonelle exprimant des facteurs de virulence pathogènes d'escherichia coli de volaille
WO2013165190A1 (fr) Vaccin pour la prévention de la septicémie hémorragique virale des poissons plats
WO2011019134A2 (fr) Composition vaccinale comprenant des variants de micro-organismes de salmonella pour la prévention de la typhoïde aviaire
Barrow et al. Control of food-poisoning salmonella in poultry–biological options
Wigley et al. Salmonella in preharvest chickens: current understanding and approaches to control
US6491910B1 (en) Ovo administration of a competitive exclusion culture
US20020012672A1 (en) Live vaccine against colibacillosis
KR20120129777A (ko) 약독화, 면역강화 살모넬라 엔테리티디스의 변이균주를 포함하는 살모넬라증 예방용 생균 백신 조성물
KR20220167577A (ko) FliC-FimA-CD40L 융합 항원을 발현하는 살모넬라 갈리나룸 변이주를 유효성분으로 포함하는 가금티푸스 및 살모넬라증 동시 예방 또는 치료용 백신 조성물
WO2017150755A1 (fr) Composition de vaccin trivalent inactivé contre les salmonelles à niveau réduit d'endotoxines pour la prévention de la typhoïde aviaire et de la salmonellose
WO2013147534A1 (fr) Composition de vaccin contre la typhoïde aviaire utilisant un immunostimulant vivant
WO2022231043A1 (fr) Souche atténuée de salmonella gallinarum et son utilisation
KR101481119B1 (ko) 고스트 살모넬라균주 및 이를 유효성분으로 포함하는 가금 살모넬라증 예방용 백신 조성물
Barrow Salmonella infections and vaccines

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10808283

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10808283

Country of ref document: EP

Kind code of ref document: A2