AU2002255851A1 - Microbial feeds for aquaculture and agriculture - Google Patents
Microbial feeds for aquaculture and agricultureInfo
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- AU2002255851A1 AU2002255851A1 AU2002255851A AU2002255851A AU2002255851A1 AU 2002255851 A1 AU2002255851 A1 AU 2002255851A1 AU 2002255851 A AU2002255851 A AU 2002255851A AU 2002255851 A AU2002255851 A AU 2002255851A AU 2002255851 A1 AU2002255851 A1 AU 2002255851A1
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- proteins
- therapeutic
- protein
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Description
Delivery Of Disease Control In Aquaculture and Agriculture
Using Microbes Containing Bioactive Proteins
BACKGROUND OF THE INVENTION
Field of the Invention
[001] This invention is directed to the use of microbial cells which are used as feed components in aquaculture or agriculture, and which also contain exogenous peptides, proteins, and/or antibodies, which will convey resistance or immunity to viral or bacterial pathogens or otherwise improve the health and performance of the species consuming said microbial cells. The microbial cells can be yeast, fungi, bacteria, or algae. The proteins and/or antibodies may be expressed inside the microbial cells by direct genetic modification of the microbe itself, or by the infection of the microbe with a virus that has been altered to express the protein of interest.
Related Art
[002] Certain plant products have been produced using specific genetic modification to express proteins and/or antibodies of therapeutic value. The group at the Boyce Thompson Institute at Cornell has been cloning viral coat protein into bananas and potatoes so that when ingested, this will be equivalent to delivering an oral vaccine. This concept has not been extended to microbes.
[003] There are several plant biotech companies such as Meristem, Large Scale Biology, and Prodigene, which are now expressing certain human therapeutic proteins in the plants including antibodies.
[004] Recombinant microbes including bacteria, yeast and fungi have been used to produce human therapeutic proteins. However, such recombinant microbes have not been used for agricultural purposes incorporating ingestion of the whole organism. In both the plant and microbial cases, the recombinant organism has simply been used as a factory, and the therapeutic protein is then isolated and purified prior to use.
[005] Certain plant products have been produced which contain proteins and/or antibodies of therapeutic value by infecting the plant with a virus that expresses the protein of interest. Large Scale Biology has a series of patents protecting this technology but these patents do not disclose the use of the technology in microbes and certainly not algae.
[006] Antibiotic doping is used routinely in the aquaculture setting. Typically, the pure or semipure antibiotics are added directly to the water column; however, crude fermentation broths, or crude preparations including cells, have not been used for any kind of therapeutic delivery system.
[007] Production of amino acids such as lysine typically involves a genetically modified microorganism, which overproduces the amino acid of interest and excretes it into the fermentation medium. The wastestream from such a fermentation would include biomass containing the amino acid, and this wastestream product could be used as a crude delivery form of the small molecule nutritive amino acid.
SUMMARY OF THE INVENTION
[008] The present invention provides for a composition of matter (the feed) and the use of this feed for the delivery of a therapeutic dose of a bioactive peptide or protein.
[009] In one embodiment, this invention provides an aquaculture feed containing microbial biomass comprising one or more proteins, antibodies, or a combination thereof, where the proteins and antibodies are non-native to the microbes of the biomass. Preferably, the microbes are selected from yeast, fungi, bacteria, algae, or combinations thereof. The microbes may be engineered to recombinantly express the proteins or antibodies recombinantly, or the microbes may be infected with viruses or plasmids, which express the recombinant proteins or antibodies.
[010] In another embodiment, this invention provides a method of delivering therapeutic proteins to an animal comprising administering to an animal a feed comprising a microbe expressing a non-native therapeutic protein. This method is particularly suitable for the non-human animal subjected to intensive agricultural practices, or for fish or shellfish in aquaculture. Preferred microbes are algae. In a preferred mode, the therapeutic protein is a recombinant protein expressed by the microbe or the microbe is infected by a recombinant virus, which expresses the recombinant therapeutic or bioactive protein. Preferred therapeutic proteins include a protein which inhibits growth or replication of Vibrio species in vitro, or a
protein which inhibits Taura Syndrome Virus (TSV) or White Spot Syndrome Virus (WSSV) infection in shrimp, or a recombinantly expressed antibody.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[011] Microalgae (single cell alga, or phytoplankton) represent the largest, but most poorly understood, kingdom of microorganisms on the earth. Like plants are to terrestrial animals, the microalgae represent the natural nutritional base and primary source of all the phytonutrients in the aquatic food chain. As the primary link in the aquatic food chain, microalgae are the source of many more phytonutrients than simply DHA and ARA. Microalgae also represent a vast genetic resource comprising in excess of 80,000 different species. Yeast, fungi and bacteria are also in the direct food chain of fish, crustaceans and mollusks. However, only a very few of these microbes, perhaps less than 10 species, have been exploited for aquaculture feeds. These few species have been used primarily for historical reasons and ease of cultivation. They have not been chosen on the basis of any scientific evidence of superiority as nutritional or therapeutic supplements.
[012] The marine environment is filled with bacteria and viruses that can attack fish and shellfish thereby devastating intensive farms very quickly. Bacteria and viruses can also attack single celled microalgae, so these organisms have evolved biochemical mechanisms to defend themselves from such attacks. Such mechanisms may involve the secretion of compounds that inhibit bacterial growth or viral attachment. Such compounds are called
"prebiotics" and have effects similar to how cranberry juice can prevent bladder infections in humans. When nutritional, therapeutic or protective effects are delivered via the whole live organisms, such as Lactobacillis in yogurt, such products are referred to as "probiotics" and the organisms are "probionts". For the purposes of this invention, both types of action will be referred to as probiotic.
[013] Several algal species exhibit antibiotic activity. This activity may be due to certain bioactive constituents in the membranes or cell walls, the protein or the carbohydrate of the positively testing species that inhibit bacterial growth (prebiotics or herein probiotics). Any standard screening technique used to identify antibiotic agents may be used to screen for algae having antibiotic activity, including incubating filter disks soaked in culture broth from the candidate algae on a lawn of the target pathogenic microbe (e.g., Vibrio species). This invention contemplates the use of these "friendly algae" in a probiotic fashion to control the growth of certain "pathogenic microorganisms" in a pond. However, the main aspect of this invention is directed to the use of recombinant microbes or virus infected microbes to deliver the bioactive protein of choice. The recombinant microbes or virus-infected microbes may be tested for antibiotic activity by standard antibiotic screening assays to confirm their activity.
[014] Historically, only bacteria have been used in a probiotic fashion to alter a pond's ecology in order to eliminate or reduce the number of pathogenic bacteria. A problem with the bacterial probiotic approach is that
the existing microbial ecology represents a massive buffer that is difficult to modulate with the introduction of relatively small numbers of alternative bacteria and the results to date have been unimpressive. Furthermore, even if the newly introduced bacteria do bloom, any large increase in bacterial levels in a pond can lower oxygen levels and cause harm to the fish or shrimp. The use of photosynthetic microalgae overcomes this problem as they actually increase oxygen levels. Microalgae have not been considered before as probiotics. Previous experience in the screening of extensive algal culture collections has indicated a number of algal species that exhibit antibacterial or bacteriostatic capabilities. Some of these activities may be anti-Vibrio activity. Such species would be candidates for a high value enrichment feed that delivers both nutritional and antibiotic capabilities. This invention provides an approach to disease control which may be the solution to an impending ecological disaster that will result from the present uncontrolled practice of dumping of toxic chemicals and antibiotics into the water systems to control these bacterial, fungal or viral pathogens.
[015] One of the major disease control problems in shrimp aquaculture today is infection by certain viruses (e.g., White Spot Syndrome Virus and Tara Syndrome Virus). Neither current antibiotic, nor probiotic strategies will work in this situation, and shrimp cannot be vaccinated in a way similar to fish. Shrimp have only a rudimentary immune system so they are particularly susceptible to devastation by viral attacks. This invention provides a solution to this problem using a biological control method using microalgae
as the vector to deliver anti-White Spot antibodies directly to the shrimp. These "Designer feeds" would be a normal part of the diet, but modified to deliver a therapeutic dose of antibody directly to the gut of the shrimp. This approach is known as "passive immunity" because the antibody remains outside the host organism and simply prevents infestation through the gut wall. The invention envisions the use of transgenic algae, yeast, fungi or bacteria to deliver the antibody to the virus. Such probiotics, as envisioned in the invention, do not have to replicate in the target organism for the desired effect to occur. Alternatively, the microbe itself may be infected with a virus that is engineered to produce the antibody of interest. Alternatively, the microbial source may deliver a portion of the virus (e.g. a coat protein or coat proteins) or fragment thereof in order to immunize the shrimp, other shellfish, finfish or other animals.
[016] Antibodies to desired targets, such as White Spot Syndrome Virus or Taura Syndrome Virus, may be prepared by routine immunization and selection of monoclonal antibody producing hybridomas, or by screening viral or bacterial expression libraries of immunoglobulin genes and gene fragments. See "Current Protocols in Immunology," Coligan, et al., eds, Wiley Interscience, 1991 , and periodic supplements. Nucleic acid sequences encoding the binding sites of the selected antibodies can be cloned using standard methods (see "Current Protocols in Molecular Biology." Ausubel, et al., eds., Wiley-lnterscience, 1987, and periodic supplements), and antibodies may be expressed from recombinant microbes (including algae, see, e.g.,
U.S. Patent No. 6,027,900) or cloned into viruses that infect the desired microbes.
[017] There are a number of bactericidal and bacteriostatic peptides, which will inhibit microbial growth and that include, but are not limited to cecropins, penaeidins, bactenecins, callinectins, myticins, tachyplesins, clavanins, misgurins, pleurocidins, parasins, histones, acidic proteins, and lysozymes. These peptides may be expressed in a microbial biomass such as algae, yeast, fungi or bacteria using recombinant methods as described above, and thus provided as a feed component to convey resistance to infestation.
[018] The invention as contemplated herein, is described in the following examples, but its utility is not limited to the examples provided.
EXAMPLES [019] Example 1. Selection of Useful Microbial Sources for Feeds
that Provide Disease Control. Microalgal biomass samples, aqueous extracts, organic extracts and extracts from the growth medium after cultivation of the algae were concentrated and spotted on filter paper discs.
Using sterile techniques, these discs were then placed on agar plates overlaid with a lawn of selected organisms including but not limited to gram-negative bacteria, gram-positive bacteria, antibiotic resistant bacteria, yeast, or fungi.
After incubation for an appropriate length of time to allow growth of the lawn of test organism the samples were plates were observed for zones of clearing
(non-growth) around the filter paper discs. Large zones of clearing indicate
potent antibiotic activity; small zones of clearing indicate less potent antibiotic activity.
[020] Example 2. Incorporation of an antibody into an algal feed.
A particular viral or bacterial pathogen is chosen and used to prepare monoclonal antibodies using procedures well known to experts in this field. Gene(s) coding for this antibody or an appropriate antibody fragment (Fab or Fv) are isolated and amplified in the appropriate vector. The gene is spliced into a transformation vector suitable for a eukaryotic algae or a prokaryotic alga (e.g. Synechocystis), or a yeast (e.g. Saccharomyces) or a fungus (e.g. Mortierella). The transformation vector is chosen so that the antibody will be over expressed in the microbial cell biomass. This biomass is then used as a feed additive in such a way as to provide the antibody directly to the animal thus providing passive immunity.
[021] Example 3. Expression of a bactericidal protein in a
microbial feed. A bactericidal protein is chosen for the particular application. For example, proteins of the penaeidin class may be chosen for pathogenic control in shrimp. Penaeidins are members of a family of antimicrobial peptides isolated from crustaceans (e.g., Penaeid shrimp). Antimicrobial peptides may also come from insects and chelicerates and may include but are not limited to cecropins, peneaidins, bactenecins, callinectins, myticins, tachyplesins, clavanins, misgunins, pleurocidins, parasins, histones, acidic proteins, and lysozymes. The gene for the chosen protein or peptide is either isolated from the original source, an amplification source, or it can be made
synthetically. The gene is then incorporated into a transformation vector suitable for a eukaryotic algae (e.g. Chlorella) or a prokaryotic alga (e.g. Synechocystis), or a yeast (e.g. Saccharomyces) or a fungus (e.g. Mortierella). The transformation vector is chosen so that the protein will be over expressed in the microbial cell biomass. This biomass is then used as a feed additive in such a way as to provide the bactericidal protein directly to the animal thus providing resistance to that particular pathogen.
[022] Example 4. Vaccination using Feeds. An antigen characteristic to a particular pathogen is chosen as is required by the animal and circumstances. For example, a viral coat protein(s) or component thereof, or an infectious bacterial protein, or a component thereof is chosen. The gene coding for the protein(s) is isolated and incorporated into a vector suitable for use in the microorganism of choice. The transformation vector is chosen so that the protein(s) will be over expressed in the microbial cell biomass. This biomass is then used as a feed additive in such a way as to provide the viral or bacterial or fungal protein(s) directly to the animal thus stimulating an immunological response to that particular pathogen. The microbial component may enter the body of the animal in the digestive tract, or otherwise through contact in the air or water.
[023] Example 5. Vaccination using probiotic Feeds. Probiotic bacteria such as Lactobacillus, Bacillus, Bifidobacterium, etc. provide beneficial effects by their presence as live organisms in the digestive track of an animal. As such they are constantly replicating and become a significant
portion of the intestinal microflora and make an excellent continuous delivery mechanism for oral vaccines. Oral vaccines must deliver the antigen to a portion of the intestinal mucosa where it can interact with immunogenic tissues (eg., Peyers Patches) and stimulate an immunogenic response. An antigen characteristic to a particular pathogen is chosen as is required by the animal and circumstances. For example, a viral coat protein or component thereof, or an infectious bacterial protein, or a component thereof is chosen. The gene coding for the protein is isolated and incorporated into a vector suitable for use in the probiotic microorganism of choice. Other gut microfloral components not generally considered as probiotics, but which live in the intestine, such as conforms (e.g. Escherichia coli) can also be used as a vector for producing the vaccine in situ.
[024] The two viral coat proteins from salmon infectious pancreatic necrosis virus (IPNV) are isolated and inserted into a transformation vector selected for use in Lactobacillus using molecular biology methods that are well know in the state of the art. The recombinant Lactobacillus cells expressing the viral antigens as free proteins, excreted proteins, and/or virus like particles (assembled viruses with no nucleic acid) are then grown using conventional fermentation technology, harvested and processed into a form usable as a feed for salmon. This form may include, but is not limited to freeze drying, spray drying, fluid bed drying, microencapsulation, extrusion, or tableting. The recombinant Lactobacillus is then provided to the salmon as a feed, thereby delivering both the valuable probiotic as well as the vaccine. In
this case, the vaccine is constantly produced as long as the recombinant Lactobacillus is present in the gut of the animal.
[025] Example 6. Delivery of active peptides or proteins using
probiotic feeds. The gene for an active antimicrobial peptide, such as, but not limited to, cecropins, peneaidins, bactenecins, callinectins, myticins, tachyplesins, clavanins, misgurins, pleurocidins, or parasins, or an antimicrobial protein such as histones, acidic proteins, or lysozymes is isolated and inserted into a transformation vector selected for use in Lactobacillus using molecular biology methods that are well know in the state of the art. The recombinant Lactobacillus cells expressing the free peptides or proteins, or excreted proteins, are then grown using conventional fermentation technology, harvested and processed into a form usable as a feed for an animal such as, but not limited to fish, crustaceans, livestock, etc. This form may include, but is not limited to freeze drying, spray drying, fluid bed drying, microencapsulation, extrusion, or tableting. The recombinant Lactobacillus is then provided to the animal as a feed, thereby delivering both the valuable probiotic as well as the antimicrobial compound. In this case, the antimicrobial compound is constantly produced as long as the recombinant Lactobacillus is present in the gut of the animal.
Claims (31)
1. An animal feed containing microbial biomass comprising one or more proteins, antibodies, or a combination thereof, wherein said proteins and antibodies are non-native to the microbes of the biomass.
2. The animal feed as claimed in claim 1 , wherein the microbes are selected from yeast, fungi, bacteria, algae, or combinations thereof.
3. The animal feed as claimed in claim 1 , wherein the microbes are algae.
4. The animal feed as claimed in claim 1 , wherein the microbes are yeast.
5. The animal feed as claimed in claim 1 , wherein the microbes are bacteria.
6. The animal feed as claimed in claim 1 , wherein the microbes are fungi.
7. The animal feed as claimed in claim 1 , wherein the microbes express the peptides, proteins or antibodies recombinantly.
8. The animal feed as claimed in claim 1 , wherein the microbes are infected with viruses which express the proteins or antibodies recombinantly.
9. The animal feed as claimed in claims 1-8, wherein the feed is used for aquaculture.
10. A method of delivering therapeutic, bioactive or nutritional proteins to an animal comprising administering to an animal a feed comprising a microbe expressing a non-native therapeutic, bioactive or nutritional protein.
11. The method of delivering therapeutic, bioactive or nutritional proteins as claimed in claim 10, wherein the non-human animal is subjected to intensive agricultural practices.
12. The method of delivering therapeutic, bioactive or nutritional proteins as claimed in claim 10, wherein the animal is an aquaculture species.
13. The method of delivering therapeutic, bioactive or nutritional proteins as claimed in claim 10, wherein the microbe is an alga.
14. The method of delivering therapeutic, bioactive or nutritional proteins as claimed in claim 10, wherein the microbe is a fungus.
15. The method of delivering therapeutic, bioactive or nutritional proteins as claimed in claim 10, wherein the microbe is a bacterium.
16. The method of delivering therapeutic, bioactive or nutritional proteins as claimed in claim 10, wherein the microbe is a yeast.
17. The method of delivering therapeutic, bioactive or nutritional proteins or proteins as claimed in claim 10, wherein the therapeutic protein is a recombinant protein expressed by the microbe.
18. The method of delivering therapeutic, bioactive or nutritional proteins as claimed in claim 10, wherein the microbe is infected by a recombinant virus which expresses the therapeutic protein recombinantly.
19. The method of delivering a therapeutic, bioactive or nutritional protein or proteins as claimed in claim 10, wherein the therapeutic protein is a protein which nhibits growth or replication of Vibrio species in vitro.
20. The method of delivering a therapeutic, bioactive or nutritional protein or proteins as claimed in claim 10, wherein the therapeutic protein is a protein which inhibits a virus.
21. The method of delivering a therapeutic, bioactive or nutritional protein or proteins as claimed in claim 10, wherein the therapeutic protein is a protein which inhibits Taura Syndrome or White Spot Syndrome Virus infection in shrimp.
22. The method of delivering a therapeutic, bioactive or nutritional protein or proteins as claimed in claim 10, wherein the therapeutic protein is a recombinantly expressed antibody.
23. A method as claimed in claims 10-22, wherein the therapeutic, bioactive or nutritional protein is from the following list cecropins, penaeidins, bactenecins, callinectins, myticins, tachyplesins, clavanins, misgurins, pleurocidins, parasins, histones, acidic proteins, and lysozymes.
24. A method as claimed in claims 10-22, wherein the animal is non- human.
25. A probiotic bacteria that carries a vaccine.
26. A method of delivering a vaccine to an animal comprising using a probiotic bacteria expressing that vaccine.
27. A method of delivering a vaccine to an animal comprising using a vaccine-expressing bacteria that grows in the intestine.
28. A method of immunizing an animal by providing to the animal a probiotic bacteria expressing a vaccine in the diet.
29. A probiotic bacteria, which delivers an antimicrobial compound.
30. A method of delivering an antimicrobial compound to an animal comprising using a probiotic bacteria expressing that antimicrobial compound.
31. A method of delivering an antimicrobial compound to an animal comprising using an antimicrobial-expressing bacteria that grows in the intestine.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US27794701P | 2001-03-23 | 2001-03-23 | |
US60/277,947 | 2001-03-23 | ||
PCT/US2002/008651 WO2002076391A2 (en) | 2001-03-23 | 2002-03-22 | Microbial feeds for aquaculture and agriculture |
Publications (2)
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AU2002255851A1 true AU2002255851A1 (en) | 2003-03-27 |
AU2002255851B2 AU2002255851B2 (en) | 2008-03-06 |
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AU2002255851A Ceased AU2002255851B2 (en) | 2001-03-23 | 2002-03-22 | Microbial feeds for aquaculture and agriculture |
Country Status (11)
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US (2) | US20040047881A1 (en) |
EP (4) | EP1541036A1 (en) |
JP (1) | JP2004532628A (en) |
AT (2) | ATE400189T1 (en) |
AU (1) | AU2002255851B2 (en) |
CA (1) | CA2442004A1 (en) |
DE (2) | DE60227498D1 (en) |
MX (1) | MXPA03008563A (en) |
NO (1) | NO20034244L (en) |
NZ (1) | NZ528578A (en) |
WO (1) | WO2002076391A2 (en) |
Families Citing this family (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE60227498D1 (en) | 2001-03-23 | 2008-08-21 | Advanced Bionutrition Corp | DISTRIBUTION OF AGENTS FOR THE CONTROL OF AFFECTS IN AQUACULTURE USING BIOACTIVE PROTEINS CONTAINING YEAST |
US7807144B2 (en) * | 2001-09-05 | 2010-10-05 | Academia Sinica | Oral vaccines |
WO2004025263A2 (en) * | 2002-09-16 | 2004-03-25 | Advanced Bionutrition Corporation | Protein and peptide expression for passive immunity |
AU2003294244A1 (en) * | 2002-11-07 | 2004-06-03 | Advanced Bionutrition Corp. | Nutraceuticals and method of feeding aquatic animals |
EP1578191A4 (en) * | 2002-11-14 | 2008-10-29 | Advanced Bionutrition Corp | Feed suitable for culturing rotifers, larval shrimp, and marine filter feeders |
US20070082008A1 (en) * | 2003-03-07 | 2007-04-12 | Advanced Bionutrition Corporation | Feed formulation for terrestrial and aquatic animals |
US7973148B2 (en) * | 2004-04-15 | 2011-07-05 | Advanced Bionutrition Corporation | Crustacean expression vector |
MXPA06015103A (en) * | 2004-06-17 | 2007-03-26 | Sinaloa Seafields International Inc | Managed co-cultures of organisms having prophylactic and health-promoting effects. |
KR20070026873A (en) * | 2004-06-30 | 2007-03-08 | 오메가 바이오 파마(아이.피.1) 리미티드 | Materials and methods for improving shellfish health, immunity and growth |
US20090181363A1 (en) * | 2005-12-21 | 2009-07-16 | Dhar Arun K | Non-invasive detection of fish viruses by real-time pcr |
US8968721B2 (en) | 2005-12-28 | 2015-03-03 | Advanced Bionutrition Corporation | Delivery vehicle for probiotic bacteria comprising a dry matrix of polysaccharides, saccharides and polyols in a glass form and methods of making same |
JP5214464B2 (en) | 2005-12-28 | 2013-06-19 | アドバンスド バイオニュートリション コーポレーション | Delivery medium for probiotic bacteria, in the form of glass, comprising a dry matrix of polysaccharides, saccharides and polyols and method for producing the same |
JP2009523027A (en) * | 2006-01-11 | 2009-06-18 | アテューン フーズ | Probiotic food, process for its preparation and management of intake |
WO2007084500A2 (en) * | 2006-01-13 | 2007-07-26 | Advanced Bionutrition Corporation | Continuous spray-capture production system |
PL2040567T3 (en) * | 2006-06-30 | 2014-11-28 | Lars Edebo | Zygomycetes for fish feed |
WO2008027235A1 (en) * | 2006-08-25 | 2008-03-06 | University Of New Mexico | Methods and compositions for control of disease in aquaculture |
CA2673120C (en) | 2006-12-18 | 2012-08-07 | Advanced Bionutrition Corporation | A dry food product containing live probiotic |
GB2477712A (en) | 2006-12-20 | 2011-08-17 | Advanced Bionutrition Corp | Antigenicity of infectious pancreatic necrosis virus VP2 sub-viral particles expressed in yeast |
US20110020494A1 (en) * | 2007-10-30 | 2011-01-27 | Lars Petersen | Growth medium for lactic acid bacteria |
US20130323801A1 (en) * | 2007-11-01 | 2013-12-05 | Wake Forest University School Of Medicine | Compositions, Methods, and Kits for Polyunsaturated Fatty Acids from Microalgae |
US8778384B2 (en) | 2008-03-24 | 2014-07-15 | Advanced Bionutrition Corporation | Compositions and methods for encapsulating vaccines for the oral vaccination and boostering of fish and other animals |
US7998502B2 (en) | 2008-03-24 | 2011-08-16 | Advanced Bionutrition Corp. | Encapsulated vaccines for the oral vaccination and boostering of fish and other animals |
WO2010051489A1 (en) * | 2008-10-31 | 2010-05-06 | Sapphire Energy, Inc. | Animal feedstock comprising genetically modified algae |
EP2410996B1 (en) | 2009-03-27 | 2017-08-02 | Advanced Bionutrition Corp. | Microparticulated vaccines for the oral or nasal vaccination and boostering of animals including fish |
CN102459568A (en) | 2009-05-26 | 2012-05-16 | 先进生物营养公司 | Stable dry powder composition comprising biologically active microorganisms and/or bioactive materials and methods of making |
PL2529004T3 (en) | 2010-01-28 | 2017-12-29 | Advanced Bionutrition Corporation | Dry glassy composition comprising a bioactive material |
US9504750B2 (en) | 2010-01-28 | 2016-11-29 | Advanced Bionutrition Corporation | Stabilizing composition for biological materials |
AU2011289272B2 (en) | 2010-08-13 | 2015-02-05 | Advanced Bionutrition Corporation | Dry storage stabilizing composition for biological materials |
FR2964014B1 (en) * | 2010-08-31 | 2013-04-05 | Ifremer | NUCLEUS COATED WITH A FILMOGENEOUS COATING WITH ANTIBACTERIAL AND CICATRISANT PROPERTIES AND METHOD OF OBTAINING THE SAME |
US8758774B2 (en) * | 2012-07-20 | 2014-06-24 | Kuwait Institute For Scientific Research | Bivalent vaccine for marine fish and method for making the same |
JP6275143B2 (en) | 2012-08-23 | 2018-02-07 | トランサルガエ イスラエル リミテッド | Genetically modified microalgae and their use for oral delivery of proteins |
WO2015121863A1 (en) | 2014-02-12 | 2015-08-20 | Transalgae Israel Ltd. | Algal based edible vaccines |
CN104313104B (en) * | 2014-09-26 | 2017-05-24 | 江苏农林职业技术学院 | Ionic protein peptide and preparation method and application thereof |
AU2016297986B8 (en) | 2015-07-29 | 2020-06-11 | Advanced Bionutrition Corp. | Stable dry probiotic compositions for special dietary uses |
WO2023245240A1 (en) * | 2022-06-22 | 2023-12-28 | Provectus Algae Pty Ltd | Promotion of synchronous sexual maturation and spawning in aquatic animals |
Family Cites Families (75)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5328989B2 (en) * | 1974-05-27 | 1978-08-17 | ||
USRE32333E (en) * | 1978-10-16 | 1987-01-20 | Eli Lilly And Company | A-21978 Antibiotics and process for their production |
IL70022A0 (en) * | 1982-11-08 | 1984-01-31 | Standard Oil Co | Method for introducing foreign genes into green algae cells utilizing t-dna of agrobacterium |
LU85967A1 (en) * | 1985-06-20 | 1987-01-13 | Oleofina Sa | PROCESS FOR THE PREPARATION OF NEW YEASTS AS FEED COMPOUNDS FOR FISH |
US5281596A (en) | 1986-02-19 | 1994-01-25 | Bayer Aktiengesellschaft | Antibacterial drugs for fish |
JPS62224297A (en) * | 1986-03-25 | 1987-10-02 | Kyowa Hakko Kogyo Co Ltd | Production of growth hormone polypeptide of fish or such |
US5062122A (en) * | 1988-09-28 | 1991-10-29 | Kenwood Corporation | Delay-locked loop circuit in spread spectrum receiver |
EP0387457A1 (en) * | 1989-01-06 | 1990-09-19 | Eurogentec S.A. | Recombinant fish hormone proteins |
FR2663326B2 (en) | 1989-11-17 | 1992-10-16 | Sanofi Sa | PYRIDAZINE DERIVATIVES, PREPARATION METHOD AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME. |
EP0384058A1 (en) * | 1989-02-09 | 1990-08-29 | Development Center For Biotechnology | Isolation of hepatitis B surface antigen from transformed yeast cells |
JP2786888B2 (en) * | 1989-05-30 | 1998-08-13 | マルハ株式会社 | Method for producing fish growth hormone |
US5407957A (en) * | 1990-02-13 | 1995-04-18 | Martek Corporation | Production of docosahexaenoic acid by dinoflagellates |
US5995443A (en) * | 1990-04-18 | 1999-11-30 | Rambus Inc. | Synchronous memory device |
IL96808A (en) * | 1990-04-18 | 1996-03-31 | Rambus Inc | Integrated circuit i/o using a high performance bus interface |
US5474769A (en) * | 1991-03-08 | 1995-12-12 | Sterling Winthrop Inc. | Treatment of microbial infection by monocyte stimulation with interleukin-7 |
US5270175A (en) * | 1991-07-12 | 1993-12-14 | Dna Plant Technology Corporation | Methods and compositions for producing metabolic products for algae |
GB9307408D0 (en) * | 1993-04-08 | 1993-06-02 | Danisco | Transgenic plants |
US5830463A (en) * | 1993-07-07 | 1998-11-03 | University Technology Corporation | Yeast-based delivery vehicles |
US5661017A (en) * | 1993-09-14 | 1997-08-26 | Dunahay; Terri Goodman | Method to transform algae, materials therefor, and products produced thereby |
JPH10503643A (en) * | 1994-06-17 | 1998-04-07 | ネーデルランセ オルハニサチエ フォール トゥーヘパスト−ナツールウェーテンシャッペルック オンデルズク テーエヌオー | Method for introducing genetic material into microorganism and transformant obtained by the method |
GB9521568D0 (en) * | 1995-10-20 | 1995-12-20 | Lynxvale Ltd | Delivery of biologically active polypeptides |
KR100195833B1 (en) * | 1995-12-07 | 1999-06-15 | 윤종용 | Self checking method for facsimile |
US5729399A (en) | 1995-12-13 | 1998-03-17 | International Business Machines Corporation | Contact start/stop disk drive with minimized head-disk wear in textured landing zone |
WO1997039106A1 (en) * | 1996-04-12 | 1997-10-23 | Martek Biosciences Corporation | Methods and tools for transformation of eukaryotic algae |
GB2316082A (en) * | 1996-08-13 | 1998-02-18 | Finnfeeds Int Ltd | Phytase |
JPH10150984A (en) * | 1996-11-19 | 1998-06-09 | Hagiwara Yoshihide | Production of antibody molecule |
USRE39350E1 (en) * | 1997-01-17 | 2006-10-17 | The Scripps Research Institute | RNA binding protein and binding site useful for expression of recombinant molecules |
US6125157A (en) * | 1997-02-06 | 2000-09-26 | Rambus, Inc. | Delay-locked loop circuitry for clock delay adjustment |
WO1998042748A1 (en) | 1997-03-24 | 1998-10-01 | Hih.Biocenter Inc. | New synthetic polypeptide |
US6537558B2 (en) * | 1997-03-31 | 2003-03-25 | Megan Health, Inc. | Methods of producing and using virulence attenuated poxR mutant bacteria |
US5968809A (en) * | 1997-04-11 | 1999-10-19 | Abbot Laboratories | Methods and compositions for synthesis of long chain poly-unsaturated fatty acids |
US6173432B1 (en) * | 1997-06-20 | 2001-01-09 | Micron Technology, Inc. | Method and apparatus for generating a sequence of clock signals |
US6011732A (en) * | 1997-08-20 | 2000-01-04 | Micron Technology, Inc. | Synchronous clock generator including a compound delay-locked loop |
EP0954978B1 (en) * | 1998-03-12 | 2011-11-30 | VHsquared Limited | New products comprising inactivated yeasts or moulds provided with active antibodies |
US6100388A (en) * | 1998-03-16 | 2000-08-08 | Biogaia Biologies Ab | Lactobacilli harboring aggregation gene as a vaccine delivery vehicle |
US6451572B1 (en) * | 1998-06-25 | 2002-09-17 | Cornell Research Foundation, Inc. | Overexpression of phytase genes in yeast systems |
US6327318B1 (en) * | 1998-06-30 | 2001-12-04 | Mosaid Technologies Incorporated | Process, voltage, temperature independent switched delay compensation scheme |
US6462027B2 (en) * | 1998-07-06 | 2002-10-08 | University Of Georgia Research Foundation, Inc. | Delivery of nucleic acid into aquatic animals |
US6399074B1 (en) | 1998-07-24 | 2002-06-04 | Megan Health, Inc. | Live attenuated salmonella vaccines to control avian pathogens |
US6107826A (en) * | 1998-08-19 | 2000-08-22 | Xilinx, Inc. | Interconnect structure for FPGA with configurable delay locked loop |
KR100275753B1 (en) * | 1998-11-30 | 2000-12-15 | 윤종용 | Jitter correction apparatus and method in a television system |
US6449738B1 (en) * | 1998-12-03 | 2002-09-10 | International Business Machines Corporation | Apparatus for bus frequency independent wrap I/O testing and method therefor |
US20020041196A1 (en) * | 1999-02-12 | 2002-04-11 | Paul Demone | Delay locked loop |
US6777995B1 (en) * | 1999-02-26 | 2004-08-17 | Micron Technology, Inc. | Interlaced delay-locked loops for controlling memory-circuit timing |
US6397361B1 (en) * | 1999-04-02 | 2002-05-28 | International Business Machines Corporation | Reduced-pin integrated circuit I/O test |
US6421801B1 (en) * | 1999-06-08 | 2002-07-16 | Intel Corporation | Testing IO timing in a delay locked system using separate transmit and receive loops |
US6476652B1 (en) * | 1999-11-01 | 2002-11-05 | Hynix Semiconductor Inc. | Delay locked loop for use in synchronous dynamic random access memory |
US6477674B1 (en) * | 1999-12-29 | 2002-11-05 | Intel Corporation | Method and apparatus for conducting input/output loop back tests using a local pattern generator and delay elements |
US6429715B1 (en) * | 2000-01-13 | 2002-08-06 | Xilinx, Inc. | Deskewing clock signals for off-chip devices |
US6754613B2 (en) * | 2000-03-17 | 2004-06-22 | Vector 12 Corporation | High resolution time-to-digital converter |
JP3467446B2 (en) * | 2000-03-30 | 2003-11-17 | Necエレクトロニクス株式会社 | Digital phase control circuit |
KR100366618B1 (en) * | 2000-03-31 | 2003-01-09 | 삼성전자 주식회사 | Delay locked loop circuit for correcting duty cycle of clock signal and delay locking method |
US6445231B1 (en) * | 2000-06-01 | 2002-09-03 | Micron Technology, Inc. | Digital dual-loop DLL design using coarse and fine loops |
CA2415319A1 (en) | 2000-06-16 | 2001-12-20 | Martek Biosciences Corporation | Recombinant phycobiliprotein and phycobiliprotein linker fusion proteins and uses therefore |
AU2001269936A1 (en) | 2000-06-20 | 2002-01-02 | Phycotransgenics, Llc | Transgenic algae for delivering antigens to an animal |
US6502050B1 (en) * | 2000-06-20 | 2002-12-31 | Xilinx, Inc. | Measuring a minimum lock frequency for a delay locked loop |
US6737262B1 (en) * | 2000-07-11 | 2004-05-18 | Robert I. Bolla | Animal feed containing polypeptides |
US6771694B1 (en) * | 2000-07-12 | 2004-08-03 | International Business Machines Corporation | Speed negotiation for serial transceivers |
JP4454810B2 (en) * | 2000-08-04 | 2010-04-21 | Necエレクトロニクス株式会社 | Digital phase control method and digital phase control circuit |
AU2001295501A1 (en) | 2000-08-22 | 2002-03-04 | Arimedes Biotechnology Gmbh | Foodstuff and animal feedstuff supplement compositions |
US6687780B1 (en) * | 2000-11-02 | 2004-02-03 | Rambus Inc. | Expandable slave device system |
US6671847B1 (en) * | 2000-11-08 | 2003-12-30 | Intel Corporation | I/O device testing method and apparatus |
CA2428027C (en) * | 2000-11-11 | 2012-09-11 | The University Court Of The University Of Aberdeen | Yeast derived vaccine against ipnv |
US6857080B1 (en) * | 2001-01-08 | 2005-02-15 | Pixelworks, Inc. | Multi-link receiver mechanism for processing multiple data streams |
JP4526194B2 (en) * | 2001-01-11 | 2010-08-18 | ルネサスエレクトロニクス株式会社 | Oversampling clock recovery method and circuit |
DE60227498D1 (en) | 2001-03-23 | 2008-08-21 | Advanced Bionutrition Corp | DISTRIBUTION OF AGENTS FOR THE CONTROL OF AFFECTS IN AQUACULTURE USING BIOACTIVE PROTEINS CONTAINING YEAST |
US6839860B2 (en) * | 2001-04-19 | 2005-01-04 | Mircon Technology, Inc. | Capture clock generator using master and slave delay locked loops |
CA2457349A1 (en) * | 2001-08-10 | 2003-02-20 | University Of Maryland Biotechnology Institute | Sub-unit vaccine for infectious pancreatic necrosis virus |
JP4609808B2 (en) * | 2001-09-19 | 2011-01-12 | エルピーダメモリ株式会社 | Semiconductor integrated circuit device and delay lock loop device |
US6580304B1 (en) * | 2002-03-28 | 2003-06-17 | M/A-Com, Inc. | Apparatus and method for introducing signal delay |
KR100470995B1 (en) * | 2002-04-23 | 2005-03-08 | 삼성전자주식회사 | multi clock domain data input processing device having clock receiving locked loop and method for providing clock signals therefore |
KR100486256B1 (en) * | 2002-09-04 | 2005-05-03 | 삼성전자주식회사 | Semiconductor memory device comprising duty cycle correction circuit and circuit of interpolating clock signals in the semiconductor memory device |
US6865135B2 (en) * | 2003-03-12 | 2005-03-08 | Micron Technology, Inc. | Multi-frequency synchronizing clock signal generator |
US8934597B2 (en) * | 2003-03-12 | 2015-01-13 | Infineon Technologies Ag | Multiple delay locked loop integration system and method |
US7219269B2 (en) * | 2003-07-28 | 2007-05-15 | Credence Systems Corporation | Self-calibrating strobe signal generator |
-
2002
- 2002-03-22 DE DE60227498T patent/DE60227498D1/en not_active Expired - Lifetime
- 2002-03-22 MX MXPA03008563A patent/MXPA03008563A/en not_active Application Discontinuation
- 2002-03-22 NZ NZ528578A patent/NZ528578A/en unknown
- 2002-03-22 JP JP2002574907A patent/JP2004532628A/en active Pending
- 2002-03-22 EP EP04030875A patent/EP1541036A1/en not_active Withdrawn
- 2002-03-22 EP EP04030873A patent/EP1559327B1/en not_active Expired - Lifetime
- 2002-03-22 AT AT02725276T patent/ATE400189T1/en not_active IP Right Cessation
- 2002-03-22 AT AT04030873T patent/ATE467358T1/en not_active IP Right Cessation
- 2002-03-22 EP EP04030874A patent/EP1559328A1/en not_active Withdrawn
- 2002-03-22 DE DE60236374T patent/DE60236374D1/en not_active Expired - Lifetime
- 2002-03-22 AU AU2002255851A patent/AU2002255851B2/en not_active Ceased
- 2002-03-22 WO PCT/US2002/008651 patent/WO2002076391A2/en active Application Filing
- 2002-03-22 CA CA002442004A patent/CA2442004A1/en not_active Abandoned
- 2002-03-22 EP EP02725276A patent/EP1381345B1/en not_active Expired - Lifetime
-
2003
- 2003-09-05 US US10/654,985 patent/US20040047881A1/en not_active Abandoned
- 2003-09-23 NO NO20034244A patent/NO20034244L/en not_active Application Discontinuation
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2006
- 2006-06-09 US US11/449,829 patent/US8198067B2/en not_active Expired - Fee Related
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