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WO2006056841A1 - Vaccins multisouches a base de mycoplasma hyopneumoniae - Google Patents

Vaccins multisouches a base de mycoplasma hyopneumoniae Download PDF

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Publication number
WO2006056841A1
WO2006056841A1 PCT/IB2005/003412 IB2005003412W WO2006056841A1 WO 2006056841 A1 WO2006056841 A1 WO 2006056841A1 IB 2005003412 W IB2005003412 W IB 2005003412W WO 2006056841 A1 WO2006056841 A1 WO 2006056841A1
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Prior art keywords
mycoplasma hyopneumoniae
strains
vaccine
animal
strain
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PCT/IB2005/003412
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English (en)
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Robin Lee Keich
David Ross Mcgavin
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Pharmacia & Upjohn Company Llc
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Publication of WO2006056841A1 publication Critical patent/WO2006056841A1/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
    • A61K39/02—Bacterial antigens
    • A61K39/0241—Mollicutes, e.g. Mycoplasma, Erysipelothrix

Definitions

  • This invention relates generally to animal health and vaccines.
  • this invention relates to vaccines against Mycoplasma hyopneumoniae prepared from two or more strains of Mycoplasma hyopneumoniae.
  • Mycoplasma hyopneumoniae is a swine respiratory pathogen that causes enzootic pneumonia, a chronic disease which affects swine of all ages but is most prevalent in growing and finishing swine. Infected pigs show symptoms of cough, fever and growth retardation. The economic impact of the disease is significant, as it is believed to be one of the most important causes of disease-associated loss in swine (Whittlestone, pp. 133-176, in TuIIy and Whitcomb (eds.), The Mycoplasmas V Ol 2: Human and Animal Mycoplasmas, New York, Academic Press, (1979)).
  • Mycoplasma hyopneumoniae The disease generally results in reduced feed efficiency, and affected swine are often prone to secondary infection by opportunistic organisms.
  • Mycoplasma hyopneumoniae remains a significant threat to the pig industry. It has been reported that some of the commercial vaccines can protect pigs against experimental Mycoplasma hyopneumoniae challenge, but cannot completely eliminate pneumonia or significantly reduce the colonization of the microorganism (Thacker et al., Swine Health and Production 6: 107-112, 1998). Thus, there remains a need for vaccines that effectively protect swine against infections caused by Mycoplasma hyopneumoniae.
  • the present invention is directed to vaccines prepared from multiple strains of Mycoplasma hyopneumoniae.
  • the present invention provides a vaccine prepared from at least two heterologous strains of Mycoplasma hyopneumoniae.
  • the heterologous strains differ in at least one characteristic at the genetic level, the protein level, or the level of virulence.
  • the vaccine can include bacterins prepared from the M. hyopneumoniae strains, i.e., inactivated whole or partial cell preparations of the M. hyopneumoniae strains.
  • the vaccine can include one or more immunogenic polypeptides or immunogenic peptide fragments thereof, prepared from the M. hyopneumoniae strains.
  • the vaccine can include one or more nucleic acid molecules encoding immunogenic polypeptides or immunogenic peptide fragments thereof from the M. hyopneumoniae strains.
  • the vaccine of the present invention further includes at least one immunogen prepared from a pathogen other than M. hyopneumoniae, e.g., a viral, bacterial or parasitic pathogen.
  • a pathogen other than M. hyopneumoniae e.g., a viral, bacterial or parasitic pathogen.
  • the vaccines provided in the present invention typically include a veterinary-acceptable carrier, for example, an appropriate adjuvant. Such vaccines can be administered to an animal for treating or preventing a disease caused by M. hyopneumoniae.
  • This invention comprises the following: A vaccine formulation for immunization of an animal comprising an effective amount of immunogens prepared from at least two heterologous Mycoplasma hyopneumoniae strains and a veterinary-acceptable carrier.
  • the vaccine formulation above wherein at least one of said two strains of said immunogens comprise an inactivated, whole or partial Mycoplasma hyopneumoniae cell preparation.
  • the vaccine herein wherein said cell preparation is inactivated by binary ethyleneimine (BEI).
  • the vaccine herein wherein said immunogens comprise one or more immunogenic polypeptides or fragments thereof from at least one of said two strains.
  • the vaccine formulation wherein said immunogenic polypeptides are selected from the group consisting of P44, P46, P50, P65, P70, P97, and P102.
  • the vaccine formulation herein wherein said immunogens comprise an inactivated, whole or partial Mycoplasma hyopneumoniae cell preparation of at least one strain and one or more immunogenic polypeptides or fragments thereof from at least one other strain.
  • the vaccine formulation described herein wherein said immunogens comprise one or more nucleic acids capable of expressing in said animal, one or more immunogenic polypeptides or fragments thereof from at least one of said two strains.
  • the vaccine formulation wherein said veterinary-acceptable carrier is an adjuvant.
  • the vaccine formulation wherein said adjuvant is the AMPHIGEN® formulation.
  • the vaccine formulation wherein said animal is a pig.
  • the vaccine formulation wherein the effective amount of immunogens from each Mycoplasma hyopneumoniae strain comprises from about 1 x10 6 to about 5x10 10 color changing units (CCU) per dose, or from about 1 x10 8 to about 5x10 10 color changing units (CCU) per dose, or from about 5x10 8 to about 5x10 10 color changing units (CCU) per dose.
  • a method of treating or preventing a disease in an animal caused by Mycoplasma hyopneumoniae comprising administering to the animal an effective amount of a vaccine comprising immunogens prepared from at least two heterologous Mycoplasma hyopneumoniae strains and a veterinary-acceptable carrier.
  • a vaccine comprising immunogens prepared from at least two heterologous Mycoplasma hyopneumoniae strains and a veterinary-acceptable carrier.
  • said immunogens comprise an inactivated, whole or partial Mycoplasma hyopneumoniae cell preparation of at least one of said two strains.
  • the method wherein said cell preparation is inactivated by binary ethyleneimine (BEI).
  • BEI binary ethyleneimine
  • said immunogens comprise one or more immunogenic polypeptides or fragments thereof from at least one of said two strains.
  • said immunogenic polypeptides are selected from the group consisting of P44, P46, P50, P65, P70, P97, and P102.
  • said immunogens comprise an inactivated, whole or partial Mycoplasma hyopneumoniae cell preparation of at least one strain and one or more immunogenic polypeptides or fragments thereof from at least one other strain.
  • said immunogens comprise one or more nucleic acids capable of expressing in said animal, one or more immunogenic polypeptides or fragments thereof from at least one of said two strains.
  • said immunogenic polypeptides are selected from the group consisting of P44, P46, P50, P65, P70, P97, and P102.
  • said veterinary-acceptable carrier is an adjuvant.
  • said adjuvant is the AMPHIGEN® formulation.
  • said animal is a pig.
  • the method wherein the effective amount of immunogens from each Mycoplasma hyopneumoniae strain comprises from about 1x10 6 to about 5x10 10 color changing units (CCU) per dose or from about 1 x10 8 to about 5x10 10 color changing units (CCU) per dose, or from about 5x10 8 to about 5x10 10 color changing units (CCU) per dose.
  • the method wherein the amount of said vaccine administered is from about 0.5 milliliters to about 3.0 milliliters, or more preferably from about 1.5 milliliters to about 2.5 milliliters.
  • the method wherein about two milliliters of the vaccine are administered as a single dose or two doses to a pig.
  • the method wherein the Mycoplasma hyopneumoniae vaccine is administered intranasally or intramuscularly.
  • a kit comprising a vaccine having Mycoplasma hyopneumoniae bacterins of at least two heterologous strains, the kit including an adjuvant.
  • the kit wherein said adjuvant is the AMPHIGEN® formulation.
  • the present invention is directed to vaccines prepared from multiple, i.e., at least two (i.e., two or more), heterologous strains of Mycoplasma hyopneumoniae, which provide more effective protection to vaccinated animals against infection caused by Mycoplasma hyopneumoniae, as compared to vaccines prepared from a single strain of Mycoplasma hyopneumoniae.
  • the incomplete protection provided by certain commercial Mycoplasma hyopneumoniae vaccines is due, at least in part, to the genetic and antigenic diversity among Mycoplasma hyopneumoniae strains. Therefore, by combining antigenic components from multiple Mycoplasma hyopneumoniae strains, the resulting vaccine compositions afford more effective protection against infection caused by Mycoplasma hyopneumoniae.
  • characteristics used herein in connection with a M. hyopneumoniae strain, include, e.g., the characteristics of the genetic materials, the characteristics of the proteins, and the virulence characteristics of a M. hyopneumoniae strain.
  • heterologous strains refer to strains that differ in one or more characteristics selected from genetic characteristics, protein characteristics, or virulence characteristics. By “more effective protection” is meant less likelihood for a pig to be infected with a given M. hyopneumoniae strain, less severe symptoms and faster recovery if the pig becomes infected, and/or less likelihood to suffer a secondary infection caused by an opportunistic organism.
  • strain or “isolate”, as used herein, refers to a M. hyopneumoniae cell, or a population of M. hyopneumoniae cells, which has characteristics that are commonly shared by cells of the same strain or isolate, but are distinct from those of cells of a different strain or isolate.
  • the characteristics of a strain at the protein level can manifest in the profile of total proteins, surface proteins, or glycoproteins of the strain, which can be determined by standard techniques such as SDS-PAGE, two-dimensional electrophoresis, and Western Blot, among others. See, e.g., Boh Chang Lin, supra.
  • the characteristics of a strain at the protein level can also manifest in the size, level or activity of a particular protein or antigen of the strain (Wise et al., pp.
  • the virulence or pathogenic characteristics of a strain can be evaluated based on clinical signs and body condition manifested in swine infected with the strain, e.g., coughing, elevated body temperature, lung lesion, symptoms of dyspnea and tachpnea, weight loss, and behavioral changes, among others.
  • M. hyo strains are known to those skilled in the art and are available from, e.g., the American Type Culture Collection, 10801 University Boulevard, Manassas, VA 20110-2209. These include for example: ATTC Nos. 25095, 25617, 25934, 27714 and 27715.
  • M. hyo isolates can also be obtained directly from naturally or experimentally infected animal (e.g., porcine) lung lesions using known techniques.
  • preferred vaccines of the present invention are prepared from multiple, i.e., two or more, strains of M. hyopneumoniae, which have been selected and determined to be heterologous, i.e., they differ from one another in at least one characteristic.
  • immunogenic materials are prepared from two or more strains.
  • the immunogenic materials can be in the form of an inactivated whole or partial M. hyo cell preparation, the form of polypeptide (i.e., one or more polypeptides or immunogenic fragments thereof, isolated from a M. hyo strain), or the form of nucleic acid (one or more nucleic acids encoding for one or more M. hyo derived polypeptides, or immunogenic fragments thereof, and which nucleic acids are capable of being expressed in vivo in an animal), or combinations thereof (e.g., a whole cell preparation of one strain combined with a immunogenic polypeptide from another strain).
  • the immunogenic materials from one M. hyo strain can be prepared independently from other strains to be used in a vaccine. Alternatively, cells of two or more strains can be combined before the preparation of immunogenic materials from the combined cells.
  • immunogenic refers to the capacity of a composition to provoke an immune response in an animal against the composition.
  • the immune response can be a cellular immune response mediated primarily by cytotoxic T-cells, and/or a humoral immune response mediated primarily by helper T-cells, which in turn activates B-cells, leading to antibody production.
  • cells of an M. hyo isolate can be inactivated using a variety of known methods, e.g., with binary ethyleneimine (BEI) as described in U.S. Patent No. 5,565,205, or with, for example, formalin, heat, beta propriolactone (BPL), irradiation or glutaraldehyde.
  • BEI binary ethyleneimine
  • BPL beta propriolactone
  • M. hyo bacterins suitable for use in present invention can also be obtained through various commercial sources. Such sources include but are not limited to: RESPIFENDTM (Fort Dodge, American Home Products), HYORESPTM (Merial Ltd), M + PACTM (Schering Plough), PROSYSTEM MTM (Intervet), INGLEVAC MTM (Boehringer), RESPISURE ® (Pfizer Inc.), RESPISURE ONETM, STELLAMUNETM Mycoplasma (Pfizer Inc.), and STELLAMUNE ONETM Mycoplasma (Pfizer Inc.).
  • RESPIFENDTM Fort Dodge, American Home Products
  • HYORESPTM Media Card
  • M + PACTM Schering Plough
  • PROSYSTEM MTM Intervet
  • INGLEVAC MTM Boehringer
  • RESPISURE ® Pfizer Inc.
  • RESPISURE ONETM STELLAMUNETM Mycoplasma
  • STELLAMUNETM Mycoplasma P
  • hyo bacterin for use in the present invention is RESPISURE ® (Pfizer Inc.), RESPISURE ONETM (Pfizer Inc.), STELLAMU N ETM Mycoplasma (Pfizer Inc.), and STELLAMUNE ONETM Mycoplasma (Pfizer Inc.).
  • a particularly preferred source of the M. hyo bacterin for use in the method of the present invention is RESPISURE ONETM (Pfizer Inc.), prepared from strain P-5722-3 (NL1 042), acquired from Purdue University, USA, which is inactivated, preferably, with BEI.
  • Immunogenic M. hyo polypeptides for use in the vaccines of the present invention can be prepared from M. hyo bacteria using techniques known in the art, and are preferably substantially pure or homogenous.
  • suitable immunogenic M. hyo polypeptides include, but are not limited to, P44 (Wise and Kim, J. Bacteriol. 169: 5546-5555, 1987), P46 (EP 0 475 185 A1 ), P50 (Wise and Kim, 1987), P65 (U.S.
  • the immunogenic fragment of a M. hyo polypeptide includes a contiguous portion of the polypeptide of at least 7 or 8, preferably, at least 25, and more preferably, at least 50 amino acids.
  • M. hyo nucleic acid molecules suitable for use in the vaccines of the present invention include, but are not limited to, nucleic acids encoding a polypeptide such as, but not limited to, P44, P46, P50, P65, P70, P97, and P102, or an immunogenic fragment of such a polypeptide.
  • the multiple-strain vaccines of the present invention include a bacterin prepared from at least one M. hyo strain, and further include immunogenic components which are prepared from another strain or other strains of M. hyo.
  • the vaccines include bacterins prepared from two or more M. hyo strains.
  • the vaccines of the present invention also include at least one immunogen prepared from a pathogen other than M. hyo.
  • pathogens include viral, bacterial or parasitic pathogens, and can be in the form of inactivated whole or partial cell preparation, a modified live form, or proteins or immunogenic fragments thereof.
  • pathogens examples include porcine reproductive and respiratory syndrome virus, pseudorabies virus, porcine circovirus type II, swine influenza virus, Salmonella cholerasuis, Salmonella typhimurium, Erysipelothrix rhusiopathiae, Lawsonia intracellulars, Haemophilus parasuis, Bordetella bronchiseptica, Streptococcus suis, Actinobacillus pleuropneumoniae, Escherichia coli, Pasteurella multocida, and Clostridium perfringens type A and type C.
  • immunogenic materials prepared from M. hyo and other pathogens can be combined with a veterinary-acceptable carrier to form a vaccine composition.
  • a veterinary-acceptable carrier includes any and all solvents, dispersion media, coatings, adjuvants, stabilizing agents, diluents, preservatives, antibacterial and antifungal agents, isotonic agents, adsorption delaying agents, and the like.
  • Diluents can include water, saline, dextrose, ethanol, glycerol, and the like.
  • Isotonic agents can include sodium chloride, dextrose, mannitol, sorbitol, and lactose, among others.
  • Stabilizers include albumin, among others.
  • Adjuvants suitable for use in accordance with the present invention include, but are not limited to, the RIBI adjuvant system (Ribi Inc.), alum, aluminum hydroxide gel, mineral gels, cholesterol, lysolecithin, pluronic polyols, polyanions, non-ionic block polymers, mineral oils, vegetable oils, oil-in- water emulsions such as AMPHIGEN ® (Hydronics, USA); water-in-oil emulsions such as, e.g., Freund's complete and incomplete adjuvants, emulsifier such as lecithin; Block co-polymer (CytRx, Atlanta GA); SAF-M (Chiron, Emeryville CA); saponins such as, e.g., Quil A, QS-21 (Cambridge Biotech Inc., Cambridge MA), GPI- 0100 (Galenica Pharmaceuticals, Inc., Birmingham, AL) or other saponin fractions; monophosphoryl lipid A; Avr
  • a preferred adjuvant for use in the vaccine compositions in accordance with the present invention is an oil-in-water emulsion adjuvant, particularly, AMPHIGEN ® (Hydronics, USA).
  • the immunogenic materials and the veterinary-acceptable carrier can be combined in any convenient and practical manner to form a vaccine composition, e.g., by admixture, solution, suspension, emulsification, encapsulation, absorption and the like, and can be made in formulations such as tablets, capsules, powder, syrup, suspensions that are suitable for injections, implantations, inhalations, ingestions or the like.
  • the pharmaceutical compositions of the present invention should be made sterile by well-known procedures.
  • immunologically effective amount refers to the amount of M. hyo immunogens in a vaccine composition that is effective to induce a protective immune response in an animal.
  • the amount of a M. hyo bacterin that is effective as an immunogen contains about 1x10 to
  • the amount of a M. hyo polypeptide or an immunogenic fragment of such polypeptide effective as an immunogen can generally be in the range of about 0.01 ⁇ g to about 200 ⁇ g per dose.
  • the amount of a nucleic acid molecule encoding a M. hyo polypeptide or an immunogenic fragment of such polypeptide effective as an immunogen can generally be in the range of about 0.01 ⁇ g to about 200 ⁇ g per dose.
  • the vaccines can be formulated such that one dose is about 0.5 to 3.0 ml, preferably about 1.5 ml to about 2.5 ml, and more preferably about 2 ml.
  • the vaccine composition can be administered to an animal for treating or preventing the animal against a disease caused by M. hyo.
  • animal refers to all non-human animals, including food animals such as cattle, sheep, and pig.
  • pig and “swine” are used herein interchangeably and refer to piglets, swine, pigs, porcine, sows, gilts, barrows, boars and members of the Suidae family.
  • treating or preventing with respect to a disease caused by M. hyo means to inhibit the replication of M. hyo bacteria, to inhibit M. hyo transmission, or to prevent M. hyo from establishing itself in the host, and/or to alleviate the symptoms of the disease.
  • the treatment is considered therapeutic if there is a reduction in bacterial load, decrease in pulmonary infections, and/or increase in food uptake and weight gain.
  • the vaccine can be administered to an animal by known routes, including the oral, intranasal, mucosal topical, transdermal, and parenteral (e.g., intravenous, intraperitoneal, intradermal, subcutaneous or intramuscular). Administration can also be achieved using needle-free delivery devices. Administration can be achieved using a combination of routes, e.g., first administration using a parental route and subsequent administration using a mucosal route. Preferred routes of administration are intranasal and intramuscular administrations.
  • the vaccine can be administered once or in multiple doses to achieve effective immunoprotection.
  • the present invention is further illustrated by, but not limited to, the following examples.
  • BEI Binaryethylenelmine
  • BEA is added to a final concentration of approximately 4.0 mM.
  • the BEA is chemically changed to BEI.
  • the culture is incubated at 37 + 2°C with constant agitation for at least 24 hours.
  • a filter sterilized aqueous solution of sodium thiosulfate is added to a final concentration of approximately 4 mM to neutralize the excess BEI.
  • the culture is incubated at 37 + 2°C with constant agitation for an additional 24 hours.
  • Fresh medium containing 0.0026% phenol red is inoculated with a 5-20% inoculum and incubated at 37 + 2°C for at least one week prior to examination for a color change, which is indicative of failure to inactivate.
  • Bulk samples are tested for sterility in thioglycollate broth at 37 + 2°C, and trypticase soy broth at room temperature. The inactivated culture may be transferred into sterile storage vessels and stored at 2-8°C until assembled.
  • Pigs approximately one week of age or older are selected for vaccination. Serological status to M. hyopneumoniae is assessed in an ELISA assay. Pigs with an ELISA value of less than 0.50 are considered M. hyopneumoniae-negalive. Pigs with an ELISA value of greater than 0.50 are considered serologically positive for M. hyopneumoniae.
  • a single vaccine comprising two or more inactivated M. hyopneumoniae whole cell preparations is used to immunize pigs. The potency of the vaccine preparations is determined prior to use by relative antigen quantitation as compared to a reference M.
  • hyopneumoniae bacterin and as determined by a solid phase immunoassay which measures the quantity of M. hyopneumoniae antigen in the vaccine.
  • the same liquid adjuvant (AMPHIGEN) used in formulating RESPISURE ® (Pfizer, Inc) is used in formulating the multivalent vaccine.
  • AMPHIGEN is used as the placebo vaccine (i.e., without bacterial cells).
  • the challenge inoculum is provided as 10 ml aliquots of lung homogenate, frozen at -70°C.
  • the inoculum is thawed, diluted in Friis Mycoplasma Broth to achieve a 1 :100 dilution, and kept on ice until administered.
  • an aliquot of the challenge inoculum is cultured to confirm the absence of bacterial contamination.
  • a second aliquot is back titrated to confirm the challenge dose.
  • Pigs are identified with ear tags while they are still on the sow.
  • the pigs are allotted to pens and treatment groups according to a generalized random block design.
  • Pigs are vaccinated with either a 2 ml intramuscular dose of M. hyopneumoniae bacterin(s) or a 2 ml intramuscular dose of placebo. If required, two to three weeks following the first vaccination, pigs receive a second dose of the appropriate vaccine. Two to four weeks following the final vaccination, each pig is sedated with the appropriate dose of a Telazol, xylazine and ketamine combination, and challenged intratracheally with approximately 10 ml_ of the 1 :100 suspension of the challenge culture. All pigs are subsequently monitored daily for signs of clinical disease.
  • pigs Approximately 4 weeks following challenge, all pigs are euthanized. Upon necropsy, pigs will be examined for the presence of injection site lesions caused by the experimental vaccines, and any untoward reactions will be recorded. Tissue samples from all injection site reactions may be obtained for histopathology and will be placed in a sufficient quantity of 10% neutral buffered formalin for future microscopic evaluation. The lungs are removed and evaluated, including an estimate of the extent of pathology associated with mycoplasmal respiratory disease. Each lung lobe is examined, and lesions are sketched to estimate the percent involvement of each lobe. The degree of gross lesions present is recorded.
  • Efficacy is evaluated based on percent of lung lesions typical of a M. hyopneumoniae infection. Pigs in a treatment group (vaccinates) are determined to have a percentage of total lung with lesions that is significantly (P ⁇ 0.05) less than pigs in the placebo group. Percent gross involvement per each lung lobe is weighted using the following ratios of individual lung lobes to total lung mass: left cranial 10%, left middle 10%, left caudal 25%; right cranial 10%, right middle 10%, right caudal 25%, and accessory 10%. The weighted lung lobe values are then summed across lobes to yield the Percentage of Total Lung with Lesions (Pointon et al., 1992).
  • Protection against challenge with virulent M. hyopneumoniae is evaluated in pigs using two doses of a multivalent M. hyopneumoniae vaccine.
  • pigs in one treatment group are vaccinated with a 2 ml intramuscular dose of the multivalent M. hyopneumoniae vaccine, while those in a second group are vaccinated intramuscularly with 2 ml of a placebo.
  • Two to three weeks following the first vaccination pigs are vaccinated with a second 2 ml intramuscular dose of the vaccine.
  • each pig is challenged intratracheally with approximately 1 O mL of the challenge suspension.
  • All pigs are subsequently monitored daily for signs of clinical disease.
  • An aliquot of the challenge material is cultured at the time of inoculation to confirm the absence of bacterial contamination, and a second aliquot is back-titrated to confirm the M. hyopneumoniae challenge dose.
  • the post-mortem examination includes an estimate of the extent of pathology associated with mycoplasmal respiratory disease. Each lung lobe is examined, and lesions are sketched to estimate the percent involvement of each lobe. The degree of gross lesions present is recorded.
  • Protection against challenge with virulent M. hyopneumoniae is evaluated in pigs using a single dose of a multivalent M. hyopneumoniae vaccine.
  • pigs in one treatment group are vaccinated with a 2 ml intramuscular dose of the M. hyopneumonia ⁇ vaccine, while those in a second group are vaccinated intramuscularly with 2 ml of a placebo.
  • each pig is challenged intratracheally with approximately 10 ml. of the challenge suspension. All pigs are subsequently monitored daily for signs of clinical disease. An aliquot of the challenge material is cultured at the time of inoculation to confirm the absence of bacterial contamination, and a second aliquot is back- titrated to confirm the M. hyopneumoniae challenge dose.
  • the post-mortem examination includes an estimate of the extent of pathology associated with mycoplasmal respiratory disease. Each lung lobe is examined, and lesions are sketched to estimate the percent involvement of each lobe. The degree of gross lesions present is recorded.

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Abstract

Cette invention concerne des vaccins multisouches à base de Mycoplasma hyopneumoniae. Cette invention porte plus particulièrement sur des vaccins préparés à partir d'au moins deux souches de Mycoplasma hyopneumoniae, sous la forme d'une bactérine constituée de cellules entières ou partielles ou sous la forme d'un vaccin fractionné. Les vaccins multisouches décrits dans cette invention sont utiles pour protéger les porcs contre des infections causées par Mycoplasma hyopneumoniae et garantissent une protection plus complète que celle des vaccins à souche unique.
PCT/IB2005/003412 2004-11-24 2005-11-11 Vaccins multisouches a base de mycoplasma hyopneumoniae WO2006056841A1 (fr)

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CN105521488A (zh) * 2015-12-26 2016-04-27 哈药集团生物疫苗有限公司 猪细小病毒病-猪伪狂犬病二联灭活疫苗及其制备方法和应用
EP3072523A1 (fr) * 2013-11-21 2016-09-28 Agricultural Technology Research Institute Composition permettant de prévenir et de soigner une infection à mycoplasme
CN106928373A (zh) * 2017-03-17 2017-07-07 青岛明勤生物科技有限公司 一种猪支原体肺炎多表位黏膜疫苗
CN110227151A (zh) * 2012-12-28 2019-09-13 勃林格殷格翰动物保健有限公司 包含支原体抗原的免疫原性组合物
CN110438029A (zh) * 2019-06-25 2019-11-12 成都天邦生物制品有限公司 一种猪肺炎支原体新型灭活方法
CN119119295A (zh) * 2024-09-10 2024-12-13 湖南农业大学 一种猪肺炎支原体融合蛋白及其制备方法和应用

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EP3072523A4 (fr) * 2013-11-21 2017-05-03 Agricultural Technology Research Institute Composition permettant de prévenir et de soigner une infection à mycoplasme
CN110302368A (zh) * 2013-11-21 2019-10-08 财团法人农业科技研究院 防治霉浆菌感染的组合物
CN110302368B (zh) * 2013-11-21 2022-11-04 财团法人农业科技研究院 防治猪霉浆菌感染的组合物
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CN119119295A (zh) * 2024-09-10 2024-12-13 湖南农业大学 一种猪肺炎支原体融合蛋白及其制备方法和应用

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