EP1622641A2 - Vacciner contre des maladies infectieuses utilisant des proteosomes - Google Patents

Vacciner contre des maladies infectieuses utilisant des proteosomes

Info

Publication number
EP1622641A2
EP1622641A2 EP04760725A EP04760725A EP1622641A2 EP 1622641 A2 EP1622641 A2 EP 1622641A2 EP 04760725 A EP04760725 A EP 04760725A EP 04760725 A EP04760725 A EP 04760725A EP 1622641 A2 EP1622641 A2 EP 1622641A2
Authority
EP
European Patent Office
Prior art keywords
antigen
proteosomes
immunogenic composition
liposaccharide
immune response
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP04760725A
Other languages
German (de)
English (en)
Inventor
David Hugh Jones
David S. Burt
George H. Lowell
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
ID Biomedical Corp of Quebec
Original Assignee
ID Biomedical Corp of Quebec
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by ID Biomedical Corp of Quebec filed Critical ID Biomedical Corp of Quebec
Publication of EP1622641A2 publication Critical patent/EP1622641A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • 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
    • 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
    • A61K39/07—Bacillus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • 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
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031—Proteins
    • A61K2039/6068—Other bacterial proteins, e.g. OMP
    • 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
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6087—Polysaccharides; Lipopolysaccharides [LPS]

Definitions

  • any of the aforementioned immunogenic compositions have a liposaccharide final content by weight as a percentage of Proteosome protein ranges from about 1% to about 500% in the immunogenic composition.
  • the Proteosomes and liposaccharide are obtained from the same bacteria or from different bacteria, such as Gram-negative bacteria.
  • the liposaccharide is from Gram-negative bacteria selected from Shigella species, Chlamydia species, Yersinia species, Pseudomonas species, Plesiomonas species, Escherichia species, Salmonella species, or a combination thereof.
  • the Proteosomes are from Neisseria species.
  • the immunogenic compositions of this disclosure have Proteosomes are from Neisseria meningitides and the liposaccharide is from Shigella flexneri.
  • any of the aforementioned immunogenic compositions have a ratio of Proteosomes to antigen that ranges from about 5: 1 to about 1 :500, or the ratio is at least 1:2, 1:5, or 1:10.
  • any of the aforementioned immunogenic compositions further comprise a pharmaceutically acceptable carrier, excipient or diluent.
  • Figure 6 shows the amounts of IFN- ⁇ , TNF- ⁇ and IL-5 released from splenocytes stimulated in vitro with antigen Fl-V.
  • Splenocytes were harvested from mice immunized intranasally with 50 ⁇ g of Fl-V with or without 1 ⁇ g Protollin, or injected intramuscularly with 20 ⁇ g of Fl-V adsorbed onto Alhydrogel , on day 35 after immunization.
  • FIGs 8 A and 8B show results of anthrax neutralization assays using serum and lung lavage fluid from mice immunized with rPA admixed with Protollin.
  • Figure 9 shows serum IgG in mice immunized (on days 1, 21 and 31) with 15 ⁇ g of recombinant filamentous hemagglutinin (rFHA) from Bordetella pertusis admixed with liposome (intranasally, i.n.), Protollin (i.n.), or Alhydrogel
  • rFHA recombinant filamentous hemagglutinin
  • mice were immunized i.p. with QuadracelTM
  • LPS lipopolysaccharide or lipooligosaccharide
  • Gram- negative bacteria such as Shigella flexneri or Plesiomonas shigelloides, or other Gram- negative bacteria (including Alcaligenes, Bacteroides, Bordetella, Borrellia, Brucella, Campylobacter, Chlamydia, Citrobacter, Edwardsiella, Ehrlicha, Enterobacter, Escherichia, Francisella, Fusobacterium, Gardnerella, Hemophillus, Helicobacter, Klebsiella, Legionella, Leptospira (including Leptospira interrogans), Moraxella, Morganella, Neiserria, Pasteurella, Proteus, Providencia, other Plesiomonas, Porphyromonas (including Porphyromonas (including Porphy
  • Specific or Acquired or Adaptive immune response refers to a resistance mediated by a mammalian immune system resulting from previous exposure to an infectious agent or antigen.
  • specific immunity can be a result of a naturally acquired (patent or latent) infection or from an intentional vaccination.
  • specific immunity may be passively and transitorily acquired from the transfer of antibodies from another naturally (e.g., maternally inherited), or from transfer of antibodies or immune cells by intentional inoculation (e.g., antibody mediated immunotherapy).
  • PROTEOSOME-BASED VACCINE ADJUVANTS - ("PROJUVANT” AND “PROTOLLIN")
  • virosomes liposomes with and without Lipid A, Detox (Ribi/Corixa), MF59, or other oil and water emulsions type adjuvants, such as nanoemulsions (see, e.g., U.S. Patent No. 5,716,637) or submicron emulsions (see, e.g., U.S. Patent No. 5,961,970), and Freund's complete and incomplete adjuvant.
  • a particularly preferred adjuvant is a Proteosome or Protollin.
  • the antigens are preferably from clinically relevant microorganisms, such as bacteria, viruses (e.g., Influenza, Measles, Coronavirus), parasites (e.g., Trypansome, Plasmodium, Leishmania, pathogenic bacteria) fungi (e.g., Aspergillus, Candida, Coccidioides, Cryptococcus), and the like.
  • viruses e.g., Influenza, Measles, Coronavirus
  • parasites e.g., Trypansome, Plasmodium, Leishmania, pathogenic bacteria
  • fungi e.g., Aspergillus, Candida, Coccidioides, Cryptococcus
  • SEB is known to cause illness if inhaled and maybe the cause of food poisoning.
  • the immune system of SEB intoxicated individuals is compromised and although not frequently associated with death, there is significant and wide spread incapacitating illness, such as high fever, chills, headache, muscle aches, inflammation of the lining of the eyelids, nausea, vomiting and diarrhea.
  • One or more of he polypeptides encoded by vaccinia virus ORFs with 90% sequence identity to variola virus encoded polypeptides is assumed to mediate the immune response responsible for protection following vaccinia virus immunization.
  • ORFs are known to encode extracellular virus-specific polypeptides that may be involved in eliciting a protective immune response.
  • the present invention provides a method for treating or preventing a small pox infection, comprising administering to a subject in need thereof a therapeutically effective amount of an immunogenic composition, wherein said immunogenic composition comprises Proteosomes, liposaccharide and one or more small pox antigens or a small pox viral particle extract, wherein the small pox infection is treated or prevented.
  • Ricin poisoning if unchecked, develops within several days into severe dehydration and a decrease in blood pressure resulting in death within 3-5 days after ingestion (or inhalation).
  • Ricin is a potent toxin that is fairly easily produced and can cause poisoning (toxicity) by inhalation as a small particle or following ingestion.
  • Ricin is also quite stable.
  • Symptoms of ricin poisoning include weakness, fever, cough and pulmonary edema followed by severe respiratory distress and death from hypoxemia.
  • the histopathology of aerosol exposure is characterized by necrotizing airway lesions causing tracheitis, bronchitis and interstitial pneumonia with perivascular and aleveolar edema.
  • Botulism is caused by intoxication with any of the seven distinct neurotoxins produced by the bacillus, Clostridium botulinum.
  • the botulinum toxins are proteins with molecular mass of approximately 150,000 KDa, which bind to the presynaptic membrane of neurons at peripheral cholinergic synapses to prevent release of acetylcholine and block neurotransmission.
  • the blockade is most evident clinically in the cholinergic autonomic nervous system and at the neuromuscular junction. Symptoms of inhalation botulism may begin as early as 24-36 hours following exposure or as late as several days. Initial signs and symptoms include ptosis, generalized weakness, lassitude, and dizziness. Development of respiratory failure may be abrupt.
  • the present invention provides a method for eliciting an immune response against botulinum toxin, comprising administering to a subject in need thereof a therapeutically effective amount of an immunogenic composition, wherein said immunogenic composition comprises Proteosomes, liposaccharide and one or more botulinum toxin antigens or fragments or variant thereof, wherein the botulinum toxin antigen elicits a neutralizing antibody response.
  • nucleic acid molecules or polypeptide present in a living animal or cell, or virus is not isolated, but the same nucleic acid molecule or polypeptide is isolated when separated from some or all of the co-existing materials in the natural system.
  • nucleic acid molecules could be contained in a vector or such nucleic acids could be part of a composition and still be isolated in that such a vector or composition is not part of the original nucleic acid molecule's natural environment.
  • peptides or polypeptides such as antigens or variants and fragments thereof, may be either partially purified or purified to homogeneity.
  • the present invention further provides methods for producing synthetic antigens, including fusion proteins.
  • the immunogenic polypeptide components may be synthesized by standard chemical methods, including synthesis by automated procedure. In general, immunogenic polypeptides or peptides are synthesized based on the standard solid-phase Fmoc protection strategy with HATU as the coupling agent.
  • the immunogenic peptide can be cleaved from the solid-phase resin with trifluoroacetic acid containing appropriate scavengers, which also deprotects side chain functional groups. Crude immunogenic peptide may be further purified using preparative reverse phase chromatography. Other purification methods, such as partition chromatography, gel filtration, gel electrophoresis, or ion-exchange chromatography may be used.
  • a mixture of at least one antigen with a Proteosome (projuvant) or Protollin is prepared in the presence of detergent, and reducing or removal of the detergent from the mixture by diafiltration/ultrafiltration leads to association (or coordination) of the antigens with the adjuvant.
  • the Protollin (or Proteosome) to antigen ratio in the mixture ranges from about 1 : 1 to about 5:1. The ratio can be as high as 8 : 1 or higher.
  • detergents can also be used (e.g., octoglucoside).
  • the detergents serve to solubilize the components used to prepare the composition.
  • the use of a mixture of detergents may be particularly advantageous. This mixture is, of course, removed or the concentration is reduced by diafiltration/ultrafiltration prior to final formulation.
  • the immunogenic compositions that contain one or more antigens and a Proteosome-based adjuvant of the invention may be in any form that allows for the composition to be administered to a subject, such as a human or animal.
  • immunogenic compositions of the present invention may be prepared and administered as a liquid solution or prepared as a solid form (e.g., lyophilized), which may be administered in solid form, or resuspended in a solution in conjunction with administration.
  • the immunogenic polypeptide compositions are formulated to allow the active ingredients contained therein to be bioavailable upon administration of the composition to a subject or patient or bioavailable via slow release.
  • the supernatants were stored at -70°C until assayed.
  • Lungs were lavaged twice with l.O mL protease supplemented PBS, the fluid was collected and vortexed, and the cell debris removed by centrifugation.
  • Lung and nasal washes were stored at -70°C until being assayed. Rabbit mucosal fluids were similarly collected, adjusting the volumes as appropriate.
  • cervical and mediastinal lymph nodes were surgically removed and mononuclear cells isolated and cultured for ELISPOT antibody, cytokine and CMI assays as described herein.
  • Proteosome:LPS Protollin
  • Fl-V plague antigen
  • the Fl-V immune response was assessed by immunizing groups of twenty 6-8 week old female Swiss- Webster mice (Charles River, St-Constant, Quebec) on days 0 and 21. For immunization, freshly thawed aliquots of Protollin and Fl-V solutions were mixed ⁇ 16 hrs prior to immunization.
  • mice were first lightly anesthetized by isoflurane inhalation, then 25 ⁇ l of vaccine or appropriate control samples (Protollin or Fl-V alone) was applied to the nares (12.5 ⁇ l per nostril) of each mouse.
  • mice were immunized intramuscular (i.m.) with 25 ⁇ l ) of Fl-V adsorbed to 500mg of Alhydrogel injected into hind limbs. Control i.m. injections were also performed. Thirty-five and 55 days thereafter, 10 mice from each group were euthanized by asphyxiation with CO 2 and exsanguination. Serum was obtained and stored at -80°C until assay.
  • Antibodies present in serum and lung lavage fluid samples obtained from mice immunized intranasally with two doses of Fl-V antigen formulated with Protollin were compared with those from mice immunized i.n. with Fl-V alone or with mice

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Microbiology (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Mycology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Virology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des méthodes de préparation et d'utilisation de formulations thérapeutiques de compositions immunoactives à base de protéosomes.
EP04760725A 2003-05-05 2004-05-05 Vacciner contre des maladies infectieuses utilisant des proteosomes Withdrawn EP1622641A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US46762403P 2003-05-05 2003-05-05
PCT/US2004/014236 WO2004098636A2 (fr) 2003-05-05 2004-05-05 Compositions a base de proteosomes utilisees comme vaccin contre des maladies infectieuses

Publications (1)

Publication Number Publication Date
EP1622641A2 true EP1622641A2 (fr) 2006-02-08

Family

ID=33435094

Family Applications (1)

Application Number Title Priority Date Filing Date
EP04760725A Withdrawn EP1622641A2 (fr) 2003-05-05 2004-05-05 Vacciner contre des maladies infectieuses utilisant des proteosomes

Country Status (5)

Country Link
EP (1) EP1622641A2 (fr)
JP (1) JP2006525373A (fr)
AU (1) AU2004235815A1 (fr)
CA (1) CA2524485A1 (fr)
WO (1) WO2004098636A2 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7255867B2 (en) 2002-11-15 2007-08-14 Id Biomedical Corporation Of Quebec Vaccine
CA2543080C (fr) 2003-10-22 2019-01-08 Id Biomedical Corporation Of Quebec Compositions et procedes pour activer une immunite innee et une immunite aux allergies
JP2010502747A (ja) * 2006-09-08 2010-01-28 ベクトン・ディキンソン・アンド・カンパニー ミョウバン吸着ワクチンの安定粉末製剤

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU784131B2 (en) * 1999-12-22 2006-02-09 Darrell R. Galloway Methods for protecting against lethal infection with bacillus anthracis
MXPA03008154A (es) * 2001-03-09 2004-11-12 Id Biomedical Corp Quebec Novedoso adyuvante de vacuna de proteosoma-liposacarido.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2004098636A2 *

Also Published As

Publication number Publication date
WO2004098636A8 (fr) 2005-08-18
WO2004098636A2 (fr) 2004-11-18
WO2004098636A3 (fr) 2005-05-19
JP2006525373A (ja) 2006-11-09
CA2524485A1 (fr) 2004-11-18
AU2004235815A1 (en) 2004-11-18

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