EP1023083A1 - Vaccins veterinaires - Google Patents

Vaccins veterinaires

Info

Publication number
EP1023083A1
EP1023083A1 EP98949828A EP98949828A EP1023083A1 EP 1023083 A1 EP1023083 A1 EP 1023083A1 EP 98949828 A EP98949828 A EP 98949828A EP 98949828 A EP98949828 A EP 98949828A EP 1023083 A1 EP1023083 A1 EP 1023083A1
Authority
EP
European Patent Office
Prior art keywords
vaccine
clostridium
antigens
vaccine composition
vaccines
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.)
Withdrawn
Application number
EP98949828A
Other languages
German (de)
English (en)
Other versions
EP1023083A4 (fr
Inventor
Richard Buchta
Christopher Leigh Schwartzkoff
Philip Ralph Lehrbach
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wyeth
Original Assignee
Fort Dodge Australia Pty 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
Priority claimed from GBGB9722035.4A external-priority patent/GB9722035D0/en
Application filed by Fort Dodge Australia Pty Ltd filed Critical Fort Dodge Australia Pty Ltd
Publication of EP1023083A1 publication Critical patent/EP1023083A1/fr
Publication of EP1023083A4 publication Critical patent/EP1023083A4/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K39/08—Clostridium, e.g. Clostridium tetani
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • 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
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59

Definitions

  • the present invention relates to novel vaccine compositions for parenteral administration, methods for their use and to processes for their preparation.
  • naive ⁇ o animals ie. animals which have not been previously vaccinated
  • naive ⁇ o animals are treated in a two stage dose regime consisting of an initial dose and a second booster dose several weeks later.
  • the action of the booster dose raises the antibody titre to a level that may sustain protection from a disease causing challenge organism for an extended period. Animals undergoing this vaccination program are usually mustered each year for revaccination.
  • aluminium based vaccines have been found to have relatively short duration of protection while water-in-oil emulsion vaccines have a longer duration of protection but have been found to be unsuitable for use because they cause unacceptable lesions at the injection sites of the animals ('Experimental Clostridial Oil Emulsion Vaccines' Thomson RO. and Batty I., Bull. Off. int Epiz. 1967
  • WO 91/00106 discloses multi-phase emulsions suitable for administering active substances or antigens by injection of the water in oil in water type. These emulsions are produced from
  • oils contained in the emulsions include mineral, vegetable or animal oils, and synthetic hydrocarbons. It was observed that these vaccines were well tolerated in pigs and did not cause any local reactions, abscesses or necroses. However, no data were provided regarding the oils contained in the emulsions.
  • the applicants provide vaccines which are suitable for the prevention of clostridial diseases of sheep and in particular lambs, providing an effective immunity for up to a year or more following a single injection or dose. Therefore, the present invention addresses the problems associated with known vaccines, providing a level of effective immune response in sheep for the period of approximately one
  • the present invention also provides vaccines which provide an effective immunity against each of a number of diseases for up to a year or more following a single injection or dose of a multivalent vaccine.
  • the selection of an adjuvant which enhances the antigenic response to clostridial antigens in sheep is thus a problem addressed by the invention.
  • the selection of an adjuvant which enhances the antigenic response to each of a number of micro-organisms in sheep is a particular problem addressed by the invention.
  • a sheep vaccine composition comprising: a) an oily adjuvant acceptable for veterinary purposes comprising: i) a white mineral oil having a molecular weight of about 250 to 300 and ii) a mannitol oleate emulsifier and b) an aqueous phase comprising one or more clostridial antigens.
  • the vaccine composition is an injectable emulsion of the water in oil type and preferably has a viscosity of about 200mPas or less, more preferably about lOOmPas to about 150mPas.
  • the white mineral oil is preferably between about 50% and about 70% by weight of the emulsion more preferably between about 53% and about 63% by weight of the emulsion.
  • the mannitol oleate emulsifier is preferably between about 2% and about 10% by volume of the emulsion more preferably between about 3% and about 7%.
  • the white mineral oil has a molecular weight of about 250 to 300, preferably about 270 to 290, more preferably about 280.
  • the oil is preferably one which is liquid at 4°C and has a viscosity lower than lOOmPas at 25°C. It preferably has a density at 20°C of about 815 to 840kg/m 3 , more preferably about 817 to 837kg/m 3 .
  • the dynamic viscosity of the oil at 25°C is preferably about 5 to 15mPas, more preferably about 6 to 13mPas.
  • the oil preferably has a kinematic viscosity at 40°C of about 5 to 10mm 2 /s, more preferably about 7.5mm 2 /s.
  • Preferred embodiments of the invention include the commercially available oil Marcol 52 which is supplied by ESSO.
  • the mannitol oleate emulsifier is preferably an anhydromannitol ether octadecanoate.
  • Preferred emulsifiers have a viscosity at 25°C of about 300 to 400cP, more preferably about 340 to about 360cP, particularly preferred embodiments are those in which the emulsifier has a viscosity of about 350cP.
  • the emulsifier preferably has a specific gravity at 20°C of about 0.8 to 1.0, more preferably of about 0.95 to about 0.99, particularly suitable are those with a specific gravity at 20°C of about 0.97.
  • Particularly preferred emulsifiers are those with a refractive index at 25°C of about 1.4 to 1.5, more preferably of about 1.47 to 1.48, particularly those with a refractive index at 25°C of about 1.4748 to 1.4758.
  • Particularly preferred oils are the commercially available ones Montanide 80, Montanide 103 and Montanide 888 supplied by SEPPIC SA, 75 Quai D-Orsay, 75007 Paris. Montanide 103 and Montanide 888 being more preferred and Montanide 888 being most preferred.
  • the proportion of oily adjuvant to aqueous phase included in the emulsion can be adjusted to optimise vaccines including particular antigens and for use in particular animals. It can also be modified to optimise vaccines for administration at a particular site.
  • the site of administration may also affect the efficacy and/or the site reactions caused by the vaccines.
  • the site of administration can be selected so as to optimise the effects of vaccines including particular antigens and for use in particular animals.
  • the vaccines exemplified herein were found to be efficacious regardless of site of administration, however site reactions from the exemplified vaccines were more numerous when they were administered at the brisket.
  • Clostridial antigens suitable for use in the compositions of the present invention include Clostridium perfringens type A, B, C and D, Clostridium septicum, Clostridium tetani, Clostridium chauvoei, Clostridium novyi type B, Clostridium sordelli, Clostridium haemolyticum, Clostridium chauvoei and o Clostridium botulinum C and D.
  • Suitable antigens include those which are useful in the treatment of diseases such as Lamb dysentery, Pulpy Kidney disease (enterotosemia), Malignant Oedema (blood poisoning), Tetanus, Blackleg disease and Black disease.
  • Antigens suitable for use in the present invention are any which provide a suitable immune response, eg. toxoids or anacultures.
  • Suitable antigens include Clostridium perfringens A, B, C and D toxoids; s Clostridium novyi B toxoid; Clostridium chauvoei anaculture; Clostridium septicum toxoid, Clostridium tetani toxoid and Clostridium sordelli toxoid.
  • the vaccine is preferably a multi-valent vaccine, ie. a vaccine providing protection against a number of different clostridial diseases by incorporating a number of different clostridial antigens eg. the vaccine may contain any number of antigens selected from the list provided above. It is particularly o useful to provide a multivalent vaccine, ie. one which provide adequate immune response to a number of pathogens to increase the protection provided by the vaccine. It is particularly difficult to provide multivalent vaccines because it is necessary to provide a vaccine which induces an adequate antigenic response to all the micro-organisms of interest. Thus the threshold antibody responses are described in compendial standards (eg. Australian Therapeutic Goods order No.
  • Preferred embodiments of the invention are vaccines comprising at least two types of clostridial antigen, each one being active against any one of the following: Clostridium perfringens; Clostridium 0 novyi; Clostridium chauvoei; Clostridium septicum and Clostridium tetani. Particularly preferred embodiments being vaccines comprising an antigen to all five diseases listed.
  • Particular embodiments are vaccines comprising at least two of the following types of clostridial antigen: Clostridium perfringens D toxoid; Clostridium novyi B toxoid; Clostridium chauvoei anaculture; Clostridium septicum toxoid and Clostridium tetani toxoid.
  • a particularly preferred embodiment being a 5 vaccine comprising all five antigens listed.
  • the vaccine may also comprise antigens against other diseases eg. Pasteurella antigens such as Pasteurella maltocida and Pasteurella haemolyticum; Corynebacterium antigens such as Corynebacterium pseudotuberculosis, Corynebacterium renale, Corynebacterium cystitis and Corynebacterium pilosum; and Haemophilus antigens such as Haemophilus somnus and Haemophilus pleuropneumoniae; Mycoplasma antigens such as Mycoplasma agalactiae and Mycoplasma ovipneumoniae.
  • Pasteurella antigens such as Pasteurella maltocida and Pasteurella haemolyticum
  • Corynebacterium antigens such as Corynebacterium pseudotuberculosis, Corynebacterium renale, Corynebacterium cystitis and Corynebacterium pilosum
  • Haemophilus antigens such
  • Corynebacterium antigens such as Corynebacterium pseudotuberculosis, Corynebacterium renale, Corynebacterium cystitis and Corynebacterium pilosum.
  • a particularly preferred embodiment of the invention comprises antigens of Clostridium perfringens D toxoid; Clostridium novyi B toxoid; Clostridium chauvoei anaculture; Clostridium septicum toxoid, Clostridium tetani toxoid and Corynebacterium pseudotuberculosis.
  • the invention particularly relates to vaccines comprising one or more Clostridial antigens in o combination with one or more non-Clostridial antigens.
  • Co-adjuvants may optionally be included in the vaccines of the present invention.
  • the antigens may be in the form of toxoids or cell antigens but if cell antigens are used a co-adjuvant may be required.
  • Such co-adjuvants may suitably include a saponin (eg. quil A) or cytokines such as Interleukin- 1 , 2, and 4 or muramyl dipeptide.
  • emulsifiers such as dioctyl decyl ammonium bromide (DDA) may s also be included in the vaccines if desired.
  • the vaccine composition of the present invention may contain one or more antigens and one or more emulsifiers and/or one or more co-adjuvants. Supplements such as selenium which is important for growth and reproductive processes may also be included in the vaccine.
  • Vaccines according to the present invention may be prepared by dissolving antigens in a suitable o aqueous medium such as normal saline, stirring the resultant mixture and adding it to a suitable oil phase, The mixture is then stirred (eg. at 200 to 600rpm) and/or homogenised (eg.
  • the vaccines of the invention can provide a sustained and elevated immune response when administered to the target animals, sheep, in a single dose. They are preferably capable of inducing a response which can be measured, eg., by ELISA or SN neutralisation titres, for a period of at least 12 months.
  • the vaccine compositions of the present invention are stable and may be stored for several months or even years without loss of antigenic potency.
  • the vaccines o are capable of overcoming maternal antibody.
  • Example 1 Preparation and efficacy of a single dose clostridial plus Corynebacterium pseudotuberculosis 6-in-1 5 vaccine for use in sheep
  • compositions were prepared according to Table I below.
  • the compositions were initially prepared by mixing Clostridial and Corynebacterium pseudotuberculosis antigens with normal saline and thiomersal at room temperature to prepare the aqueous phase of the vaccines.
  • the pH of the aqueous phase being between pH7 and pH7.5
  • For composition 1 the aqueous phase was added to a mixture of Marcol 52 and Montanide 888 (ratio 10.7 to 1 pre-equilibrated to room temperature). This mixture was then homogenised to create a water-in-oil emulsion (viscosity ⁇ 200mPas).
  • the dose volume of Composition 1 was 1mL.
  • Composition 2 was prepared in a similar manner except that an aluminium based adjuvant, Tasgel was added instead of the Marcol 52/Montanide 888 mixture.
  • the aqueous phase/Tasgel mixture was stirred at 100 to 600rpm at room temperature for 15 minutes and the pH adjusted with HCI to pH 6.5 ⁇ 0.3.
  • the dose volume of Composition 2 was 2mL
  • the efficacy of the vaccines was tested using a group of thirty approximately four year old pregnant ewes (first cross Border-Leicester) identified by ear tags.
  • the ewes were vaccinated subcutaneously with the vaccines described above approximately two to three weeks prior to the onset of lambing. Twenty lambs born to the previously vaccinated ewes were vaccinated by subcutaneous injection of the vaccine compositions.
  • the vaccine regimes are shown below in Table II:
  • Lambs were at least eight weeks old when vaccinated. Only Group 5 received a second vaccination at Week 4, these animals were vaccinated with 6 in 1 vaccine comprising Tasgel as adjuvant. Serum samples were collected from blood centrifuged for 15 minutes at 3000rpm and at room temperature. The following assays were performed on serum samples: CI. perfringens D ELISA was performed on individual serum samples using purified rabbit anti-CI. perfringens epsilon toxin diluted in carbonate buffer pH9.6 in a 96 well microtitre plate. This was incubated at 37°C for 2h before purified CI.
  • perfringens toxin diluted in phosphate buffered saline/Tween 20 (0.1%w/v) was added and the plate incubated at 37°C for 1h.
  • Dilutions of sheep sera (and positive and negative sera) were added to the wells and the plate incubated for 1 h at 37°C.
  • the plates were then washed with PBS/Tween and a dilution of rabbit anti-sheep IgG horseradish peroxidase conjugate (Biorad) in PBS/Tween added.
  • Biorad rabbit anti-sheep IgG horseradish peroxidase conjugate
  • Activated substrate (2,2-azino-di-3- ethylbenzthiazolinosulfonate) dissolved in citrate phosphate buffer pH4.6 at 1 mg/mL and activated by addition of 073% hydrogen peroxide was added to the plate. Absorbance at 405nm was read after 30 to 60 minutes using a Titertek Multiscan reader.
  • mice serum neutralisation titres of pooled group sera for CI. novyi , CI. tetani,, CI. septicum and CI. perfringens D were carried out according to the Therapeutic Goods Order No. 30 (Australian
  • Corynebacterium pseudotuberculosis (C. pseudotuberculosis) serum neutralisation titres were determined for individuals and pooled sera samples based on observations by Muckel & Giles, Am. J.
  • brackets represent the number of lambs with site reactions/number of lambs per group.
  • the results displayed are the GMT of individual titres for that group.
  • Vaccination of lambs in Group 7 with the single dose M52-M888 adjuvanted vaccine indicated that maternal antibody could be overcome by providing a response to vaccination, when compared to the standard (Group 5). Comparing non- vaccinates with vaccinates (Groups 4 and 5 or groups 6 and 7) maternal antibody appeared to decline to a level below the sensitivity of the ELISA by Week 4 following marking. The 95% confidence intervals of the mean for each group indicate that from Week 8 onwards only Group 7 has a statistically significantly higher titre than all other groups (p O.05).
  • the capacity of a single dose of the M52-M888 adjuvanted vaccine to generate responses is at least as good as the two dose o vaccine. Furthermore the M52-M888 adjuvanted vaccine was administered in a single dose.
  • Example 2 Preparation and efficacy of a single dose clostridial 5-in-1 vaccine for use in sheep Vaccine compositions used in this example were prepared in a similar manner to the compositions described above in Example 1 (see Table I) except that the C. pseudotuberculosis antigen was s omitted. Selenium (1 mg per dose) was added to the aqueous phase prior to mixing with either Marcol 52/Montanide 888 or Tasgel.
  • Fine wool Merryville Merino ewes and lambs were vaccinated subcutaneously in the left side of the neck in accordance with the regime set out below in Table X. They were vaccinated on the right side of the neck when a second and/or booster dose was required. o All these lambs were derived from Merino ewes that had been previously vaccinated with 5 in 1 Tasgel vaccine 1 month prior to lambing.
  • Lambs were vaccinated when four to eight weeks old. Groups 2 and 3 were vaccinated with a second dose of 5 in 1 Tasgel vaccine at week 4. Groups 2,3,4 and 5 received a booster vaccination with the 5 respective vaccinates for the group at week 51.
  • Serum samples were collected from blood centrifuged at 3000rpm, 15min at room temperature. The assays described above in Example 1 were performed on the serum samples.
  • M52-M888 adjuvanted vaccine formulation (Group 4 ) was used in a single dose regime compared to a two dose regime for the gel formulations (Groups 2 and 3).
  • the addition of selenium did not offer any immunological advantage, although it is known to act as an immune stimulant. It is primarily added as a mineral supplement to these vaccines.
  • SN Titres in Lambs 5 SN titres for CI. perfringens D, CI. tetani, CI. septicum and CI. novyi B were determined for selected pooled group sera samples from Groups 1 to 5.
  • the vaccines were assessed in the standard rabbit potency test (Therapeutic Goods Order No. 30 Australian Government Publishing 1987). A summary of results is presented in Table XIV.
  • the vaccine formulation of 5 in 1 M52-M888 adjuvanted vaccine formulation (Group 4) passed potency in all fractions, following a single dose vaccination. This result was similar to that of the standard gel vaccine following two doses (Group 2).
  • the vaccines with selenium (Groups 3 and 5) were not assessed in the rabbit potency test,
  • the CI. chauvoei guinea pig challenge test is a regulatory requirement (Therapeutic Goods Act, 1966, Therapeutic Goods Order No. 30). Vaccines with a CI. chauvoei fraction must pass this test in order to be released for use.
  • a pass in the challenge test is at present defined as: "10 out of 10 guinea pigs vaccinated with two doses (4 weeks apart) of an aluminium hydroxide adjuvanted clostridial vaccine, surviving a CI. chauvoei challenge at 2 weeks post second vaccination for 5 days post challenge". This result is compared with non-vaccinated controls which must succumb to challenge within 3 days.
  • the vaccines were assessed in the CI. chauvoei guinea-pig challenge test and the results of the challenge tests are shown below in Table XVI.
  • single dose vaccine is more efficacious and provides a sustained immune response to the clostridial antigens as determined by ELISA and SN tests.
  • the single dose vaccine is safe, with negligible site reactions and passed the rabbit potency test in all fractions (CI. perfringens D, CI. tetani, CI. septicum, CI. novyi B and CI. chauvoei). and the guinea pig CI chauvoei challenge test,

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

Abstract

L'invention concerne des vaccins vétérinaires qui sont destinés à la prévention de maladies clostridiales affectant les moutons (et agneaux) et qui assurent une immunité efficace pendant au moins un an après une seule injection ou dose.
EP98949828A 1997-10-17 1998-10-16 Vaccins veterinaires Withdrawn EP1023083A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB9722035 1997-10-17
GBGB9722035.4A GB9722035D0 (en) 1997-10-17 1997-10-17 Veterinary vaccines
PCT/AU1998/000865 WO1999020305A1 (fr) 1997-10-17 1998-10-16 Vaccins veterinaires

Publications (2)

Publication Number Publication Date
EP1023083A1 true EP1023083A1 (fr) 2000-08-02
EP1023083A4 EP1023083A4 (fr) 2006-06-14

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP98949828A Withdrawn EP1023083A4 (fr) 1997-10-17 1998-10-16 Vaccins veterinaires

Country Status (5)

Country Link
EP (1) EP1023083A4 (fr)
AU (1) AU753804B2 (fr)
CA (1) CA2307000C (fr)
NZ (1) NZ503636A (fr)
WO (1) WO1999020305A1 (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2824279B1 (fr) * 2001-05-04 2004-05-28 Seppic Sa Emulsion e/h concentree
FR2824269B1 (fr) * 2001-09-03 2012-03-02 Seppic Sa Composition adjuvante constituee de 1% a 15% de tensioactifs a hlb global compris entre 5 et 8 et de 85% a 99% de corps gras
NZ569627A (en) 2005-12-15 2012-01-12 Hancroft Pty Ltd The use of virginiamycin for preventing reduced feed intake and treating laminitis, fermentative acidosis, equine grass sickness and pulpy kidney
FR2903602B1 (fr) * 2006-07-12 2012-10-26 Seppic Sa Formulation injectable a liberation prolongee de principes actifs, procede pour sa preparation
FR2922767B1 (fr) 2007-10-24 2009-12-18 Seppic Sa Procede de preparation d'une composition vaccinale comprenant au moins un antigene et au moins un adjuvant.
CN106177935A (zh) * 2016-08-19 2016-12-07 齐鲁动物保健品有限公司 一种反刍动物梭菌病四联灭活疫苗及其制备方法
GB201718251D0 (en) * 2017-11-03 2017-12-20 Univ Sydney Vaccine Compositions

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1128325A (en) * 1964-11-11 1968-09-25 Wellcome Found Improvements in water-in-oil emulsion vaccines
US5424067A (en) * 1989-07-03 1995-06-13 Societe D'exploitation De Produits Pour Les Industries Chimiques (S.E.P.P.I.C.) Injectable multi-phase emulsions

Family Cites Families (4)

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Publication number Priority date Publication date Assignee Title
US3843451A (en) * 1970-08-20 1974-10-22 Burroughs Wellcome Co Microorganism production
FR2717694B1 (fr) * 1994-03-22 1996-05-03 Seppic Sa Une composition comprenant un plasmide recombinant et ses utilisations comme vaccin et médicament.
DE69636889T2 (de) * 1995-11-30 2007-12-06 Nof Corp. Öladjuvierter Impfstoff und Verfahren zu seiner Herstellung
GB9626865D0 (en) * 1996-12-24 1997-02-12 Cyanamid Websters Pty Limited Veterinary vaccines

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1128325A (en) * 1964-11-11 1968-09-25 Wellcome Found Improvements in water-in-oil emulsion vaccines
US5424067A (en) * 1989-07-03 1995-06-13 Societe D'exploitation De Produits Pour Les Industries Chimiques (S.E.P.P.I.C.) Injectable multi-phase emulsions

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
D.E.S. STEWART-HULL ET AL.: "Immunosuppressive effect in mycobacterial adjuvant emulsions of mineral oils containing low molecular weight hydrocarbons" INTERNATIONAL ARCHIVES OF ALLERGY AND APPLIED IMMUNOLOGY, vol. 52, no. 1-4, 1976, pages 118-128, XP008063925 CHBASEL *
See also references of WO9920305A1 *

Also Published As

Publication number Publication date
AU9616198A (en) 1999-05-10
AU753804B2 (en) 2002-10-31
EP1023083A4 (fr) 2006-06-14
WO1999020305A8 (fr) 1999-07-08
NZ503636A (en) 2002-05-31
CA2307000A1 (fr) 1999-04-29
CA2307000C (fr) 2011-01-04
WO1999020305A1 (fr) 1999-04-29

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