WO1995012411A1 - Vaccin et procede de traitement contre les infections a chlamydia - Google Patents

Vaccin et procede de traitement contre les infections a chlamydia Download PDF

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Publication number
WO1995012411A1
WO1995012411A1 PCT/US1994/012626 US9412626W WO9512411A1 WO 1995012411 A1 WO1995012411 A1 WO 1995012411A1 US 9412626 W US9412626 W US 9412626W WO 9512411 A1 WO9512411 A1 WO 9512411A1
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Prior art keywords
momp
vaccine
preparation
chlamydia
ebs
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PCT/US1994/012626
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English (en)
Inventor
Marta Iris Sabara
James Evan Sandbulte
Julie Ann Terwee
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Pfizer Inc.
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Publication date
Application filed by Pfizer Inc. filed Critical Pfizer Inc.
Priority to AU11297/95A priority Critical patent/AU701247B2/en
Priority to BR9407986A priority patent/BR9407986A/pt
Priority to NZ276874A priority patent/NZ276874A/en
Priority to EP95902425A priority patent/EP0726775A4/fr
Publication of WO1995012411A1 publication Critical patent/WO1995012411A1/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
    • A61K39/118—Chlamydiaceae, e.g. Chlamydia trachomatis or Chlamydia psittaci

Definitions

  • Chlamydia trachomatis is the most prevalently sexually transmitted bacterial pathogen in the United States today.
  • the complications resulting from chlamydial infections can be quite serious. Those infected may suffer from pelvic inflammatory disease, urethritis, urethral syndrome and urinary tract infections. It has also been confirmed that infection may result in spontaneous abortion in pregnant woman.
  • chlamydial conjunctivitis and chlamydial pneumonia may occur in infants infected from their mothers as they pass through the birth canal.
  • Chlamydial infections in animals and humans are quite similar.
  • the organism C. psittaci in animals primarily affects the mucosal epithelial cells of the eye and genital tract. After infection, a chronic carrier state typically develops with symptoms reoccurring during stress.
  • Asymptomatic female animals carrying C. psittaci in epithelial cells of the distal genital tract have been shown to infect their newborn during parturition.
  • Chlamydial infection in sheep is an economically devastating disease in many countries.
  • Ovine chlamydial abortion also referred to as ovine enzootic abortion (OEA) results from infection by the C. psittaci pathogen. This organism causes a necrotizing placentitis in sheep and consequent abortion of the lamb.
  • This vaccine and similar products have been used successfully for decades in sheep to protect against OEA strains of the pathogen. Recently, however, the efficacy of this vaccine has been quite variable, with outbreaks of chlamydial OEA infection occurring in vaccinated flocks. Heterologous challenge experiments have indicated possible strain variation to be the cause.
  • Tan et al. used a modified procedure for isolating chlamydial outer membrane complexes (COMCs) to produce a subcellular vaccine highly enriched in undenatured MOMP. This preparation, given as a single dose containing 20 ⁇ g of protein, protected sheep against OEA. A single dose of a vaccine prepared from purified EBs, which contained 160 ⁇ g protein, also provided protection against OEA in sheep. Tan et al.
  • MOMP as the major protective component in OEA vaccines and suggested using a recombinant DNA approach to protect against OEA because they believed a 40 kDa MOMP antigen alone was sufficient. While the vaccine disclosed by Tan et al. contained residual amounts of lipopolysaccharide (LPS), this component was not considered important in development of a ⁇ vaccine against OEA chlamydial infections because serum containing antibodies against LPS did not confer protection in passive transfer experiments, and the complement-fixing antibodies thought to be directed against genus-specific epitopes of LPS did not correlate with protection against ovine abortion strains of C. psittaci.
  • LPS lipopolysaccharide
  • the present invention provides a vaccine for treatment of chlamydial infections comprising major outer membrane protein and lipopolysaccharide from a Chlamydia organism.
  • the present invention provides a method for treatment of chlamydial infections comprising administering to an infected animal an effective amount of a vaccine comprising major outer membrane protein and lipopolysaccharide from a Chlamydia organism.
  • the present invention provides a method for immunizing a healthy animal against chlamydial infections comprising administering to a healthy animal a vaccine comprising major outer membrane protein and lipopolysaccharide from a Chlamydia organism.
  • the present invention provides a vaccine for treatment and immunization against chlamydial infections in animals.
  • the vaccine is comprised of major outer membrane protein (MOMP) either alone in purified form or in the context of elementary bodies (EBs) or outer membrane complexes (COMCs), with lipopolysaccharide (LPS) from a Chlamydia organism, wherein the Chlamydia organism is preferably C. psittaci or C. trachomatis, more preferably C. psittaci of the Baker strain.
  • MOMP major outer membrane protein
  • EBs elementary bodies
  • COMPs outer membrane complexes
  • LPS lipopolysaccharide
  • the effect of the vaccine may be enhanced by addition of an adjuvant.
  • MOMP in the vaccine is provided in purified form or in the context of EBs or COMCs.
  • MOMP can be purified by various methods including but not limited to chromatographically or electrophoretically.
  • Electrophoretic purification of MOMP is accomplished in the following manner. Chlamydia harvest fluid is centrifuged, and the resulting pellet is resuspended in water. Samples are then resolved by gel electrophoresis, preferably sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Proteins in the samples are solubilized, preferably by heating at about 95°C for approximately 5 minutes in buffer, preferably Tris buffer, pH 6.8, containing SDS, 2-mercaptoethanol, glycerol, and bromophenol blue. Electrophoresis is carried out using polyacrylamide gels. The gels are stained, then briefly destained. The 40 kDa band is then excised, placed in a dialysis bag, and the protein is electroeluted out of the gel.
  • SDS-PAGE sodium dodecyl sulphate polyacrylamide gel electrophoresis
  • Non-MOMP proteins are extracted from EBs, preferably by treatment with N-lauroyl-sarcosine in phosphate buffered saline (PBS) containing EDTA for 1 hour at 37 °C. Following extraction, the solution is centrifuged. The resulting pellet is washed and resuspended in buffer, preferably sodium phosphate buffer containing MgCl, deoxyribonuclease and ribonuclease A. The suspension is then incubated at about 37 °C for approximately 2 hours and spun.
  • PBS phosphate buffered saline
  • the resulting pellet is washed and resuspended in buffer, preferably PBS containing sodium dodecyl sulfate and EDTA.
  • buffer preferably PBS containing sodium dodecyl sulfate and EDTA.
  • the suspension is incubated again at about 37°C and then spun.
  • the resulting supernatant is dialyzed against buffer, preferably sodium phosphate buffer, containing dithiothreitol and SDS, then loaded onto a hydroxylapatite column previously equilibrated with the same buffer.
  • the column is washed and a linear gradient from about 0.1 to about 0.6 M sodium phosphate, pH 6.4, containing dithiothreitol and SDS is run.
  • the pellet from the SDS extraction is re-extracted. Fractions from the supernatant and the pellet containing MOMP are pooled and then dialyzed against water.
  • the MOMP preparation in the vaccine can also be provided in the context of
  • the EB subtraction preparation is isolated from Chlamydia harvest fluid.
  • Chlamydia organisms preferably Chlamydia psittaci, more preferably Baker strain, is propagated in mammalian cells.
  • the harvest fluid from the cells is concentrated, layered on top of 35% Renografin-76, and centrifuged.
  • the pellet is resuspended, layered on top of a discontinuous gradient of diatrizoate meglunione and diatrizoate sodium and centrifuged.
  • the band at the 44-52% interface which contains the EBs is collected, washed and resuspended in buffer, preferably a phosphate buffer, more preferably 0.01 M phosphate buffer, pH 8.0, containing 0.15 M NaCl (PBS).
  • buffer preferably a phosphate buffer, more preferably 0.01 M phosphate buffer, pH 8.0, containing 0.15 M NaCl (PBS).
  • the EBs are then inactivated, preferably with binary ethylenimine (BEI), ⁇ - propiolactone, formalin or glutaraldehyde. If BEI is used in inactivation the solution must be neutralized, preferably by addition of sodium thiosulfate.
  • the inactivated EBs are centrifuged and the resulting pellet is solubilized, preferably using PBS containing N-lauroyl- sarcosine and EDTA. The solution is then centrifuged, the resulting pellet being washed and resuspended in PBS.
  • Lipopolysaccharide is also added to the vaccine.
  • LPS is isolated via electrophoresis.
  • Samples of the harvest fluid pellet are prepared for electrophoresis as described for the MOMP-E.
  • Electrophoresis is carried out on polyacrylamide gels. It is preferred to use either a Tris/tricine buffer system or a Tris/glycine buffer system with interior resolution.
  • the portion of the gel below the 6 kDa marker is cut off and placed in a basic solution, preferably 0.1 M glycine-NaOH, pH 11.0 and incubated. The liquid is separated from the gel, the pH is adjusted to neutrality and then dialyzed.
  • MOMP-C, MOMP-E, EBs, COMCs and LPS are placed in vials and lyophilized. The amount of LPS is determined by weighing the lyophilized samples.
  • Nials are rehydrated with a pharmaceutically acceptable carrier. Such carriers include normal isotonic saline, standard 5% dextrose in water or water, preferably adjuvanted. Examples of adjuvants include, but are not limited to, Quil A, Alhydrogel, and Quil A and 5% Alhydrogel in tissue culture media. Vials containing LPS are rehydrated first. These solutions are then used to rehydrate the MOMP preparations resulting in a vaccine containing both the MOMP preparation and the LPS preparation.
  • the vaccine is administered to an animal suffering from a Chlamydial infection.
  • the vaccine is also administered to healthy animals as immunization against infection by a Chlamydia organism.
  • the vaccine can be administered subcutaneously, intramuscularly, intraperitoneally, intravitreally, orally, intranasally or by suppository at doses ranging from 0.01-100 ⁇ g/dose of MOMP and LPS each.
  • MOMP preparation refers to any vaccine preparation having purified MOMP, including, but not limited to, MOMP-E and MOMP-C, and MOMP in the context of EBs or COMCs.
  • LPS preparation refers to a vaccine preparation having purified lipopolysaccharide.
  • Effective amount refers to that amount of vaccine which invokes in an animal infected by a Chlamydia organism an immune response sufficient to kill the organism.
  • adjuvant refers to materials which when injected on their own produce a state of nonspecific immunity expressed as a heightened resistance to infection. An example is Quil A in 5% Alhydrogel in tissue culture media.
  • Example 1 Subfraction Antigen Preparations Chlamydia harvest fluid. Chlamydia psittaci, Baker strain was propagated in dog kidney (DK) cells in DMEM with 2% fetal bovine serum. The harvest fluid was inactivated with 1% BEI and the solution neutralized by addition of 0.25% sodium thiosulfate.
  • Chlamydia elementary bodies ⁇ on-inactivated Chlamydia harvest fluid was concentrated using a stirred cell concentrator or by centrifugation. The concentrate or pellet was layered on top of 35% Renografin-76 (Squibb Diagnostics, New Brunswick, NJ 08903), and centrifuged at 43,000 g for 1 hour. The pellet was resuspended and layered on top of a discontinuous gradient of 40, 44 and 52% Renograf ⁇ n-76 (Squibb Diagnostics, New Brunswick, NJ 08903) and centrifuged at 43,000 g for 1 hour.
  • the band at the 44-52% interface containing the EBs was collected, washed and resuspended in 0.01 M phosphate buffer, pH 8.0, containing 0.15 M NaCl (PBS).
  • the EBs were inactivated with 1% BEI and the solution neutralized by addition of 0.25% sodium thiosulfate.
  • Chlamydia outer membrane complexes (COMCs). Inactivated EBs were centrifuged at 100,000 g for 1 hour at 10°C, and the resulting pellets solubilized with PBS containing 2% N-lauroyl-sarcosine and 1.5 mM EDTA for 1 hour, at 37°C. The solution was subjected to centrifugation at 100,000 g for 1 hour and the pellet washed once in PBS and then resuspended in PBS.
  • COCs Chlamydia outer membrane complexes
  • MOMP-C Chromatographically purified MOMP
  • the MOMP was chromatographically purified using a modification of the method described by Caldwell et al. (1981) Infect. Immun., 31:1161-1176. Briefly, EBs prepared as above were treated with 2% N-lauroyl-sarcosine in PBS containing 1.5 mM EDTA for 1 hour at 37°C to extract non-MOMP proteins from the outer membrane complex.
  • the solution was centrifuged at 100,000 g for 1 hour, and the resulting pellet was washed in PBS then resuspended in 3-5 ml of 0.02 M sodium phosphate containing 10 mM MgC12 and 25 ⁇ g each of deoxyribonuclease I and ribonuclease A. This suspension was incubated at 37 °C for 2 hours then centrifuged at 100,000 g for 1 hour. The pellet was washed in PBS, then resuspended in 2% sodium dodecyl sulfate (SDS) in PBS with 1.5 mM EDTA and incubated for 1 hour at 37°C. The suspension was centrifuged at 100,000 g for 1 hour.
  • SDS sodium dodecyl sulfate
  • the resulting supernatant was dialyzed again 0.01 M sodium phosphate, pH 6.4, containing 1 mM dithiotreitol and 0.1% SDS (start buffer) and loaded onto a hydroxylapatite column which had been equilibrated in start buffer. The column was washed with start buffer, and then a 150 ml linear gradient of 0.1 to 0.6 M sodium phosphate, pH 6.4, containing 1 mM dithiotreitol and 0.1% SDS was initiated and 1 ml fractions were collected.
  • the pellet from the SDS extraction was re-extracted for 30 minutes each at 37 °C with periodic sonication sequentially using each of the following buffers: 1% N-lauroyl- sarcosine in 0.01 M sodium phosphate, pH 7.4; 1% N-lauroyl-sarcosine and 10 mM dithiotreitol in 0.01 M sodium phosphate, pH 7.4; and 1% octylglucoside and 10 mM dithiotreitol in 0.01 M sodium phosphate, pH 7.4 according to the method of Bavoil et al. (1984) Infect. Immuno., 44:479-485.
  • MOMP-E Electrophoretically purified MOMP
  • Proteins were solubilized by heating at 95 ⁇ C for 5 minutes in a buffer containing 2% (w/v) SDS, 5% 2-mercaptoethanol (v/v), 3% (w/v) glycerol, 0.002% (w/v) bromophenol blue, and 50 mM Tris (pH 6.8). Electrophoresis was carried out using 10% (w/v) polyacrylamide gels (1.5 mm thick) in the discontinuous buffer system of Laemmli (1970) Nature (London), 227:680-685. The gels were stained with Coomassie Blue G in 50% methanol and 10% acetic acid, and briefly destained in 50% methanol and 10% acetic acid.
  • the 40 kDa band was then excised, placed in a 12-14 kDa molecular weight cut-off dialysis bag and the protein electroeluted out of the gel for 1 hour at 50 V.
  • Lipopolysaccharide (LPS) Lipopolysaccharide
  • Samples of the harvest fluid pellet were prepared for electrophoresis as described for the MOMP-E. Electrophoresis was carried out on 12.5% polyacrylamide gels using the Tris/tricine buffer system of Schagger and von Jagow (1987) Anal. Biochem. 166:368-379, wherein the cathode buffer was 0.1 M Tris, 0.1M Tricine, 0.1% SDS, pH 8.25 and the anode buffer was 0.2M Tris, pH 8.9.
  • the portion of the gel below the 6 kDa marker was cut off and placed in a solution of 0.1 M glycine-NaOH, pH 11.0 and incubated at 37°C for 3 hours. The liquid was then removed from the gel, the pH adjusted to neutrality and then dialyzed against distilled water using 1 kDa molecular weight cut-off dialysis membrane.
  • Example 3 Quantitation and Evaluation of Protein and LPS Protein was quantitated using a BCA assay kit (Pierce, P.O. Box 1A,
  • the membranes were then blocked with 5% instant non-fat dry milk in PBS followed by incubation with the specific antibody for 1 hour at room temperature. Blots were then washed in PBS containing 0.3% Tween (v/v) and incubated with goat anti-cat alkaline phosphatase-labeled antibody (Kirkegaard & Perry Laboratories Inc., 2 Cessna Court, Gaithesburg, Maryland 20879). After extensive washing of the membranes, color was developed using BCIP/NBT substrate (Kirkegaard & Perry Laboratories Inc., 2 Cessna Court, Gaithesburg, Maryland 20879). Stained gels and blots were analyzed by optical image scanning using the Bio Image System (Millipore Corporation, Bedford, MA 01730).
  • Subfraction antigen preparation for studies I-III were formulated as follows for vaccination of mice.
  • study I a specific lot of unprocessed infected tissue culture fluid was used as a positive control since previous studies demonstrated its efficacy.
  • the quantity of EBs in the vaccine was determined by standardizing to the western blot intensity of the MOMP band in the harvest fluid. Based on this, the protein concentration in the EB vaccine was 0.575 ⁇ g/100 ⁇ l. Three 10-fold serial dilutions of both harvest fluid and EB vaccines were also made.
  • EBs and COMCs were formulated as follows.
  • the quantity of COMCs in the vaccine was determined by standardizing to the western blot intensity of the MOMP band in a purified EB preparation.
  • the purified EB preparation was then diluted in PBS to equal the MOMP concentration in COMCs.
  • These were then further diluted in adjuvant (2.5 ⁇ g/ml Quil A) in 0.85% NaCl to a total protein concentration of 5 ⁇ g/100 ⁇ l.
  • adjuvant 2.5 ⁇ g/ml Quil A
  • the same procedure was followed to produce the COMC vaccine resulting in a protein concentration of 2.8 ug/100 ⁇ l and 0.28 ⁇ g/100 ⁇ l.
  • mice Female Swiss White CF-1 mice weighing 12-14 grams (Charles River) received 2 vaccinations of 100 ⁇ l subcutaneously, two weeks apart. There were 8 mice in each group with the exception of the 10 ⁇ g group for the MOMP-C, MOMP-E, LPS, MOMP-E+LPS groups, the 0.058 ⁇ g group for the EB and the 0.81 xg group for the harvest fluid in which there were 10 mice per group. The 2 additional mice in these groups were sacrificed and bled on the day the remainder of the mice were challenged. Vaccinates as well as 10 controls were challenged with an intraperitoneal inoculation of C. psittaci, Cello strain (Cello (1967) Am. J. Ophthalmol., 63:1270-1273) 2 weeks after the second immunization.
  • mice were challenged with 10-fold serial dilutions of the challenge material to confirm the LD50.
  • All the control mice (10 per group) died. All subunit preparations, except LPS, protected 100% of the mice when administered at 100 ⁇ g/dose.
  • a dose-related titration of the protective effect was also observed.
  • Comparison of the various MOMP-containing preparations administered at the 10 ⁇ g dose indicated that both MOMP-C alone and MOMP-E plus LPS still protected 100% of the mice, while MOMP-E could only induce a 60% protective level. Comparable levels of protection were also observed with the 1.0 ⁇ g and 0.1 ⁇ g doses of the MOMP-C alone and MOMP-E plus LPS preparations. These levels were significantly greater than that induced by MOMP-E alone. See data provided in Table 1.
  • EBs were fixed with methanol to 96- well round-bottom Immulonb 2 plates (Dynatech Laboratories, 14340 Sullyfield Circle, Chantilly, Virginia) at 1 ⁇ g/well. Plates were washed with distilled water, then blocked with 3% horse serum (Hy- Clone Laboratories, Inc., 1725 South HyClone Road, Logan, Utah 84321) in PBS for 1 hour at room temperature. Mouse sera was diluted in PBS containing 0.3% Tween (v/v) and applied to plates.
  • Serum titers were determined for two randomly chosen mice from each dose group prior to being challenged. A correlation between the ability of the vaccines to protect mice from infection and the EB -specific serum response was observed. Western blot analysis from mice vaccinated with MOMP-C alone and MOMP-E plus LPS indicated that the response was almost exclusively directed to the MOMP.

Abstract

Vaccin destiné au traitement des infections à chlamydia, constitué d'une préparation de protéine de membrane externe majeure (MOMP) et d'une préparation de lipopolysaccharide (LPS) obtenue à partir d'un organisme porteur de chlamydia. Procédé de traitement et d'immunisation des animaux contre les infections à chlamydia.
PCT/US1994/012626 1993-11-03 1994-11-02 Vaccin et procede de traitement contre les infections a chlamydia WO1995012411A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
AU11297/95A AU701247B2 (en) 1993-11-03 1994-11-02 Vaccine and method for treatment of chlamydial infections
BR9407986A BR9407986A (pt) 1993-11-03 1994-11-02 Vacina e método para tratamento de infecçoes clamídicas
NZ276874A NZ276874A (en) 1993-11-03 1994-11-02 Vaccine for treating chlamydia comprising a major outer membrane protein and lipopolysaccharide preparation from a chlamydia organism
EP95902425A EP0726775A4 (fr) 1993-11-03 1994-11-02 Vaccin et procede de traitement contre les infections a chlamydia

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14763693A 1993-11-03 1993-11-03
US08/147,636 1993-11-03

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WO1995012411A1 true WO1995012411A1 (fr) 1995-05-11

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EP (1) EP0726775A4 (fr)
CN (1) CN1134112A (fr)
AU (1) AU701247B2 (fr)
BR (1) BR9407986A (fr)
CA (1) CA2175081A1 (fr)
NZ (1) NZ276874A (fr)
WO (1) WO1995012411A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997041889A1 (fr) * 1996-05-06 1997-11-13 Bayer Corporation Vaccins pour felins contenant une chlamydia psittaci et leur procede de production
WO2000006743A2 (fr) * 1998-07-27 2000-02-10 Connaught Laboratories Limited Antigenes de chlamydia et fragments d'adn correspondants, et utilisations de ceux-ci
WO2001046226A2 (fr) * 1999-12-22 2001-06-28 Aventis Pasteur Limited Antigenes de chlamydia, fragments d'adn correspondants et utilisations de ceux-ci
WO2001046224A2 (fr) * 1999-12-22 2001-06-28 Aventis Pasteur Limited Antigenes anti-chlamydia, fragments d'adn correspondants et leurs utilisations
WO2001046225A2 (fr) * 1999-12-22 2001-06-28 Aventis Pasteur Limited Antigenes anti-chlamydia, fragments d'adn correspondants et leurs utilisations
WO2003049762A2 (fr) * 2001-12-12 2003-06-19 Chiron Srl. Immunisation contre chlamydia trachomatis
US6676949B2 (en) * 1998-12-04 2004-01-13 University Of Manitoba Two-step immunization procedure against Chlamydia infection
US7459524B1 (en) 1997-10-02 2008-12-02 Emergent Product Development Gaithersburg Inc. Chlamydia protein, sequence and uses thereof
US7482020B2 (en) * 1995-09-21 2009-01-27 Hennessy Kristina J Process for making an adjuvanted vaccine comprising host albumin
US8735543B2 (en) 2010-05-28 2014-05-27 Spixia Biotechnology Ab Chimeric MOMP antigen
CN108367058A (zh) * 2015-11-10 2018-08-03 俄亥俄州创新基金会 与加快的体液亲和力相关的方法和组合物
US11253582B2 (en) 2015-02-10 2022-02-22 Ohio State Innovation Foundation Chlamydia-activated B cell platforms and methods thereof

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BUCK et al., "American Type Culture Collection Catalogue of Animal Viruses and Antisera, Chlamydia and Rickettsiae", 6th edition, published 1990, by AMERICAN TYPE CULTURE COLLECTION (ROCKVILLE, MD), pages 171-174. *
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INFECTION AND IMMUNITY, Volume 58, Number 9, issued September 1990, TAN et al., "Protection of Sheep Against Chlamydia Psittachi Infection with a Subcellular Vaccine Containing the Major Outer Membrane Protein", pages 3101-3108. *
See also references of EP0726775A4 *
THE JOURNAL OF IMMUNOLOGY, Volume 114, Number 2, Part 2, issued February 1975, SKIDMORE et al., "Immunologic Properties of Bacterial Lipopolysaccharides (LPS): Correlation Between the Mitogenic, Adjuvant, and Immunogenic Activities", pages 770-775. *

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US7482020B2 (en) * 1995-09-21 2009-01-27 Hennessy Kristina J Process for making an adjuvanted vaccine comprising host albumin
US5972350A (en) * 1996-05-06 1999-10-26 Bayer Corporation Feline vaccines containing Chlamydia psittaci and method for making the same
WO1997041889A1 (fr) * 1996-05-06 1997-11-13 Bayer Corporation Vaccins pour felins contenant une chlamydia psittaci et leur procede de production
CZ297848B6 (cs) * 1996-05-06 2007-04-11 Bayer Corporation Deaktivovaná, imunogenicky úcinná a nereaktivní vakcína Chlamydia psittaci a zpusob její prípravy
US7655246B2 (en) 1997-10-02 2010-02-02 Emergent Product Development Gaithersburg Inc. Chlamydia protein, gene sequence and uses thereof
US7459524B1 (en) 1997-10-02 2008-12-02 Emergent Product Development Gaithersburg Inc. Chlamydia protein, sequence and uses thereof
US7534445B2 (en) 1997-10-02 2009-05-19 Emergent Product Development Gaithersburg Inc. Chlamydia protein, sequence and uses thereof
WO2000006743A2 (fr) * 1998-07-27 2000-02-10 Connaught Laboratories Limited Antigenes de chlamydia et fragments d'adn correspondants, et utilisations de ceux-ci
WO2000006743A3 (fr) * 1998-07-27 2000-05-04 Connaught Lab Antigenes de chlamydia et fragments d'adn correspondants, et utilisations de ceux-ci
US6676949B2 (en) * 1998-12-04 2004-01-13 University Of Manitoba Two-step immunization procedure against Chlamydia infection
WO2001046226A2 (fr) * 1999-12-22 2001-06-28 Aventis Pasteur Limited Antigenes de chlamydia, fragments d'adn correspondants et utilisations de ceux-ci
WO2001046226A3 (fr) * 1999-12-22 2002-04-18 Aventis Pasteur Antigenes de chlamydia, fragments d'adn correspondants et utilisations de ceux-ci
WO2001046225A3 (fr) * 1999-12-22 2001-12-06 Aventis Pasteur Antigenes anti-chlamydia, fragments d'adn correspondants et leurs utilisations
AU784193B2 (en) * 1999-12-22 2006-02-16 Sanofi Pasteur Limited Chlamydia antigens and corresponding DNA fragments and uses thereof
US7019125B2 (en) 1999-12-22 2006-03-28 Sanofi Pasteur Limited Chlamydia antigens and corresponding DNA fragments and uses thereof
WO2001046224A3 (fr) * 1999-12-22 2001-12-06 Aventis Pasteur Antigenes anti-chlamydia, fragments d'adn correspondants et leurs utilisations
WO2001046225A2 (fr) * 1999-12-22 2001-06-28 Aventis Pasteur Limited Antigenes anti-chlamydia, fragments d'adn correspondants et leurs utilisations
WO2001046224A2 (fr) * 1999-12-22 2001-06-28 Aventis Pasteur Limited Antigenes anti-chlamydia, fragments d'adn correspondants et leurs utilisations
US7361353B2 (en) 2001-12-12 2008-04-22 Novartis Vaccines And Diagnostics, Inc. Immunisation against Chlamydia trachomatis
EP2335723A1 (fr) * 2001-12-12 2011-06-22 Novartis Vaccines and Diagnostics S.r.l. Immunisation contre la Chlamydia trachomatis
WO2003049762A2 (fr) * 2001-12-12 2003-06-19 Chiron Srl. Immunisation contre chlamydia trachomatis
EP2168596A2 (fr) * 2001-12-12 2010-03-31 Novartis Vaccines and Diagnostics S.r.l. Immunisation contre la chlamydia trachomatis
EP2168596A3 (fr) * 2001-12-12 2010-07-28 Novartis Vaccines and Diagnostics S.r.l. Immunisation contre la chlamydia trachomatis
US7842297B2 (en) 2001-12-12 2010-11-30 Novartis Vaccines And Diagnostics Srl Immunisation against chlamydia trachomatis
EP2335724A1 (fr) * 2001-12-12 2011-06-22 Novartis Vaccines and Diagnostics S.r.l. Immunisation contre la Chlamydia trachomatis
WO2003049762A3 (fr) * 2001-12-12 2004-05-13 Chiron Srl Immunisation contre chlamydia trachomatis
US8735543B2 (en) 2010-05-28 2014-05-27 Spixia Biotechnology Ab Chimeric MOMP antigen
US11253582B2 (en) 2015-02-10 2022-02-22 Ohio State Innovation Foundation Chlamydia-activated B cell platforms and methods thereof
CN108367058A (zh) * 2015-11-10 2018-08-03 俄亥俄州创新基金会 与加快的体液亲和力相关的方法和组合物
JP2018532813A (ja) * 2015-11-10 2018-11-08 オハイオ・ステート・イノヴェーション・ファウンデーション 体液性親和性の加速に関する方法及び組成物
EP3373961A4 (fr) * 2015-11-10 2019-07-31 Ohio State Innovation Foundation Méthodes et compositions associées à une affinité humorale accélérée
US10835601B2 (en) 2015-11-10 2020-11-17 Ohio State Innovation Foundation Methods and compositions related to accelerated humoral affinity

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CN1134112A (zh) 1996-10-23
BR9407986A (pt) 1996-12-03
CA2175081A1 (fr) 1995-05-11
AU1129795A (en) 1995-05-23
EP0726775A4 (fr) 1999-03-31
EP0726775A1 (fr) 1996-08-21
NZ276874A (en) 1997-11-24
AU701247B2 (en) 1999-01-21

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