WO2009080767A1 - Fish vaccine - Google Patents
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- WO2009080767A1 WO2009080767A1 PCT/EP2008/068063 EP2008068063W WO2009080767A1 WO 2009080767 A1 WO2009080767 A1 WO 2009080767A1 EP 2008068063 W EP2008068063 W EP 2008068063W WO 2009080767 A1 WO2009080767 A1 WO 2009080767A1
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- nocardia
- fish
- virus
- fτee
- vaccine
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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
- A61K39/02—Bacterial antigens
- A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
-
- 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
- A61K39/05—Actinobacteria, e.g. Actinomyces, Streptomyces, Nocardia, Bifidobacterium, Gardnerella, Corynebacterium; Propionibacterium
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/102—Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/107—Vibrio
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K2035/11—Medicinal preparations comprising living procariotic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/521—Bacterial cells; Fungal cells; Protozoal cells inactivated (killed)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/522—Bacterial cells; Fungal cells; Protozoal cells avirulent or attenuated
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
-
- 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
- A61K2039/70—Multivalent vaccine
Definitions
- the present invention relates to a Nocardia-f ⁇ ee combination vaccine for combating bacterial infection in fish, to the use of bacteria for the manufacture of such a vaccine, to methods for the preparation of such a vaccine and to a kit-of-parts.
- Bacteria found to be pathogenic to fish belong i.a. to the genus Nocardia, Vibrio, Pasteurella, Photobacterium, Tenacibaculum, Flavobacterium, Flexibacter, Cytophaga, Francisella, Mycobacterium, Streptococcus, Lactococcus or Edwardsiella.
- Nocardia seriolae causes chronic problems in warm- water fish.
- the damage caused in fish farming industry by Nocardial infection has been increasing over the years.
- yellowtail ⁇ Seriolae quinqueradiata amberjack ⁇ Seriolae dumerell ⁇
- sea bass ⁇ Lateolabrax japonicus
- yellow croacker ⁇ Lamitichthys crocea
- Pomfret Pampus argenteus
- Threadfin ⁇ Eleutheronema tetradactylum
- Snapper Litjanus sp
- the disease often referred to as marine nocardiosis begins as a silent infection. It develops in fry and juvenile fish. The bacteria multiply within major organs such as spleen, liver and kidney.
- the bacterium can multiply in fish tissue for a long time before any visual symptoms arise. Therefore, the disease is called chronic. Economic losses are significant, if only for the fact that as a consequence fish weigh often between 300 and 1000 g when the outbreak becomes manifest.
- Nocardia seems to be a very poor inducer of the immune system itself, because in spite of the very slow progress of the disease, the immune system does not manage to clear the infection. This may also explain the fact that no efficacious vaccines against Nocardia infection exist. Vaccines comprising live attenuated or inactivated bacteria to a certain extent mimic the natural infection, but if even the natural infection fails to induce an adequate immune response, one would not expect vaccines to perform better.
- Nocardia-f ⁇ ee combination vaccine comprising bacteria of the species Lactococcus garviae, Pasteurella piscicida (also known as Photobacterium damselae subspecies piscicidae) and Vibrio anguillarum (currently also known as Listonella anguillarum) , not only provides protection against Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum infection as expected, but also and fully unexpectedly provides a significant level of protection against Nocardia seriolae infection. Most surprisingly, this level of protection against Nocardia seriolae infection is significantly higher than that obtained by a monovalent Nocardia seriolae vaccine.
- a first embodiment of the present invention relates to a Nocardia-f ⁇ ee combination vaccine for combating Nocardia infection in fish, characterised in that said vaccine comprises bacteria of the species Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum and a pharmaceutically acceptable carrier.
- said vaccine comprises bacteria of the species Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum and a pharmaceutically acceptable carrier.
- the working mechanism behind this unexpected finding is currently unknown. It is assumed however that a component present on or attached to the cell surface of the bacteria used, is a powerful stimulator of cross-specific immunity in fish against Nocardia. Cross-specific in this respect means: not induced by Nocardia but nevertheless providing protection against Nocardia.
- inactivation is not very relevant for the activity of the bacteria.
- Classical methods for inactivation such as UV-radiation, gamma- radiation, treatment with formalin, binary ethylene-imine, thimerosal and the like, all well-known in the art, are applicable.
- Inactivation of bacteria by means of physical stress using e.g. a French Press provides an equally suitable starting material for the manufacturing of a vaccine according to the invention.
- Inactivated bacteria need thus not necessarily be in the form of inactivated whole cells; the cells may be disrupted.
- Inactivated bacteria have the advantage over live attenuated bacteria that they are very safe.
- the invention relates to a combination vaccine according to the invention wherein the bacterial species are inactivated
- Live attenuated bacteria are also very suitable, because they by definition carry the factor stimulating the cross-specific immunity against Nocardia. And live attenuated bacteria have the advantage over inactivated bacteria that, especially when given without an adjuvant, they are more effective than inactivated bacteria. Moreover they replicate to a certain extent until they are stopped by the immune system, as a result of which a lower number of cells can be given.
- a live attenuated bacterium is a bacterium that is less pathogenic than its wild-type counterpart, but nevertheless induces an efficacious immune response. Attenuated strains can be obtained along classical routes, long known in the art such as serial passage, temperature-adaptation, chemical mutagenesis, UV-radiation and the like, or by site- directed mutagenesis.
- the invention relates to a combination vaccine according to the invention wherein at least one of the bacterial species is in a live attenuated form.
- Vaccines according to the invention can be prepared starting from a bacterial culture according to techniques well known to the skilled practitioner.
- Vaccines according to the invention basically comprise an effective amount of bacteria according to the invention and a pharmaceutically acceptable carrier.
- the term "effective" as used herein is defined as the amount sufficient to induce an immune response in the target fish that results in a level of pathogenesis that is less that 50% of the pathogenesis seen in non-vaccinated fish under the same conditions, and infected with wild-type Nocardia.
- the amount of cells to be administered will depend i.a. on the amount of bacteria of each species used, the condition of the bacteria; attenuated live or inactivated, the presence of an adjuvant and the route of administration.
- vaccines according to the invention can be prepared starting from a bacterial culture according to techniques well known to the skilled practitioner. In the Example-section, examples of the preparation of a vaccine according to the invention are given.
- vaccines manufactured according to the invention that are based upon inactivated bacteria can be given in general in a dosage of 10 3 to 10 10 , preferably 10 6 to 10 9 , more preferably between 10 8 and 10 9 bacteria.
- a dose exceeding 10 10 bacteria, although immunologically suitable, will be less attractive for economical reasons.
- Vaccines manufactured according to the invention that are based upon live attenuated bacteria can be given in a lower dose, due to the fact that the bacteria will continue replicating for a certain time after administration.
- Vaccines manufactured according to the invention that are based upon live attenuated bacteria can be given in general in a dosage of 10 2 to 10 8 , preferably 10 3 to 10 5 bacteria
- a vaccine according to the invention examples include sterile water, saline, aqueous buffers such as PBS and the like.
- a vaccine according to the invention may comprise other additives such as adjuvants, stabilisers, anti-oxidants and others, as described below.
- Vaccines manufactured as described in the present invention may in a preferred presentation contain an immunostimulatory substance, a so-called adjuvant.
- Adjuvants in general comprise substances that boost the immune response of the host in a non-specific manner.
- a number of different adjuvants are known in the art. Examples of adjuvants frequently used in fish and shellfish farming are muramyldipeptides, lipopolysaccharides, several glucans and glycans and Carbopol(R).
- An extensive overview of adjuvants suitable for fish and shellfish vaccines is given in the review paper by Jan Raa (Reviews in Fisheries Science 4(3): 229-288 (1996)).
- the vaccine may also comprise a so-called "vehicle".
- a vehicle is a compound to which the bacterium adheres, without being covalently bound to it. Such vehicles are i.a. bio-microcapsules, micro-alginates, liposomes and macrosols, all known in the art.
- a special form of such a vehicle, in which the antigen is partially embedded in the vehicle, is the so-called ISCOM (European Patents EP 109.942, EP 180.564, EP 242.380).
- the vaccine may comprise one or more suitable surface-active compounds or emulsifiers, e.g. Span or Tween.
- suitable surface-active compounds or emulsifiers e.g. Span or Tween.
- the combination vaccine according to the invention comprises an adjuvant.
- oil adjuvants usually turn out to be somewhat more efficient.
- Oil adjuvants suitable for use in water-in-oil emulsions are e.g. mineral oils or metabolisable oils.
- Mineral oils are e.g. Bayol ® , Marcol ® and Drakeol ® .
- Metabolisable oils are e.g. vegetable oils, such as peanut oil and soybean oil, animal oils such as the fish oils squalane and squalene, and tocopherol and its derivatives.
- Suitable adjuvants are e.g. w/o emulsions, o/w emulsions and w/o/w double-emulsions
- Very suitable o/w emulsions are e.g. obtained starting from 5-50% w/w water phase and 95-50% w/w oil adjuvant, more preferably 20-50% w/w water phase and 80-50% w/w oil adjuvant.
- the combination vaccine according to the invention comprises an adjuvant, wherein that adjuvant is an oil adjuvant.
- oil adjuvants can roughly be divided in adjuvants comprising mineral oil and adjuvants comprising non-mineral oil.
- Mineral oil may be somewhat less attractive, both from a food safety point of view and due to the lesions it sometimes gives. Therefore, a preferred oil adjuvant comprises a non-mineral oil.
- a more preferred non-mineral oil is e.g. ISA 763A VG oil as commercially obtainable from SEPPIC France
- the amount of adjuvant added depends on the nature of the adjuvant itself, and information with respect to such amounts will be provided by the manufacturer.
- the vaccine is mixed with stabilisers, e.g. to protect degradation-prone proteins from being degraded, to enhance the shelf- life of the vaccine, or to improve freeze-drying efficiency.
- Useful stabilisers are i.a. SPGA (Bovarnik et al; J. Bacteriology 59: 509 (1950)), carbohydrates e.g. sorbitol, mannitol, trehalose, starch, sucrose, dextran or glucose, proteins such as albumin or casein or degradation products thereof, and buffers, such as alkali metal phosphates.
- vaccines as described are presented in a freeze-dried form.
- the vaccine may be suspended in a physiologically acceptable diluent.
- the vaccines as described are preferably administered to the fish via injection such as e.g. intraperitoneal injection, immersion, spraying, dipping or per oral. It should be kept in mind however that the route of administration may also depend on the type of vaccine: if the vaccine comprises live attenuated Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum bacteria, it could easily be administered by dipping.
- the vaccine comprises Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum bacteria in the form of inactivated bacteria, or more generally spoken if the vaccine can be improved by admixing an adjuvant, the preferred way of administration would be the intraperitoneal route.
- intraperitoneal vaccination is an effective route of vaccination in fish, certainly for inactivated bacteria, especially because it allows the incorporation of adjuvants.
- a convenient way of making a vaccine according to the invention is, to make use of commercially available vaccines. Lactococcus garviae vaccines, Pasteurella piscicida vaccines and Vibrio anguillarum vaccines are commercially available, and/or ways to produce them have been described in the literature.
- the administration protocol can be optimized in accordance with standard vaccination practice.
- the age of the fish to be vaccinated is not critical, although clearly one would want to vaccinate against Nocardia infection in an early stage.
- the vaccine is preferably mixed with a suitable carrier for oral administration i.e. cellulose, food or a metabolisable substance such as alpha-cellulose or various oils of vegetable or animals origin.
- a suitable carrier for oral administration i.e. cellulose, food or a metabolisable substance such as alpha-cellulose or various oils of vegetable or animals origin.
- an attractive method is administration of the vaccine through bio encapsulation whereby live feed is exposed to high concentrations of the vaccine, followed by the feeding of the live- feed organisms to the fish.
- Particularly preferred food carriers for oral delivery of the vaccine according to the invention are live-feed organisms which are able to encapsulate the vaccine.
- Suitable live-feed organisms include plankton-like non-selective filter feeders preferably members of Rotifera, Artemia, and the like. Highly preferred is the brine shrimp Artemia sp..
- the Nocardia-f ⁇ ee combination vaccine according to the invention comprises, in addition to bacteria of the species Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum, at least one other microorganism or virus that is pathogenic to fish, or one other antigen of such a microorganism or virus or genetic material encoding said other antigen.
- At least one other microorganism that is pathogenic to fish, or one other antigen of such a microorganism or genetic material encoding said other antigen are selected from the group of bacteria consisting of the bacterium causing Big Belly syndrome, Flavobacterium columnare, Tenacibaculum maritimum, Streptococcus iniae, Streptococcus difficile, Streptococcus agalactiae, Streptococcus dysgalactiae, Edwardsiella tarda, Edwardsiella ictaluri, Mycobacterium maritimum, Francisella sp., Nodavirus, Irido virus, Koi herpes virus, Channel Catfish virus.
- Still another embodiment of the present invention relates to methods for the production of vaccines for combating Nocardia infection in fish.
- Such methods comprise the step of mixing of Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum bacteria in a live attenuated or inactivated form and a pharmaceutically acceptable carrier.
- a preferred form of this embodiment relates to methods that additionally comprise the mixing of an adjuvant.
- Lactococcus garviae Pasteurella piscicida and Vibrio anguillarum vaccine components, ready-to-use vaccines are used, they can be mixed before administration.
- the vaccine is administered by injection, for simultaneous administration the components can be mixed, they can also be administered separately or sequentially in a series of consecutive injections.
- the skilled person would prefer to use that amount of each of the bacteria that is necessary to induce an immune response against each of the bacterial species.
- the amount of Lactococcus garviae bacteria in the Nocardia-f ⁇ ee vaccine according to the invention preferably is sufficient to induce an immune response against Lactococcus garviae infection.
- the bacteria of the species Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum in the combination vaccine can be administered simultaneously, separately or sequentially.
- Simultaneous administration is administration of the Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum bacteria at the same moment in time, preferably injected as a mixture. This would of course be the preferred method of administration, due to ease of handling.
- Separate administration is administration of the Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum bacteria (partially or fully) separately at two or more different injection sites, preferably at the same moment in time.
- Sequential administration is administration during which the Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum bacteria are administered at different moments in time. It is clear that if separate or sequential injections are given, these would preferably be given at the same day, more preferably within 12, 10, 8, 6, 4, 2 or 1 hour in that order of preference. Even more preferred is administration within 50, 40, 30, 20, 10 or 5 minutes after each other. If the administration of all vaccines of the combination vaccine would take place within 10 minutes, even better 5 or less than 5 minutes, a single moment for handling of each fish would suffice, and would allow an almost instantaneous start of triggering of the immune system.
- Another embodiment of the present invention relates to the use of bacteria of at least the species Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum for the manufacture of a Nocardia-f ⁇ ee combination vaccine for combating Nocardia seriolae infection in fish.
- the fish in which the Nocardia seriolae infection is to be combated, and for which the vaccine is thus manufactured belongs to the species yellowtail
- At least one of the bacterial species used for the manufacture is in a live attenuated form. In still another preferred form of this embodiment, the bacterial species used for the manufacture are inactivated.
- said vaccine additionally at least one other microorganism or virus that is pathogenic to fish, or one other antigen of such a microorganism or virus or genetic material encoding said other antigen is used.
- said other microorganism or virus is selected from the group of bacteria consisting of the bacterium causing Big Belly syndrome, Tenacibaculum maritimum, Flavobacterium columnare, Streptococcus iniae, Streptococcus difficile, Streptococcus agalactiae, Streptococcus dysgalactiae, Edwardsiella tarda, Edwardsiella ictaluri, Mycobacterium maritimum, Francisella sp., Nodavirus, Irido virus, Koi herpes virus and Channel Catfish virus.
- kits of parts wherein the kit comprises at least two vaccine vials, and these at least two vials together comprise bacteria of the species Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum and a pharmaceutically acceptable carrier for combating Nocardia seriolae infection in fish.
- the kit comprises two vials together comprising bacteria of the species Lactococcus garviae, Pasteurella piscicida and Vibrio anguillarum, this means that each of these three types of bacteria are present in at least one of the vials. As a result the three types of bacteria are all present in the kit.
- one vial could comprise Lactococcus garviae, whereas the other vial comprises Pasteurella piscicida and Vibrio anguillarum.
- one vial could comprise Lactococcus garviae and Pasteurella piscicida, whereas the other vial could comprise Vibrio anguillarum.
- the kit comprises e.g. three vials, each type of bacteria can be present in one vial.
- feed was given ad libitum several times per day. As soon as a sufficient number of fish reached the desired weight of approximately 20 g and were shown to be free of infections they were transferred to experimental tanks. During the experimental period (after vaccination) the fish were fed at 2-3% of their body weight (BW) (adjusted weekly). The amount of feed per Kg body weight was kept as similar as possible for vaccinated and mock-vaccinated fish. At weekly intervals, 10-15 fish per group were weighed in groups to determine the mean fish weight for the recalculation of the feed amount. Fish were starved for 24 hours prior to the vaccination to ensure complete emptying of the gastro-intestinal tract and thereby preventing injury to the internal organs as a result of the injection. After challenge fish were fed 1-3% BW.
- the fish were grouped, vaccinated or mock-vaccinated and subsequently transferred to 500 L tanks.
- Groups of fish were separated by means of a net placed vertically in the middle of the tank, dividing the tank in two halves. Tank halves were identified by the tank number and a letter (A or B). After challenge fish were housed in 50 L tanks.
- This suspension representing a late log phase was used to prepare the challenge suspension.
- An appropriate dilution was performed in saline and used for injection.
- the results of the challenges performed for each of the vaccine formulations was evaluated by calculating the Relative Percentage Survival (RPS) values for each group as compared to the control group the day that control mortality reached 60% or more.
- RPS Relative Percentage Survival
- statistical analysis was performed on final confirmed cumulative mortality between treatment groups and respective controls using a 2x2 contingency table and Fisher's exact test (One tailed, Stat Soft Inc (2004), Statistica, data analysis Software system, version 6).
- the RPS values are calculated according to the following formula:
- RPS ⁇ 1 - ( ) x 100
- the antigen concentration in the Examples will often be given in ODU/ml.
- AU monovalent vaccines described here were derived from a formalin inactivated N. seriolae antigens and formulated as oil adjuvanted vaccines.
- the vaccines Vl and V2 were injected using an injection volume of 0.05.
- the vaccines V3, V4 and V5 were injected after mixing equal volumes of vaccine with vaccine diluent and injection of 0. ImI.
- Vaccine 1 Type: Monovalent N. seriolae /oil adjuvanted
- Vaccine 2 Type: Monovalent N. seriolae I oil adjuvanted
- Vaccine 3 Type: Monovalent N. seriolae /oil adjuvanted
- Vaccine 5 Type: Monovalent N. seriolae I oil adjuvanted
- SVDB Standard vaccine dilution buffer
- the vaccine formulations tested are listed in Table 1.
- the vaccines are water in oil vaccines formulated as a micro component and mixed with ISA 763A VG oil- vaccine diluent before use.
- the vaccine formulations tested are listed in Table 3.
- the vaccine was a water in oil vaccine formulated as a micro component and was mixed with ISA 763A VG oil- vaccine diluent before use.
- the antigen used for these vaccines are derived from the normal production strains of P. piscicida, L. garvieae and V anguillarum.
- Table 3 Experimental groups, vaccines used, allocated tank halves after vaccination and challenge.
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Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
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JP2010538768A JP2011506577A (en) | 2007-12-21 | 2008-12-19 | Fish vaccine |
CN2008801218637A CN101903042A (en) | 2007-12-21 | 2008-12-19 | Fish vaccine |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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EP07150349 | 2007-12-21 | ||
EP07150349.4 | 2007-12-21 |
Publications (1)
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WO2009080767A1 true WO2009080767A1 (en) | 2009-07-02 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/EP2008/068063 WO2009080767A1 (en) | 2007-12-21 | 2008-12-19 | Fish vaccine |
Country Status (5)
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JP (1) | JP2011506577A (en) |
KR (1) | KR20100108373A (en) |
CN (1) | CN101903042A (en) |
TW (1) | TW200936759A (en) |
WO (1) | WO2009080767A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011073990A (en) * | 2009-09-29 | 2011-04-14 | Meiji Seika Kaisha Ltd | Dna vaccine and bcg vaccine against nocardiosis in marine fish |
CN109865136A (en) * | 2019-03-18 | 2019-06-11 | 宁波大学 | A kind of silvery pomfret bivalent inactivated vaccine |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN104232535B (en) * | 2014-09-02 | 2017-04-26 | 广东海洋大学 | Nocardia seriolae induced low virulent strain and application thereof |
KR101723466B1 (en) * | 2015-10-08 | 2017-04-06 | 주식회사 인트론바이오테크놀로지 | Novel Streptococcus iniae bacteriophage Str-INP-1 and its use for preventing proliferation of Streptococcus iniae |
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WO2005053716A1 (en) * | 2003-12-03 | 2005-06-16 | Akzo Nobel N.V. | Streptococcus phocae vaccine |
WO2007031572A1 (en) * | 2005-09-16 | 2007-03-22 | Intervet International B.V. | Fish vaccine |
WO2007138036A1 (en) * | 2006-05-30 | 2007-12-06 | Intervet International B.V. | Vaccine against rickettsia-like organisms |
JP2007326794A (en) * | 2006-06-06 | 2007-12-20 | Kyoritsu Seiyaku Kk | Inactivated vaccine using fish streptococcus dysgalactiae as antigen |
WO2008074783A1 (en) * | 2006-12-18 | 2008-06-26 | Intervet International B.V. | Immune stimulant against fish pathogenic bacteria |
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2008
- 2008-12-01 TW TW097146647A patent/TW200936759A/en unknown
- 2008-12-19 CN CN2008801218637A patent/CN101903042A/en active Pending
- 2008-12-19 KR KR1020107015065A patent/KR20100108373A/en not_active Application Discontinuation
- 2008-12-19 JP JP2010538768A patent/JP2011506577A/en not_active Withdrawn
- 2008-12-19 WO PCT/EP2008/068063 patent/WO2009080767A1/en active Application Filing
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CN109865136A (en) * | 2019-03-18 | 2019-06-11 | 宁波大学 | A kind of silvery pomfret bivalent inactivated vaccine |
Also Published As
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CN101903042A (en) | 2010-12-01 |
KR20100108373A (en) | 2010-10-06 |
TW200936759A (en) | 2009-09-01 |
JP2011506577A (en) | 2011-03-03 |
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