WO1998018453A1 - Vaccins oraux pour jeunes animaux, avec enrobage gastro-resistant - Google Patents

Vaccins oraux pour jeunes animaux, avec enrobage gastro-resistant Download PDF

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Publication number
WO1998018453A1
WO1998018453A1 PCT/IB1997/001136 IB9701136W WO9818453A1 WO 1998018453 A1 WO1998018453 A1 WO 1998018453A1 IB 9701136 W IB9701136 W IB 9701136W WO 9818453 A1 WO9818453 A1 WO 9818453A1
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Prior art keywords
antigen
pathogen
canine
vaccine
animal
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PCT/IB1997/001136
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English (en)
Inventor
Jay Dean Gerber
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Pfizer Inc.
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Publication date
Application filed by Pfizer Inc. filed Critical Pfizer Inc.
Priority to AU41333/97A priority Critical patent/AU4133397A/en
Publication of WO1998018453A1 publication Critical patent/WO1998018453A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/215—Coronaviridae, e.g. avian infectious bronchitis virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/15—Reoviridae, e.g. calf diarrhea virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/155—Paramyxoviridae, e.g. parainfluenza virus
    • A61K39/175—Canine distemper virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/23—Parvoviridae, e.g. feline panleukopenia virus
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A61K9/2846—Poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5254—Virus 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
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A61K2039/541—Mucosal route
    • A61K2039/542—Mucosal route oral/gastrointestinal
    • 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
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2720/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsRNA viruses
    • C12N2720/00011—Details
    • C12N2720/12011—Reoviridae
    • C12N2720/12311—Rotavirus, e.g. rotavirus A
    • C12N2720/12334—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14311—Parvovirus, e.g. minute virus of mice
    • C12N2750/14334—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/20011—Coronaviridae
    • C12N2770/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • the present invention relates to compositions and methods for oral vaccination of animals of weaning age or younger against disease
  • Vaccination of animals of weaning age or younger against a disease-causing pathogen is often compromised by the presence of interfering maternal antibodies, i e , maternally-derived antibodies that are directed against the pathogen
  • interfering maternal antibodies i e
  • CDV canine distemper virus
  • CCV canine coronavirus
  • CRV canine rotavirus
  • CPV canine parvovirus
  • CDV canine coronavirus
  • CRV canine rotavirus
  • vaccination of these young dogs against these viral pathogens is compromised by the presence of the interfering maternal antibodies This creates a "window of susceptibility" to infection in the young animal because the maternal antibody titer in the animal is often high enough to interfere with vaccination, but too low to provide an adequate level of protection
  • Parenterally-injected vaccines are of less than optimal efficacy in the ⁇ e young animals, and must generally be administered multiple times to ensure adequate immunity
  • parenterally-injected vaccines often do
  • oral immunization may trigger a more rapid and robust immune response against one or more of these pathogens by eliciting the production of secretory immunoglobulin A (IgA) antibodies at mucosal sites
  • IgA secretory immunoglobulin A
  • Such an immune response is triggered when an antigen is presented to the epithelium of gut-associated lymphoid tissues, such as Peyer's patches See, for example, O'Hagan, 1992, Clin Pharmacokinet 22 1 -10, Caldwell et al , 1982, J Pharm Pharmacol 34 520, and U S Pat No 5,075, 109
  • oral immunization has generally remained underexploited as a method of vaccination because major problems remain over how to deliver an oral vaccine to the gut mucosal tissue without significant degradation in the digestive tract (O'Hagan, 1992, above)
  • U S Pat No 5,352,448 discloses an oral vaccine formulation for ruminants, comprising an antigen composition in a delivery vehicle consisting of a water-swellable hydrogel matrix, which allows for delivery of the antigen to mucosa-associated lymphoid tissue in the post-ruminal portion of the digestive tract
  • U S Pat No 5,176,909 discloses compositions for oral administration to humans or animals, comprising an immunogen, gelatin of a particular molecular weight range, and an enteric coating
  • U S Pat No 5,075,109 discloses a method for targeting a bioactive agent, e g , an antigen, to the Peyer's patches by microencapsulating the agent in a biocompatible polymer or copolymer, such as poly(DL-lact ⁇ de-co-glycol ⁇ de)
  • U S Pat No 5,032,405 discloses an oral formulation, comprising a lyophilized mixture of a biologically active agent,
  • the invention provides an oral vaccine formulation for administration to an animal of weaning age or younger, which comprises an immunologically effective amount of an antigen in an enteric coating, and that it is capable of triggering a protective immune response against a pathogen in the presence of interfering maternal antibodies
  • the protective immune response can be triggered in animals at a younger age than can be obtained with conventional parenteral vaccines
  • the invention provides a method for vaccinating an animal of weaning age or younger against a disease, comprising orally administering to the animal a vaccine comprising an immunologically effective amount of an antigen in an enteric coating, which vaccine is capable of triggering a protective immune response against the disease, even in the presence of interfesing maternal antibodies
  • the animal is a dog of weaning age or younger, although the invention is generally applicable to other animals of weaning age or younger, including cats, cows, pigs, sheep, and horses, among others.
  • the present invention provides an oral vaccine against a pathogen for administration to an animal of weaning age or younger, which vaccine comprises an immunologically effective amount of an antigen prepared from the pathogen in an enteric coating, that it is capable of triggering a protective immune response against the pathogen in the presence of interfering maternal antibodies
  • the vaccine may be administered to any animal of weaning age or younger of a particular species, whether or not interfering maternal antibodies are present
  • the vaccine of the invention may be formulated for administration to any one of various species of animals, including dogs, cats, cows, pigs, sheep, and horses, among others
  • the animal is a dog of weaning age or younger
  • the pathogen is a canine virus
  • the enteric coating protects the antigen from the low pH environment of the stomach, but dissolves and releases the antigen in the region of gut-associated lymphoid tissues As a result, a gut mucosal immune response is triggered in the animal that is sufficiently robust to overcome the interference of maternal antibodies and
  • the antigen may be prepared from any pathogen that causes disease in cows including, for example, bovine herpes virus, bovine respiratory syncitial virus, bovine diarrhea virus, parainfluenza type 3 virus, bovine coronavirus, bovine rotavirus, rabies virus, and E coll, among others
  • the antigen may be prepared from any pathogen that causes disease in pigs, including, for example, swine parvovirus, swine pseudorabies virus, rabies virus, transmissible gastroenteritis virus, swine rotavirus, and virulent E coll, among others
  • the antigen may comprise any component of a viral or cellular pathogen, which component is capable of triggering a protective immune response in the animal in the presence of interfering maternal antibodies
  • a component includes, but is not limited to, whole viral particles or cells, viral capsids and envelopes, whole membrane preparations and membrane fractions, proteins, peptides, glycoproteins, exotoxins, endotoxins, enzymes, and antigenic subunits of any of the aforementioned components
  • a DNA sequence which encodes an antigenic peptide or protein Smaller antigenic components may be derived from larger components such as membranes and proteins by fractionation or degradation techniques known in the art Once obtained, the antigen may be modified using standard techniques, for example, by adding or substituting chemical substituents that alter rates of degradation in vivo or that increase antigenicity
  • the antigen may also be further processed, such as by lyophihzation, according to standard techniques
  • Pathogenic strains of viral particles or cells for use to prepare antigen can be obtained using standard isolation techniques from fluids, tissues or organs of infected animals exhibiting clinical symptoms of a particular disease
  • Alternative sources of pathogen include publicly available deposits, such as those stored at the American Type Culture Collection (ATCC), 12301 Parklawn Drive, Rockville, Maryland, 20852-1776, USA
  • a pathogen may be serially passaged in an in vitro culture of susceptible cells, preferably mammalian cells, and most preferably in cells of the particular animal species to be vaccinated
  • a canine viral pathogen can be serially cultured in canine kidney cells according to known techniques, such as those described in Appel ef al , 1979, Vet Records 105 156-159, U S Pat No 4,193,991 , and U S Pat No 4,303,645, which are incorporated herein by reference
  • Other methods of attenuation include, but are not limited to, exposure of a pathogen to a mutagenic agent, e g , a chemical mutagen or ultraviolet radiation
  • a pathogen may also be attenuated by knocking out one or more essential metabolic
  • the oral vaccine formulation of the invention comprises an immunologically effective amount of antigen, which is that amount of antigen capable of triggering a protective immune response in an animal of weaning age or younger in the presence of interfering maternal antibodies
  • a "protective immune response” is defined as any immunological response, based either on antibody or cell-mediated immunity, or both, occurring in the animal after administration of the vaccine of the invention, which response either prevents or reduces infection by the pathogen, or eliminates or reduces the severity, or slows the rate of progression, of one or more clinical symptoms or conditions normally associated with a disease caused by the pathogen
  • interfering maternal antibodies refer to those antibodies present in the young animal that originate from a maternal source, are directed against a pathogen, and are present in sufficient titer to otherwise detectably reduce, or interfere with, the efficacy of a parenterally administered vaccine directed against the pathogen For example, a titer of interfering maternal antibodies of about 1 16 or higher will interfere with successful immunization
  • the oral vaccine formulation of the invention
  • the oral vaccine formulation of the invention may further comprise one or more veterina ⁇ ly-acceptable excipients known in the art, such as those that improve preparation, handling and stability of the formulation
  • excipients include, for example, lactose, sucrose, maltose, mannitol, starch, gums, gelatin, cellulose derivatives, magnesium salts such as magnesium stearate, magnesium carbonate, and magnesium oxide, calcium salts such as calcium carbonate and calcium sulfate, silica gel, and talc, among others
  • the oral vaccine formulation may optionally comprise other useful components, including, for example, an undercoating, or a colorful dye
  • an oral vaccine formulation comprises the following components antigen, lactose, magnesium stearate, modified cellulose gum, an undercoating, and an enteric coating
  • Suitable other vehicles and additives are known, or will be apparent to those of skill in the art See, e g , Remington's Pharmaceutical Science, 18th Ed , 1990, Mack Publishing, which is incorporated herein by reference
  • the ingredients of the vaccine are combined according to known techniques to produce an orally administrable formulation
  • the mixture is compressed to an administrable form such as a tablet, pill, or capsule
  • the formulation may be compressed using a Carver Lab Press (Fred S Carver Inc , Menomee Falls, Wl )
  • the formulation is then provided with an enteric coating such as by the Open-Pan Ladle Coating Process or the Wurster Coating Process, which are well-known in
  • An effective dosage of the oral vaccine formulation may be determined by conventional means, starting with a low dose of the formulation and then increasing the dosage while monitoring the effects, and systematically varying the dose as well Numerous factors may be taken into consideration when determining an optimal dose per animal Primary among these is the breed, size, age, and general condition of the animal to be vaccinated Other considerations include the presence and titer of interfering maternal antibodies in the animal, the presence of other drugs, and the like The actual dose is preferably chosen after consideration of the results of other animal studies
  • an immunologically effective amount of vaccine comprising a viral pathogen will comprise from about 10 3 to about 10 9 TCID 50 per animal, more preferably the amount will be from about 10" to about 10 8 TCID 50 per animal, and most preferably the amount will be from about 10 5 5 to about 10 7 TCID 50 per animal
  • an effective dose range of bacteria will comprise from about 10 5 to about 10 12 plaque-forming units (pfu) per animal
  • Vaccine regimens may also be selected based on the above-described factors Thus, animals may be vaccinated soon after birth, or just prior to, at the time of, or soon after weaning, depending upon analysis of these factors
  • a benefit of the vaccine of the present invention is that a protective immune response can be triggered in animals at a younger age than can generally be obtained with conventional parenteral vaccines
  • conventional parenteral vaccines often do not induce immunity prior to 12 to 16 weeks of age depending on maternal antibody titer
  • the oral vaccine of the invention can induce immunity at 4-6 weeks of age
  • administration schedule is a single oral dose of the vaccine at the time of weaning / e , at approximately 4 to 8 weeks of age
  • two oral doses may be necessary if an adequate immune response does not occur in a dog after an initial dose, or if the dog has an interfering maternal antibody titer in excess of about 1/128
  • the present invention further provides combination vaccines, comprising an immunologically effective amount of a first antigen capable of triggering a protective immune response against a pathogen in the presence of maternal antibodies, and an immunologically effective amount of one or more other antigens that can trigger a protective immune response against the same or a difference pathogen
  • a general oral formulation was prepared as follows A ratio by weight of 60 parts lactose (direct compression grade) (Sheffield Products, Norwich, N Y ), I part AC-DI-SOL ® modified cellulose gum (FMC Corp , Philadelphia, PA ), 1 part magnesium stearate (impalpable powder) (Mallinckrodt, St Louis, MO ), and 4 parts lyophi zed canine parvovirus that had been attenuated by serial passage in dog kidney cells, were used to make a tablet formulation
  • the lactose, modified cellulose gum and lyophihzed vaccine were mixed together
  • the magnesium stearate was added to produce a final mixture, which was compressed into tablets using a Carver Lab Press (Fred S Carver Inc , Menomee Falls, Wl ) with a one-half inch tooling dye at 5,000 pounds/sq inch
  • the tablets were rotated in a pan coater during application of OPADRY CLEAR TM undercoating (Colorcon, West Point, PA
  • EXAMPLE 2 EFFICACY TESTING OF AN ORAL FORMULATION WITHOUT AN ENTERIC COATING
  • Attenuated CPV, CCV and CRV were grown separately in cultures of canine kidney cells to titers of 10 6 7 TCID 50 of CPV, 10 5 3 TCID 50 of CCV, and 10 8 2 TCID 50 of
  • CRV CRV
  • the attenuated viral particles were lyophihzed and formulated together into tablets comprising 10 6 3 TCID 50 of CPV, 10 4 3 TCID 50 of CCV, and 10 7 5 TCID 50 of CRV, and containing all of the components listed above in Example 1 , but without an enteric coating
  • Attenuated CPV (10" TCID 50 ) and CCV (10 J ' TCID 50 ) were formulated together into tablets as above in Example 2, but with an enteric coating, comprising about 3% (v/v) EUDRAGIT S100 ® , that dissolves only at about pH 6 0 or higher
  • enteric coating comprising about 3% (v/v) EUDRAGIT S100 ® , that dissolves only at about pH 6 0 or higher
  • Twenty 7-week-old SPF beagles, seronegative for CPV and CCV were distributed into two groups of 10 dogs each, taking litter distribution into consideration
  • the ten dogs in the first group (vaccinates) (Table 2) each received a single dose of the vaccine by placing a single tablet in the back of the mouth and gently pushing it into the throat for the dog to swallow
  • the ten dogs in the second group were not vaccinated (Table 3) Serum samples were collected prior to vaccination and for 5 weeks post-vaccination for CPV virus neutralization testing and CCV
  • Vaccinates were observed daily for 5 days post-vaccination for signs of vomiting, depression and diarrhea In addition, temperatures were taken daily for 5 days post-vaccination, and blood collected once a week for CBC, acute-phase protein, and immune cell marker analyses None of the vaccinates showed any signs of vomiting, diarrhea, depression, or a febrile response Furthermore, none of the vaccinates showed any alpha-1 glycoprotein abnormalities, abnormal immune cell marker profiles, or abnormal blood profiles Thus, the vaccine appears to be safe
  • a serum neutralizing antibody titer equal to or greater than 1 16 is considered sufficient to protect against virulent CPV challenge (see 9 C F R ⁇ 113 317)
  • a Geometrical mean titer
  • EXAMPLE 4 RESPONSE OF DOGS WITH MATERNAL ANTI-CPV ANTIBODIES TO ORAL CPV VACCINATION
  • Tables 4 and 5 demonstrate that the enteric-coated oral vaccine formulation of the invention immunizes dogs of weaning age against CPV infection in the presence of maternal anti-CPV antibody titers of up to 1 128 Out of four dogs with interfering maternal antibody titers of 1 128 (BGZ, BKY, BLY, CYZ), three (BGZ, BKY, BLY) developed strong serum-neutralizing antibody titers after a single oral dose of the vaccine A second dose may be required for dogs having interfering maternal antibody titers greater than 1 128

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  • Health & Medical Sciences (AREA)
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  • Virology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Mycology (AREA)
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  • Pulmonology (AREA)
  • Engineering & Computer Science (AREA)
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Abstract

L'invention concerne une formulation de vaccin et une methode de vaccination orale contre un pathogène, destinées à des animaux en période de sevrage ou plus jeunes, en présence d'anticorps maternels perturbant la réaction immunitaire desdits animaux. La formulation de l'invention comprend un antigène protégé par un enrobage gastro-résistant.
PCT/IB1997/001136 1996-10-28 1997-09-22 Vaccins oraux pour jeunes animaux, avec enrobage gastro-resistant WO1998018453A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU41333/97A AU4133397A (en) 1996-10-28 1997-09-22 Oral vaccines for young animals with an enteric coating

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US2880296P 1996-10-28 1996-10-28
US60/028,802 1996-10-28

Publications (1)

Publication Number Publication Date
WO1998018453A1 true WO1998018453A1 (fr) 1998-05-07

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PCT/IB1997/001136 WO1998018453A1 (fr) 1996-10-28 1997-09-22 Vaccins oraux pour jeunes animaux, avec enrobage gastro-resistant

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AR (1) AR010031A1 (fr)
AU (1) AU4133397A (fr)
WO (1) WO1998018453A1 (fr)
ZA (1) ZA979592B (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003507414A (ja) * 1999-08-24 2003-02-25 テバ ファーマシューティカル インダストリーズ リミティド ワクチン組成物およびその使用方法
EP1370285A2 (fr) * 2001-02-28 2003-12-17 Teva Pharmaceutical Industries Ltd. Composition de vaccin et procede d'utilisation associe
WO2004056390A1 (fr) * 2002-12-19 2004-07-08 Akzo Nobel Patent Department Vaccin trivalent a transfert d'anticorps maternels par l'intermediaire du lait
JP2008169207A (ja) * 2006-12-27 2008-07-24 Pfizer Prod Inc ワクチン投与方法
EP2453916A1 (fr) * 2009-07-17 2012-05-23 The Board Of Regents For Oklahoma State University Vaccins supralinguaux et applicateurs supralinguaux
WO2013151595A1 (fr) * 2012-04-04 2013-10-10 Vaxform Llc Système adjuvant amélioré pour vaccin administré par voie orale
CN106460050A (zh) * 2014-04-28 2017-02-22 西格马-奥尔德里奇有限责任公司 使用靶向核酸内切酶进行哺乳动物基因组的表观遗传修饰
JP2017506265A (ja) * 2014-02-20 2017-03-02 バクサート インコーポレイテッド 小腸送達のための製剤
EP3566716A1 (fr) * 2013-09-27 2019-11-13 Intervet International B.V. Formulations sèches de vaccins parvovirus stables à température ambiante
US11433146B2 (en) 2015-06-12 2022-09-06 Vaxart, Inc. Formulations for small intestinal delivery of RSV and norovirus antigens

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EP0181117A2 (fr) * 1984-11-01 1986-05-14 American Home Products Corporation Vaccins oraux
EP0420459A2 (fr) * 1989-09-27 1991-04-03 Warner-Lambert Company Composition pharmaceutique orale pour des substances protéiniques sensibles aux acides
RU2045960C1 (ru) * 1992-07-01 1995-10-20 Соболева Галина Леонидовна Вакцина для профилактики чумы, инфекционного гепатита, аденовироза, парвовирусного энтерита и лептоспироза собак

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DATABASE WPI Section Ch Week 9625, Derwent World Patents Index; Class B04, AN 96-249761, XP002052233 *

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003507414A (ja) * 1999-08-24 2003-02-25 テバ ファーマシューティカル インダストリーズ リミティド ワクチン組成物およびその使用方法
EP1370285A4 (fr) * 2001-02-28 2005-04-13 Teva Pharma Composition de vaccin et procede d'utilisation associe
EP1370285A2 (fr) * 2001-02-28 2003-12-17 Teva Pharmaceutical Industries Ltd. Composition de vaccin et procede d'utilisation associe
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