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WO2002009748A1 - Vaccins diriges vers le systeme immunitaire inne - Google Patents

Vaccins diriges vers le systeme immunitaire inne Download PDF

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Publication number
WO2002009748A1
WO2002009748A1 PCT/US2001/024228 US0124228W WO0209748A1 WO 2002009748 A1 WO2002009748 A1 WO 2002009748A1 US 0124228 W US0124228 W US 0124228W WO 0209748 A1 WO0209748 A1 WO 0209748A1
Authority
WO
WIPO (PCT)
Prior art keywords
antigen
fusion protein
pamp
protein
vaccine
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.)
Ceased
Application number
PCT/US2001/024228
Other languages
English (en)
Other versions
WO2002009748A9 (fr
Inventor
Ruslan M. Ph. D. Medzhitov
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.)
Yale University
Original Assignee
Yale University
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
Priority claimed from US09/752,832 external-priority patent/US20020061312A1/en
Application filed by Yale University filed Critical Yale University
Priority to AU2001286405A priority Critical patent/AU2001286405B2/en
Priority to CA002418036A priority patent/CA2418036A1/fr
Priority to EP01965846A priority patent/EP1322326A4/fr
Priority to AU8640501A priority patent/AU8640501A/xx
Publication of WO2002009748A1 publication Critical patent/WO2002009748A1/fr
Priority to US10/353,316 priority patent/US20030232055A1/en
Anticipated expiration legal-status Critical
Publication of WO2002009748A9 publication Critical patent/WO2002009748A9/fr
Priority to US11/507,387 priority patent/US20070122421A1/en
Priority to US12/004,344 priority patent/US20080226667A1/en
Ceased 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
    • A61K39/385—Haptens or antigens, bound to carriers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing 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
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6025—Nucleotides
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention provides also provides a fusion protein comprising an isolated PAMP and an antigen, wherein the antigen is a self- antigen.
  • the present invention also provides methods of treating a patient susceptible to an allergic response to an allergen by administering a vaccine of the present invention and thereby stimulating the TLR-mediated signaling pathway.
  • Figure 11 shows that wild-type and BlO/ScCr dendritic cells, but not dendritic cells from MyD88 "/” animals produce IL-12 when stimulated with CpG oligonucleotides.
  • Figure 12 shows activation of NF- ⁇ B by Flagellin fusions.
  • Adaptive immune response refers to a response involving the characteristics of the “adaptive immune system” described above.
  • Adapter molecule refers to a molecule that can be transiently associated with some TLRs, mediates immunostimulation by molecules of the innate immune system, and mediates cytokine-induced signaling.
  • Adapter molecule includes, but is not limited to, myeloid differentiation marker 88 (MyD88).
  • Linker refers to any chemical entity that links one chemical moiety to another chemical moiety. Thus, something that chemically or physically connects a PAMP and an antigen is a linker.
  • linkers include, but are not limited to, complex or simple hydrocarbons, nucleosides, nucleotides, nucleotide phosphates, oligonucleotides, polynucleotides, nucleic acids, amino acids, small peptides, polypeptides, carbohydrates (e.g., monosaccharides, disaccharides, trisaccharides), and lipids. Additional examples of linkers are provided in the Detailed Description Selection included herein.
  • PAMP includes a PAMP, derivative or portion of a PAMP that is immunostimulatory, and any immunostimulatory molecule derived from any PAMP. These structures, or derivatives thereof, are potential initiators of innate immune responses, and therefore, ligands for PRRs, including Toll receptors and TLRs.
  • PAMP mimetic refers to a molecule that, although it does not occur in microorganisms, is analogous to a PAMP in that it can bind to a PRR and such binding can trigger an innate immune response.
  • a PAMP mimetic can be a naturally- occurring molecule or a partially or totally synthetic molecule.
  • certain plant alkaloids, such as taxol are PRR ligands, have an immunostimulatory effect on the innate immune system, and thus behave as PAMP mimetics. (Kawasaki et al. (2000) J. Biol. Chem. 275(4): 2251-2254).
  • Tumor refers to a mass of proliferating cells lacking, to varying degrees, normal growth control. As used herein, “tumors'' include, at one extreme, slowly proliferating “benign” tumors, to, at the other extreme, rapidly proliferating “malignant” tumors that aggressively invade neighboring tissues.
  • Vaccine refers to a composition comprising an antigen, and optionally other ancillary molecules, the purpose of which is to administer such compositions to a subject to stimulate an immune response specifically against the antigen and preferably to engender immunological memory that leads to mounting of an immune response should the subject encounter that antigen at some future time.
  • ancillary molecules are adjuvants, which are non-specific immunostimulatory molecules, and other molecules that improve the pharmacokinetic and or pharmacodynamic properties of the antigen.
  • a vaccine usually consists of the organism that causes a disease (suitably attenuated or killed) or some part of the pathogenic organism as the antigen.
  • tetani mumps, Morbillivirus, Herpes Simplex Virus type 1, Herpes Simplex Virus type 2, Human cytomegalovirus, Hepatitis A Virus, Hepatitis B Virus, Hepatitis C Virus, Hepatitis E Virus, Respiratory Syncytial Virus, Human Papilloma Virus, Influenza Virus, Salmonella, Neisseria, Borrelia, Chlamydia, Bordetella, and Plasmodium and Toxoplasma, Cryptococcus, Streptococcus, Staphylococcus, Haemophilus, Diptheria, Tetanus, Pertussis, Escherichia, Candida, Aspergillus, Entamoeba, Giardia, and Trypanasoma.
  • tumor-related or tissue-specific protein antigens useful in such vaccines include, but are not limited to, antigens selected from the group in the following table.
  • linker peptides might be to direct cleavage of the antigen in intracellular processing so as to facilitate peptide presentation on the surface of the APC.
  • Appropriate cleavage sites might be inserted via linkers such that the fusion protein is not cleaved until it is internalized by the APC. Under such circumstances, such a peptide cleavage site can be introduced via a linker between the PAMP and the antigen to generate intracellular antigen free of PAMP.
  • Such directed cleavage could also be used particularly to facilitate production within the APC of specific peptides that have been identified as interacting with particular HLA haplotypes.
  • different domains from a single antigen or from more than one antigen might be separated by linkers containing cleavage sites so that these epitopes could be appropriately processed for presentation on the surface of the APC.
  • Vectors that include a prokaryotic replicon can further include a prokaryotic or viral promoter capable of directing the expression (transcription and translation) of the PAMP/antigen fusion in a bacterial host cell, such as E. coli.
  • a promoter is an expression control element formed by a nucleic acid sequence that permits binding of RNA polymerase and transcription to occur. Promoter sequences compatible with bacterial hosts are typically provided in plasmid vectors containing convenient restriction sites for insertion of a nucleic acid segment of the present invention.
  • the gene gun has also been used to successfully deliver plasmid DNA for inducing immunity against an intracellular pathogen for which protection primarily depends on type 1 CD ⁇ .sup. + T-cells.
  • Gene transfer-mediated vaccination methods have become a rapidly expanding field and the compositions of the present invention are applicable to the treatment of both noninfectious and infectious diseases and noninfectious diseases, including but not limited to genetic disorders, using such vaccination methods.
  • Eck et al. (1996) Gene-Based Therapy, In: Goodman & Gihnan's The Pharmacological Basis of Therapeutics, Ninth Edition, Chapter 5, McGraw Hill).
  • compositions can take the form of solutions, suspensions, tablets, pills, capsules, sustained release formulations or powders and contain about 1 to 95% of the chimeric construct.
  • the vaccines are administered in a manner compatible with the dosage formulation, and in such amount as will be therapeutically effective, protective and immunogenic dosages.
  • the quantity of vaccine employed will of course vary depending upon the patient's age, weight, height, sex, general medical condition, previous medical history, the condition being treated and its severity, and the capacity of the individual's immune system to synthesize antibodies, and produce a cell-mediated immune response.
  • it is desirable to provide the recipient with a dosage of the chimeric construct which is in the range of from about 1 ⁇ g agent /kg body weight of
  • recombinant vaccine product can be generated using a bacterial expression system.
  • the product can be purified from bacterial cultures using standard techniques. The approach is thus extremely economical and cost efficient.
  • recombinant vaccine product can be produced and purified from cultures of yeast or other eukaryotic cells including, without limitation, insect cells or mammalian cells.
  • Conjugated non-protein vaccine product can also be produced chemically in relatively large amounts. This is particularly the case if the PAMP and the antigen can both be obtained by relatively straightforward purification procedures and then conjugated together with relatively simple and efficient conjugation chemistry.
  • B-cells were prepared as above and cultured at 3 x IO 6 cells/ml with or without 10 mM CpG for 12 h. After the stimulation, the surface expression of CD86 and MHC class II were analyzed by flow cytometry. Results, shown in Figure 9B, represent gated B-cells. The shaded area represents stimulated cells, whereas the unshaded area represents untreated controls. As shown in Figure 9B, CpG-DNA strongly induced expression of CD86 and MHC class-II on B-cells from wild-type and TLR4-deficient mice. By contrast, this induction was completely abrogated in MyD88 deficient B-lymphocytes.
  • Flagellin Full-length Salmonella typhimurium Flagellin and E coli Flagellin were cloned from the respective genomic DNAs and expressed as recombinant proteins in E coli . Flagellin was expressed alone, or as a fusion protein with antigenic epitopes from ovalbumin (SIINFEKL), tyrosinase-2 protein (TRP2) cloned from murine B16 cells,

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne de nouveaux vaccins, des procédés servant à préparer ces vaccins et des procédés servant à utiliser ces vaccins. Ces nouveaux vaccins combinent à la fois les signaux nécessaires pour activer des lymphocytes T natifs - un antigène spécifique et le signal de stimulation conjointe, ce qui permet d'obtenir une réponse immune catégorique et spécifique des lymphocytes T.
PCT/US2001/024228 2000-07-31 2001-07-31 Vaccins diriges vers le systeme immunitaire inne Ceased WO2002009748A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
AU2001286405A AU2001286405B2 (en) 2000-07-31 2001-07-31 Innate immune system-directed vaccines
CA002418036A CA2418036A1 (fr) 2000-07-31 2001-07-31 Vaccins diriges vers le systeme immunitaire inne
EP01965846A EP1322326A4 (fr) 2000-07-31 2001-07-31 Vaccins diriges vers le systeme immunitaire inne
AU8640501A AU8640501A (en) 2000-07-31 2001-07-31 Innate immune system-directed vaccines
US10/353,316 US20030232055A1 (en) 2000-07-31 2003-01-29 Innate immune system-directed vaccines
US11/507,387 US20070122421A1 (en) 2000-07-31 2006-08-21 Innate immune system-directed vaccines
US12/004,344 US20080226667A1 (en) 2000-07-31 2007-12-20 Innate immune system-directed vaccines

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US22204200P 2000-07-31 2000-07-31
US60/222,042 2000-07-31
US25832900P 2000-12-28 2000-12-28
US60/258,329 2000-12-28
US09/752,832 US20020061312A1 (en) 2000-07-31 2001-01-03 Innate immune system-directed vaccines
US09/752,832 2001-01-03
US28260401P 2001-04-09 2001-04-09
US60/282,604 2001-04-09

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US09/752,832 Continuation-In-Part US20020061312A1 (en) 2000-07-31 2001-01-03 Innate immune system-directed vaccines

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US10/353,316 Continuation US20030232055A1 (en) 2000-07-31 2003-01-29 Innate immune system-directed vaccines

Publications (2)

Publication Number Publication Date
WO2002009748A1 true WO2002009748A1 (fr) 2002-02-07
WO2002009748A9 WO2002009748A9 (fr) 2003-04-03

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PCT/US2001/024228 Ceased WO2002009748A1 (fr) 2000-07-31 2001-07-31 Vaccins diriges vers le systeme immunitaire inne

Country Status (5)

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EP (1) EP1322326A4 (fr)
CN (1) CN1549726A (fr)
AU (2) AU2001286405B2 (fr)
CA (1) CA2418036A1 (fr)
WO (1) WO2002009748A1 (fr)

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002085933A1 (fr) * 2001-04-20 2002-10-31 The Institute For Systems Biology Ligands de recepteur de type 5 et procedes d'utilisation
WO2005042017A1 (fr) * 2003-10-22 2005-05-12 Id Biomedical Corporation Of Quebec Compositions et procedes pour activer une immunite innee et une immunite aux allergies
US7759068B2 (en) 2002-04-15 2010-07-20 Proteosys Ag Use of substances for treating tumors
US7879810B2 (en) 1994-07-15 2011-02-01 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
US7956043B2 (en) 2002-12-11 2011-06-07 Coley Pharmaceutical Group, Inc. 5′ CpG nucleic acids and methods of use
US8409580B2 (en) 2003-07-25 2013-04-02 Ac Immune Sa Therapeutic vaccine targeted against P-glycoprotein 170 for inhibiting multidrug resistance in the treatment of cancers
US8420102B2 (en) 2006-03-07 2013-04-16 Vaxinnate Corporation Compositions that include hemagglutinin
EP2650311A2 (fr) 2007-11-27 2013-10-16 Ablynx N.V. Séquences d'acides aminés dirigées contre des cytokines hétérodimériques et/ou leurs récepteurs et polypeptides les comprenant
US8574599B1 (en) 1998-05-22 2013-11-05 Ottawa Hospital Research Institute Methods and products for inducing mucosal immunity
US8703146B2 (en) 2001-04-20 2014-04-22 Institute For Systems Biology Toll-like receptor 5 ligands and methods of use
US8926983B2 (en) 2003-02-21 2015-01-06 Ac Immune Sa Method for improving memory in AD patients
US8932605B2 (en) 2008-04-18 2015-01-13 Vaxinnate Corporation Deletion mutants of flagellin and methods of use
US8932598B2 (en) 2012-08-28 2015-01-13 Vaxinnate Corporation Fusion proteins and methods of use
US9234009B2 (en) 2005-01-19 2016-01-12 Vaxinnate Corporation Methods of stimulating protective immunity employing Dengue viral antigens
US9289488B2 (en) 2010-08-12 2016-03-22 Ac Immune Sa Vaccine engineering
US9687447B2 (en) 2010-10-26 2017-06-27 Ac Immune S.A. Method for preparing liposome-based constructs
JP2018521632A (ja) * 2015-06-02 2018-08-09 デ スタート デル ネーデルランデン， ヴェルト． ドール デ ミニステル ヴァン ヴイダブリューエス ミニステリー ヴァン ボルクスゲツォントヘイト， ベルジーン エン シュポルトＤｅ Ｓｔａａｔ Ｄｅｒ Ｎｅｄｅｒｌａｎｄｅｎ， Ｖｅｒｔ． Ｄｏｏｒ Ｄｅ Ｍｉｎｉｓｔｅｒ Ｖａｎ Ｖｗｓ Ｍｉｎｉｓｔｅｒｉｅ Ｖａｎ Ｖｏｌｋｓｇｅｚｏｎｄｈｅｉｄ， Ｗｅｌｚｉｊｎ Ｅｎ Ｓｐｏｒｔ グラム陰性外膜小胞における抗原の表面提示
US10206985B2 (en) 2013-02-05 2019-02-19 Nitto Denko Corporation WT1 peptide cancer vaccine composition for mucosal administration
US11226340B2 (en) 2016-04-26 2022-01-18 Qu Biologics Inc. Therapeutically triggering an innate immune response in a target tissue

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CN105209054A (zh) * 2013-04-18 2015-12-30 阿尔莫生物科技股份有限公司 使用白细胞介素-10治疗疾病和病症的方法
BR112018007474A2 (pt) * 2015-10-14 2018-10-30 Novozymes A/S ?limpeza de membranas de filtração de água?
ES2990113T3 (es) * 2016-07-07 2024-11-28 The Board Of Trustees Of The Leland Stanfordjunior Univ Conjugados de adyuvantes de anticuerpos
CN112940135B (zh) * 2019-12-11 2025-06-27 四川农业大学 融合蛋白、其氨基酸序列、编码核苷酸序列、制备方法和应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0540128A1 (fr) * 1988-09-26 1993-05-05 Biotechnology Australia Pty. Ltd. Vaccin contre les nématodes
US5601831A (en) * 1989-03-09 1997-02-11 Praxis Biologics, Inc. Vaccines for nontypable Haemophilus influenzae
WO1997006590A1 (fr) * 1995-08-09 1997-02-20 Siemens Aktiengesellschaft Systeme permettant de compenser les courants d'harmoniques d'une voie de transmission composee de plusieurs conducteurs
US5693495A (en) * 1990-08-08 1997-12-02 Biomay Produktions- Und Handelsgesellschaft M.B.H. Allergens of alder pollen and applications thereof
US5877289A (en) * 1992-03-05 1999-03-02 The Scripps Research Institute Tissue factor compositions and ligands for the specific coagulation of vasculature

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1331355C (fr) * 1986-04-21 1994-08-09 Bioenterprises Pty. Ltd Immunopotentialisation
KR19990007858A (ko) * 1995-04-17 1999-01-25 존 더블유.로우 박테리아의 리포프로테인으로 폴리사카라이드에 대한 면역반응의 유도및 강화
US6251405B1 (en) * 1995-06-07 2001-06-26 Connaught Laboratories, Inc. Immunological combination compositions and methods
AU744730B2 (en) * 1998-02-06 2002-02-28 Research Development Foundation Live vaccine for human immunodeficiency virus
AU3005499A (en) * 1998-03-16 1999-10-11 Henry M. Jackson Foundation For The Advancement Of Military Medicine Induction and enhancement of the immune response to type-2 cell-independent antigens conjugated to lipid or lipid-containing moieties
FR2776521B1 (fr) * 1998-03-27 2000-12-15 Pf Medicament Utilisation de conjugues p40 actifs par voie nasale

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0540128A1 (fr) * 1988-09-26 1993-05-05 Biotechnology Australia Pty. Ltd. Vaccin contre les nématodes
US5601831A (en) * 1989-03-09 1997-02-11 Praxis Biologics, Inc. Vaccines for nontypable Haemophilus influenzae
US5693495A (en) * 1990-08-08 1997-12-02 Biomay Produktions- Und Handelsgesellschaft M.B.H. Allergens of alder pollen and applications thereof
US5877289A (en) * 1992-03-05 1999-03-02 The Scripps Research Institute Tissue factor compositions and ligands for the specific coagulation of vasculature
WO1997006590A1 (fr) * 1995-08-09 1997-02-20 Siemens Aktiengesellschaft Systeme permettant de compenser les courants d'harmoniques d'une voie de transmission composee de plusieurs conducteurs

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
MEEKER A. ET AL.: "A fusion protein between serum amyloid A and staphylococcal nuclease - synthesis, purification and structural studies", PROTEINS, vol. 30, no. 4, March 1998 (1998-03-01), pages 381 - 387, XP002949604 *
NAKAMURA K. ET AL.: "DNA sequence of the gene for the outer membrane lipoprotein of E. coli and extremely AT-rich promoter", CELL, vol. 18, December 1979 (1979-12-01), pages 1109 - 1117, XP002949603 *
See also references of EP1322326A4 *
VERMA N. ET AL.: "Delivery of class I and class II MHC-restricted T-cell epitopes of listeriolysin of listeria monocytogenes by attenuated salmonella", VACCINE, vol. 13, no. 2, 1995, pages 142 - 150, XP002949605 *

Cited By (31)

* Cited by examiner, † Cited by third party
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US7879810B2 (en) 1994-07-15 2011-02-01 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
US8574599B1 (en) 1998-05-22 2013-11-05 Ottawa Hospital Research Institute Methods and products for inducing mucosal immunity
US9085616B2 (en) 2001-04-20 2015-07-21 The University For Systems Biology Toll-like receptor 5 ligands and methods of use
US7915381B2 (en) 2001-04-20 2011-03-29 Institute For Systems Biology Toll-like receptor 5 ligands and methods of use
WO2002085933A1 (fr) * 2001-04-20 2002-10-31 The Institute For Systems Biology Ligands de recepteur de type 5 et procedes d'utilisation
US8703146B2 (en) 2001-04-20 2014-04-22 Institute For Systems Biology Toll-like receptor 5 ligands and methods of use
US7759068B2 (en) 2002-04-15 2010-07-20 Proteosys Ag Use of substances for treating tumors
US7956043B2 (en) 2002-12-11 2011-06-07 Coley Pharmaceutical Group, Inc. 5′ CpG nucleic acids and methods of use
US8926983B2 (en) 2003-02-21 2015-01-06 Ac Immune Sa Method for improving memory in AD patients
US8409580B2 (en) 2003-07-25 2013-04-02 Ac Immune Sa Therapeutic vaccine targeted against P-glycoprotein 170 for inhibiting multidrug resistance in the treatment of cancers
US8173140B2 (en) 2003-10-22 2012-05-08 Id Biomedical Corporation Of Quebec Compositions and methods for activating innate and allergic immunity
WO2005042017A1 (fr) * 2003-10-22 2005-05-12 Id Biomedical Corporation Of Quebec Compositions et procedes pour activer une immunite innee et une immunite aux allergies
US8709447B2 (en) 2003-10-22 2014-04-29 Id Biomedical Corporation Of Quebec Compositions and methods for activating innate and allergic immunity
EP2174665A3 (fr) * 2003-10-22 2010-06-23 ID Biomedical Corporation of Quebec Compositions et méthodes pour l'activation de l'immunité innée et allergique
US9975946B2 (en) 2004-02-20 2018-05-22 Ac Immune Sa Antibodies obtainable using supramolecular constructs
US9234009B2 (en) 2005-01-19 2016-01-12 Vaxinnate Corporation Methods of stimulating protective immunity employing Dengue viral antigens
US9446115B2 (en) 2005-01-19 2016-09-20 Vaxinnate Corporation Methods of stimulating immunity employing dengue viral antigens
US8945579B2 (en) 2006-03-07 2015-02-03 Vaxinnate Corporation Methods of treatment with compositions that include hemagglutinin
US8420102B2 (en) 2006-03-07 2013-04-16 Vaxinnate Corporation Compositions that include hemagglutinin
US9056901B2 (en) 2006-03-07 2015-06-16 Vaxinnate Corporation Methods of making hemagglutinin proteins
US9969805B2 (en) 2007-11-27 2018-05-15 Ablynx N.V. Amino acid sequences directed against HER2 and polypeptides comprising the same for the treatment of cancers and/or tumors
EP2650311A2 (fr) 2007-11-27 2013-10-16 Ablynx N.V. Séquences d'acides aminés dirigées contre des cytokines hétérodimériques et/ou leurs récepteurs et polypeptides les comprenant
US8975382B2 (en) 2007-11-27 2015-03-10 Ablynx N.V. Amino acid sequences directed against HER2 and polypeptides comprising the same for the treatment of cancers and/or tumors
US8932605B2 (en) 2008-04-18 2015-01-13 Vaxinnate Corporation Deletion mutants of flagellin and methods of use
US9289488B2 (en) 2010-08-12 2016-03-22 Ac Immune Sa Vaccine engineering
US9687447B2 (en) 2010-10-26 2017-06-27 Ac Immune S.A. Method for preparing liposome-based constructs
US8932598B2 (en) 2012-08-28 2015-01-13 Vaxinnate Corporation Fusion proteins and methods of use
US10206985B2 (en) 2013-02-05 2019-02-19 Nitto Denko Corporation WT1 peptide cancer vaccine composition for mucosal administration
JP2018521632A (ja) * 2015-06-02 2018-08-09 デ スタート デル ネーデルランデン， ヴェルト． ドール デ ミニステル ヴァン ヴイダブリューエス ミニステリー ヴァン ボルクスゲツォントヘイト， ベルジーン エン シュポルトＤｅ Ｓｔａａｔ Ｄｅｒ Ｎｅｄｅｒｌａｎｄｅｎ， Ｖｅｒｔ． Ｄｏｏｒ Ｄｅ Ｍｉｎｉｓｔｅｒ Ｖａｎ Ｖｗｓ Ｍｉｎｉｓｔｅｒｉｅ Ｖａｎ Ｖｏｌｋｓｇｅｚｏｎｄｈｅｉｄ， Ｗｅｌｚｉｊｎ Ｅｎ Ｓｐｏｒｔ グラム陰性外膜小胞における抗原の表面提示
JP7008900B2 (ja) 2015-06-02 2022-02-10 イントラヴァック ビー．ブイ． グラム陰性外膜小胞における抗原の表面提示
US11226340B2 (en) 2016-04-26 2022-01-18 Qu Biologics Inc. Therapeutically triggering an innate immune response in a target tissue

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CA2418036A1 (fr) 2002-02-07
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