WO1998058966A1 - Composition pour immuniprotection specifique et procede d'obtention de ladite composition - Google Patents

Composition pour immuniprotection specifique et procede d'obtention de ladite composition Download PDF

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Publication number
WO1998058966A1
WO1998058966A1 PCT/IB1997/000768 IB9700768W WO9858966A1 WO 1998058966 A1 WO1998058966 A1 WO 1998058966A1 IB 9700768 W IB9700768 W IB 9700768W WO 9858966 A1 WO9858966 A1 WO 9858966A1
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WO
WIPO (PCT)
Prior art keywords
receptor
specific
antibodies
obtaining
pathogen
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Application number
PCT/IB1997/000768
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English (en)
Inventor
Norman Godin
Original Assignee
Norman Godin
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 Norman Godin filed Critical Norman Godin
Priority to AU30446/97A priority Critical patent/AU3044697A/en
Priority to PCT/IB1997/000768 priority patent/WO1998058966A1/fr
Publication of WO1998058966A1 publication Critical patent/WO1998058966A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2812—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere

Definitions

  • This invention relates to a composition for specific immunoprotection against (a) disease-causing pathogen(s) in order to prevent and treat human or animal infections caused by known pathogens such a s bacteria, viruses, mycoplasma, parasites, fungi, etc.
  • HIV Human Immunodeficiency Virus
  • the composition according to th e invention is characterized in that the composition comprises at least one antibody component reacting with at least one antigenic epitope of a t least one active site of at least one specific receptor known to be u sed by said pathogen to penetrate at least one target cell, so as to provide for immunity to said pathogen.
  • the active part of the receptor is defined as the part of the receptor that binds to its ligand.
  • the new concept of the present invention is to start the composition of this "immunoprotector" with the active part of the specific receptor(s), several receptors if the pathogen uses several receptors to bind and penetrate into target cells as is now known for HIV infection or only one receptor if only one specific receptor is thought to be involved in the cycle of a pathogen as seems to be the case in malaria infection for each type of Plasmodium (falciparum, vivax, etc..) see "The Duffy antigen/receptor for chemokines or DARC as chemokine receptor on the erythroid lineage and as the invasin for the malaria-causing protozoan Plasmodium vivax", in Chemokine receptors, Murphy PM.
  • this "immunoprotector" from the pathogen, parts of the pathogen or its toxins or proteins from the pathogen obtained by purification or genetic engineering or antibodies to the pathogen or DNA coding for some part of the antigen but from the specific receptors on target cells known to be used by th e pathogen for infecting the target cell(s).
  • the specific immunoprotection obtained by these preventive and therapeutic agents originate from the specific receptor(s) used by the pathogen which are the basis for these agents, which one could also describe as "receptor immunoprotectors".
  • the invention further relates also to a method adapted for obtaining a composition for specific immunoprotection against a disease causing pathogen and for this purpose is characterized by the following stages
  • the method for obtaining this "immunoprotector" composition does not require the use in any form of the pathogen, directly or even indirectly as in anti-idiotypic vaccines where antibodies to the pathogen (Abl ) are obtained and then antibodies (Ab 2) or so called internal images of the antigen are obtained.
  • the method may comprise the following steps
  • composition In this composition, one starts with all specific receptors involved in the disease and particularly their active part defined as the part of the receptor binding to the ligand(s) and obtains (an) antibody (-ies) to this (these) receptors in animals (polyclonal and/or monoclonal) so as to "mimic the ligand to this (these) particular receptor(s)", thus obtaining a specific antibody or specific antibodies mimicking the ligand(s) to this particular receptor, the composition intends to mimic the ligand part of the pathogen that binds to the specific receptors including all possible mutations of the ligand still capable to actively binding to the active part of the receptor(s).
  • the antibody(ies) to the antigenic epitope(s) of the specific part of the receptor will mimic the ligand.
  • Using this (or these) antibody(-ies) as vaccination or therapeutic agents by immunization will create internal images of the active part of the receptors in the B and T cell repertoires as well as specific antibodies and cytotoxic T cells to the pathogen(s), particularly after 2 or 3 boosting shots as is usually done with most conventional existing vaccines.
  • the host's immune system will be able to mount a rapid, specific immune response to the pathogen, creating internal images of the receptor(s) on its T and B cell repertoires as well as specific antibodies and cytotoxic T cells that will react with the specific ligand(s) of the pathogen and help eliminate it.
  • Several antibodies to the active part of the receptor might be necessary so as to cover any possible changes or mutations of the part of the pathogen mimicking the ligand.
  • the invention is adapted for specific immunoprotection against the human immunodeficiency virus (HIV), the agent known to cause the Acquired Immunodeficiency Syndrome or AIDS.
  • HIV human immunodeficiency virus
  • fusin The first co-receptor described by Feng et al. (Science, May 1996, 272, 872- 876) is called fusin, it is a receptor for an A chemokine.
  • This fusin receptor also denominated CX-CR3 appears to be a co-factor with the CD4 receptor for entry of HIV- 1 viruses in CD4+ T cells either directly or possibly indirectly acting through the G protein-coupled receptor.
  • Recombinant fusin enabled CD4-expressing nonhuman cell types, usually resistant to HIV1 infection to support H ⁇ V-1 Env-mediated cell fusion and HIV-1 infection.
  • Antibodies to the NH-2 terminus of fusin blocked infection of normal CD-4 positive human target cells. Fusin acted preferentially for T cell line-tropic isolates of HIV.
  • fusin is an «orphan» receptor, that is to this date no normal physiological ligand has been determined for this receptor.
  • the other receptor is the chemokine receptor CCR-5 or CKR-5 on macrophages, for which the gene has been cloned by Samson et al.(Biochemistry 1996, 35, 3362-3367).
  • This receptor seems to play a major role for infection of macrophages by HIV-1 in sexually transmitted disease, while the previous receptor fusine plays a role later in the disease when the number of CD4+ cells start to decline. It has been demonstrated that individuals bearing mutant alleles of the CCR-5 chemokine receptor gene are resistant to HIV-1 infection, demonstrating the importance of this receptor in infection by HIV-1, See Samson et al. (Nature 1996, 382, 722-725) and Liu et al.(Cell 1996, 86, 367-377).
  • the CCR- 5 receptor playing a major role in vitro and in vivo as individuals with a deficient receptor (homozygotes) seem to be protected from HIV-1 infection and heterozygotes are at lower risk of becoming seropositive.
  • the CCR-5 on macrophages play a major role early on in the disease process, when HIV virus are M-tropic for macrophages trophic and play a major role in sexually transmitted disease while the CD4 and fusine receptors play a role later in the disease evolution when the CD4 cells start to decrease.
  • T- tropic strains of HIV use the fusin and CD4 receptors and may play an important role in intravenous routes of infection.
  • the process of manufacturing a HIV immunoprotector involves favorably the following stages:
  • the receptors could be obtained by genetic engineering. This is particularly true for the CD4 receptors, the fusine family of receptors and the CCR-5 receptor gene. These genes can be expressed in known systems as E coli, baculovims, yeast, etc... (see: A. Metabohc engineering of E. CoM to enhance recombinant protein production through acetate reduction. Aristidou AA: Biotechnol Prog, 1995 Jul-Aug. B. A novel host- vector system for direct selection of recombinant baculoviruses in E. CoU. Leusch MS; Gene, 1995 Jul 28.
  • (A) monoclonal antibody(-ies) can be obtained from these purified receptors as described by Kohler G. and Milstein C (Nature 1975; 256: 495-497). Generally such antibodies are produced by immunizing an animal with the purified receptors, obtaining antibody producing cells from the animal, and fusing the antibody producing cells with strains of myeloma cells, e.g., tumor cells, to produce hybridomas which are isolated and cultured as monoclones.
  • the monoclonal hybridomas may either be cultured in vitro or may be grown as tumors in a host animal.
  • each antibody-producing cell produces a single unique antibody
  • the monoclonal cultures of hybridomas each produce a homogeneous antibody which may be obtained either from the culture medium of hybridoma cultures grown in vitro or from the cells, ascitic fluid, or serum of a tumor bearing host animal.
  • polyclonal antibodies or monoclonal antibodies can be done by one of several methods, in particular ammonium sulphate precipitation and size/exclusion chromatography, by protein A- and protein G- sepharose affinity chromatography using columns and discs, or better by affinity chromatography using columns carrying the specific receptors for which antibodies are purified or by ion-exchange chromatography. Details for purification procedures can be found in Section HI, unit 2.7, Current protocols in immunology, 1991, same reference as above.
  • the antibody (-ies) obtained are mixed with at least one adjuvant such aluminum hydroxyde, aluminum phophate, calcium phophate and oil emulsions or one of the following alternative adjuvants such as derivatives of muramyl dipeptide, monophophoryl lipid A, liposomes, QS21, MF-59 and immunostimulating complexes (ISCOMS). See Adjuvants for human vaccines-current status, problems and future prospects Gupta RK and Siber G.R in Vaccine 1995, Volume 13 Number 14 1263-1276.
  • adjuvants such as derivatives of muramyl dipeptide, monophophoryl lipid A, liposomes, QS21, MF-59 and immunostimulating complexes (ISCOMS).
  • a conservative agent such as Thiomersal or 2-phenoxyehanol for example can be added. Repeated booster shots at one, two and six months are necessary in order to confer immunity.
  • a similar method can be used for a large number of pathogens, as long as the corresponding specific receptors are determined.
  • a few examples are given hereafter which are only a few examples of many possible specific immunoprotectors that can be made, this list is in no way comprehensive as many more specific immunoprotectors can be considered as long as the specific receptor(s) to the pathogen have been determined.
  • Some specific receptors have been determined for adenoviruses type 2, for influenza viruses, coronaviruses, parvo viruses, arboviruses, vesicular stomatitis viruses, etc... See Patterson S and Oxford J. S Early virus-cell interactions Vaccine Vol.4 June 1986.
  • composition adapted for specific immunoprotection against infectious mononucleosis comprises (an) antibody(ies) to the active sites of the C3d receptor comprising the CR2 and CD21 antigens.
  • a composition adapted for specific immunoprotection against malaria comprises antibodies to the active sites of red cell sialoglycoproteins and the Duffy antigen/receptor for chemokines (DARC).
  • a composition adapted for specific immunoprotection against influenza comprises antibodies to the active sites of sialyloligosaccharides.
  • a composition adapted for specific immunoprotection against arboviruses comprises antibodies to the active sites of phosophatidylinositol and polyphophoinositides.
  • a composition adapted for specific immunoprotection against vesicular stomatitis viruses comprises antibodies to the active sites of phosphatidylserine.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne un procédé spécifiquement adapté pour la fabrication d'une composition d'immunoprotection spécifiquement dirigée contre un antigène pathogène. Le procédé consiste: 1) à déterminer les récepteurs spécifiques liés à la pathologie; 2) à obtenir des anticorps, des fragments monoclonaux ou polyclonaux de ces anticorps, dirigés contre les épitopes antigènes de la partie active des récepteurs; 3) et à ajouter au moins un adjuvant stimulant l'immunité. La composition ainsi obtenue protège les récepteurs contre toutes les souches existantes et toutes les souches mutantes futures possibles d'agents pathogènes restant capables de se lier à ces récepteurs. La composition ne nécessite par l'utilisation directe ou indirecte d'agents pathogènes. Une réalisation particulière avantageuse de l'invention est adaptée pour l'obtention d'une composition conférant une immunoprotection spécifique dirigée contre le syndrome d'immunodéficience acquise (SIDA).
PCT/IB1997/000768 1997-06-24 1997-06-24 Composition pour immuniprotection specifique et procede d'obtention de ladite composition WO1998058966A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU30446/97A AU3044697A (en) 1997-06-24 1997-06-24 A composition for specific immunoprotection and method for obtaining said comp osition
PCT/IB1997/000768 WO1998058966A1 (fr) 1997-06-24 1997-06-24 Composition pour immuniprotection specifique et procede d'obtention de ladite composition

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB1997/000768 WO1998058966A1 (fr) 1997-06-24 1997-06-24 Composition pour immuniprotection specifique et procede d'obtention de ladite composition

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WO1998058966A1 true WO1998058966A1 (fr) 1998-12-30

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6511826B2 (en) 1995-06-06 2003-01-28 Human Genome Sciences, Inc. Polynucleotides encoding human G-protein chemokine receptor (CCR5) HDGNR10
US6743594B1 (en) 1995-06-06 2004-06-01 Human Genome Sciences, Inc. Methods of screening using human G-protein chemokine receptor HDGNR10 (CCR5)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0240344A2 (fr) * 1986-04-02 1987-10-07 The Wellcome Foundation Limited Anticorps monoclonaux et leur application
EP0409242A1 (fr) * 1989-07-21 1991-01-23 The Calpis Food Industry Co., Ltd. Anticorps monoclonal contre un peptide du CD4 humain
WO1992009305A1 (fr) * 1990-11-27 1992-06-11 Biogen, Inc. Anticorps anti-cd4 bloquant les syncytia provoques par le vih
WO1997009351A1 (fr) * 1995-09-06 1997-03-13 Idec Pharmaceuticals Corporation Anticorps anti-cd4 recombinants pour therapie humaine
WO1997045543A2 (fr) * 1996-05-28 1997-12-04 The Government Of The United States Of America, As Represented By The Secretary Of Health And Human Services, National Institutes Of Health Recepteur 5 de cc chemokine, anticorps diriges contre ce dernier et animaux transgeniques

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0240344A2 (fr) * 1986-04-02 1987-10-07 The Wellcome Foundation Limited Anticorps monoclonaux et leur application
EP0409242A1 (fr) * 1989-07-21 1991-01-23 The Calpis Food Industry Co., Ltd. Anticorps monoclonal contre un peptide du CD4 humain
WO1992009305A1 (fr) * 1990-11-27 1992-06-11 Biogen, Inc. Anticorps anti-cd4 bloquant les syncytia provoques par le vih
WO1997009351A1 (fr) * 1995-09-06 1997-03-13 Idec Pharmaceuticals Corporation Anticorps anti-cd4 recombinants pour therapie humaine
WO1997045543A2 (fr) * 1996-05-28 1997-12-04 The Government Of The United States Of America, As Represented By The Secretary Of Health And Human Services, National Institutes Of Health Recepteur 5 de cc chemokine, anticorps diriges contre ce dernier et animaux transgeniques

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6511826B2 (en) 1995-06-06 2003-01-28 Human Genome Sciences, Inc. Polynucleotides encoding human G-protein chemokine receptor (CCR5) HDGNR10
US6743594B1 (en) 1995-06-06 2004-06-01 Human Genome Sciences, Inc. Methods of screening using human G-protein chemokine receptor HDGNR10 (CCR5)
US6759519B2 (en) 1995-06-06 2004-07-06 Human Genome Sciences, Inc. Antibodies to human G-protein chemokine receptor HDGNR10 (CCR5receptor)
US6800729B2 (en) 1995-06-06 2004-10-05 Human Genome Sciences, Inc. Human G-Protein chemokine receptor HDGNR10 (CCR5 receptor)

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Publication number Publication date
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