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WO2004011490A1 - Epitope immunologique de la souche vih type o et ses utilisations - Google Patents

Epitope immunologique de la souche vih type o et ses utilisations Download PDF

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Publication number
WO2004011490A1
WO2004011490A1 PCT/CN2002/000552 CN0200552W WO2004011490A1 WO 2004011490 A1 WO2004011490 A1 WO 2004011490A1 CN 0200552 W CN0200552 W CN 0200552W WO 2004011490 A1 WO2004011490 A1 WO 2004011490A1
Authority
WO
WIPO (PCT)
Prior art keywords
epitope
hiv
strain
amino acid
immunological epitope
Prior art date
Application number
PCT/CN2002/000552
Other languages
English (en)
Chinese (zh)
Inventor
Yinghua Chen
Xiaonan Dong
Yi Xiao
Original Assignee
Tsinghua University
Beijing Qingda Yinghua Bio-Tech Co., Ltd.
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 Tsinghua University, Beijing Qingda Yinghua Bio-Tech Co., Ltd. filed Critical Tsinghua University
Priority to AU2002325467A priority Critical patent/AU2002325467A1/en
Publication of WO2004011490A1 publication Critical patent/WO2004011490A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • 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
    • A61K39/12—Viral 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
    • A61K39/12—Viral antigens
    • A61K39/21—Retroviridae, e.g. equine infectious anemia virus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
    • C07K16/1036—Retroviridae, e.g. leukemia viruses
    • C07K16/1045—Lentiviridae, e.g. HIV, FIV, SIV
    • C07K16/1063—Lentiviridae, e.g. HIV, FIV, SIV env, e.g. gp41, gp110/120, gp160, V3, PND, CD4 binding site
    • 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
    • A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
    • 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
    • A61K2039/6081—Albumin; Keyhole limpet haemocyanin [KLH]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
    • C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
    • C12N2740/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • the invention relates to an immunological epitope of HIV type 0 strain and its application.
  • HIV-1 caused by an immune disease, there is no effective cure for complete cure, and no vaccine can prevent it.
  • the high variability of immunodeficiency viruses has been a challenge in the design of HIV vaccines and drugs.
  • HIV-1 membrane protein gpl60 precursor protein of membrane protein gpl20 and transmembrane protein gp41
  • antibodies can inhibit mucosal transmission of HIV-1 virus and mother-to-child transmission, and can clear HIV-1 virus in the blood (Nature Medicine 1999, 5: 204; Nature Medicine 2000, 6: 200; Nature Medicine 1999, 5: 211);
  • the epitope-specific monoclonal antibody to the primary neutralizing epitope ELDKWA on the transmembrane protein g p41 of human immunodeficiency virus (HIV-1) can inhibit in vitro Multiple HIV-1 strains infect target cells (J. Virology 1993, 67: 6642; AIDS Res. Human Retroviruses 1994, 10: 1651; AIDS 1996, 10: 587).
  • HIV-1 can escape the neutralization of neutralizing antibodies by restricting mutations in neutralizing epitopes (Immunity 10, 431-438, 1999).
  • ELDKWA is recognized as an important HIV-1 neutralizing epitope. This epitope is highly conserved, but certain restrictive mutations at the D or K site can make the virus escape the neutralizing effect of monoclonal antibodies.
  • the object of the present invention is to provide a new immunological epitope of HIV type 0 strain.
  • An immunological epitope of HIV type 0 strain includes two adjacent amino acid residues whose nitrogen terminus is aspartic acid and whose carbon terminus is glutamic acid.
  • the amino acid residue usually connected at the nitrogen end of the immunological epitope is leucine; the amino acid residue usually connected at the carbon end is tryptophan, and the amino acid residue sequence of the immunological epitope is LDEW.
  • the amino acid residue linked to the nitrogen terminal is usually glutamic acid, and the amino acid residue linked to the carbon terminal is alanine.
  • the amino acid residue sequence of the immunological epitope is ELDEWA.
  • the inventor's search of the HIV database found that the transmembrane protein gp41 of all HIV-1 virus type 0 strains carries the ELDEWA epitope (as shown in Table '1), However, other HIV-1 virus subtypes do not carry this epitope, further confirming that ELDEWA is a unique epitope of HIV-1 virus type 0 strain, which can be used as a target site for the identification and diagnosis of HIV-1 virus type 0 strain. As a target site for therapeutic drugs.
  • Table 1 Characteristic ELDEWA epitopes of HIV-1 virus type 0 strain
  • a second object of the present invention is to provide a monoclonal antibody capable of specifically binding to an immunological epitope of the HIV type 0 strain of the present invention.
  • Monoclonal mouse hybridoma cell line 14D9 murine monoclonal antibody 14D9 subtype: IgG1).
  • the mouse hybridoma cell line 14D9 was deposited on June 27, 2002 at the General Microbial Center of the China Microbial Species Collection Management Committee (CGMCC for short), and the accession number is CGMCC Na 0753. ⁇
  • the monoclonal antibody 14D9 produced by the mouse hybridoma cell line 14D9 can specifically recognize the ELDEWA-epitope specific to the transmembrane protein gp41 of HIV-1 virus type 0 strain, and does not recognize the ELDKWA carried by other HIV-1 virus subtypes. ELNKWA- and ELEKWA- epitopes.
  • Figure 1 is an electrophoresis image of a monoclonal antibody of the present invention after reaction with a recombinant, soluble gp41 fusion protein with different epitopes.
  • An epitope polypeptide containing an ELDEWA-epitope specific to the transmembrane protein gp41 of HIV-1 0 strain was artificially synthesized.
  • the epitope polypeptide contains 4 repeated ELDEWA-immunological epitopes, and the amino acid residue sequence is: CELDEWAGELDEWAGELDEWAGELDEWA;
  • He'J used MBS (nrmaleimidobenzoyHHiydroxy succinimide ester) to couple the epitope polypeptide with the carrier protein BSA;
  • Example 2 Specific identification of the ELDEWA-epitope of HIV-1 virus type 0 strain by the antibody of the present invention
  • the monoclonal antibody secreted by the hybridoma cell line 14D9 was subjected to an incubation reaction with recombinant, soluble gp41 fusion proteins with different epitopes.
  • the results are shown in Figure 1. From the results in the figure, it can be seen that the hybridoma cell line 14D9 secreted
  • the monoclonal antibody specifically recognizes the ELDEWA-epitope of HIV-1 virus type 0 strain.
  • A molecular weight protein
  • B the monoclonal antibody of the present invention recognizes rsgp41 (GST-rsgp41) with the ELDEWA epitope.
  • ELDE wA 42KD]
  • C The monoclonal antibody of the present invention does not recognize rsgp41 (GST—rsgp41 EL
  • D The monoclonal antibody of the present invention does not recognize GST
  • E The monoclonal antibody of the present invention recognizes an ELDEWA epitope GST- ELDEWA (26KD) '.
  • ELDEWA is a unique epitope of HIV-1 virus type 0 strain. It can be used as a target site for the identification and diagnosis of HIV-1 virus type 0 strain, and can also be used as a target site for therapeutic drugs.
  • the monoclonal antibody of the present invention will be widely used in identifying and diagnosing HIV-1 virus type 0 strain and preparing passive immune drugs for infection of HIV-1 type 0 strain. Drugs using the monoclonal antibody of the present invention as an active ingredient can be widely used. Hope to be applied in the treatment of AIDS.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Microbiology (AREA)
  • Hematology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Communicable Diseases (AREA)
  • AIDS & HIV (AREA)
  • Oncology (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

La présente invention se rapporte à un nouvel épitope immunologique de la souche VIH de type O et ses utilisations. La terminaison N de l'épitope est une asparagine, sa terminaison C est constituée de résidus adjacents d'acide glutamique. La terminaison N de l'épitope est constituée de deux résidus d'acide aminés liés normalement avec le résidu de leucine. La terminaison C de l'épitope se lie normalement au résidu de tryptophane. La séquence d'acides aminés de l'épitope immunologique est LDEW. D'après la séquence, la terminaison N se lie normalement au résidu d'acide glutamique. La terminaison C se lie normalement au résidu l'alanine, de manière que la séquence d'acides aminés de l'épitope immunologique soit ELDEWA. L'épitope peut être utilisé comme cible pour l'identification et le diagnostic du VIH-1 de type O, et comme cible pour les médicaments.
PCT/CN2002/000552 2002-07-29 2002-08-09 Epitope immunologique de la souche vih type o et ses utilisations WO2004011490A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002325467A AU2002325467A1 (en) 2002-07-29 2002-08-09 A immounlogical epitope of the hiv strain type o and the uses thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CNA021253730A CN1472314A (zh) 2002-07-29 2002-07-29 艾滋病病毒o型株的一个免疫学表位及其应用
CN02125373.0 2002-07-29

Publications (1)

Publication Number Publication Date
WO2004011490A1 true WO2004011490A1 (fr) 2004-02-05

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2002/000552 WO2004011490A1 (fr) 2002-07-29 2002-08-09 Epitope immunologique de la souche vih type o et ses utilisations

Country Status (3)

Country Link
CN (1) CN1472314A (fr)
AU (1) AU2002325467A1 (fr)
WO (1) WO2004011490A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991013909A1 (fr) * 1990-03-15 1991-09-19 Proteus Molecular Design Limited Polypeptides synthetiques
EP0492560A2 (fr) * 1990-12-26 1992-07-01 Joseph P. Cotropia Anticorps monoclonaux humains contre la glycoprotéine transmembranaire (gp41) de HIV-1, et peptides associés
WO1994029339A1 (fr) * 1993-06-09 1994-12-22 Connaught Laboratories Limited Peptides synthetiques en tandem contre le vih-1

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991013909A1 (fr) * 1990-03-15 1991-09-19 Proteus Molecular Design Limited Polypeptides synthetiques
EP0492560A2 (fr) * 1990-12-26 1992-07-01 Joseph P. Cotropia Anticorps monoclonaux humains contre la glycoprotéine transmembranaire (gp41) de HIV-1, et peptides associés
WO1994029339A1 (fr) * 1993-06-09 1994-12-22 Connaught Laboratories Limited Peptides synthetiques en tandem contre le vih-1

Also Published As

Publication number Publication date
AU2002325467A1 (en) 2004-02-16
AU2002325467A8 (en) 2004-02-16
CN1472314A (zh) 2004-02-04

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