WO2004011490A1 - A immounlogical epitope of the hiv strain type o and the uses thereof - Google Patents
A immounlogical epitope of the hiv strain type o and the uses thereof Download PDFInfo
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- 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
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- Prior art keywords
- epitope
- hiv
- strain
- amino acid
- immunological epitope
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- 125000000539 amino acid group Chemical group 0.000 claims abstract description 12
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims abstract description 4
- 235000013922 glutamic acid Nutrition 0.000 claims abstract description 4
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- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 241001529936 Murinae Species 0.000 claims description 3
- 229940126585 therapeutic drug Drugs 0.000 claims description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 2
- 239000000427 antigen Substances 0.000 claims description 2
- 102000036639 antigens Human genes 0.000 claims description 2
- 108091007433 antigens Proteins 0.000 claims description 2
- 235000003704 aspartic acid Nutrition 0.000 claims description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 7
- 238000003745 diagnosis Methods 0.000 abstract description 3
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 abstract description 2
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 abstract 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 abstract 1
- 235000009582 asparagine Nutrition 0.000 abstract 1
- 229960001230 asparagine Drugs 0.000 abstract 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 abstract 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 abstract 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 abstract 1
- 101800001690 Transmembrane protein gp41 Proteins 0.000 description 6
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- 102000004169 proteins and genes Human genes 0.000 description 2
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- 229940033330 HIV vaccine Drugs 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000009352 congenital transmission Effects 0.000 description 1
- KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
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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)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mycology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Public Health (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- AIDS & HIV (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Communicable Diseases (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Description
Claims
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 (en) | 2002-07-29 | 2002-07-29 | Immunity expression of AIDS virus O and its use |
CN02125373.0 | 2002-07-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2004011490A1 true WO2004011490A1 (en) | 2004-02-05 |
Family
ID=30121235
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2002/000552 WO2004011490A1 (en) | 2002-07-29 | 2002-08-09 | A immounlogical epitope of the hiv strain type o and the uses thereof |
Country Status (3)
Country | Link |
---|---|
CN (1) | CN1472314A (en) |
AU (1) | AU2002325467A1 (en) |
WO (1) | WO2004011490A1 (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991013909A1 (en) * | 1990-03-15 | 1991-09-19 | Proteus Molecular Design Limited | Synthetic polypeptides |
EP0492560A2 (en) * | 1990-12-26 | 1992-07-01 | Joseph P. Cotropia | Human monoclonal antibodies directed against the transmembrane glycoprotein (gp41) of HIV-1, and related peptides |
WO1994029339A1 (en) * | 1993-06-09 | 1994-12-22 | Connaught Laboratories Limited | Tandem synthetic hiv-1 peptides |
-
2002
- 2002-07-29 CN CNA021253730A patent/CN1472314A/en active Pending
- 2002-08-09 AU AU2002325467A patent/AU2002325467A1/en not_active Abandoned
- 2002-08-09 WO PCT/CN2002/000552 patent/WO2004011490A1/en not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991013909A1 (en) * | 1990-03-15 | 1991-09-19 | Proteus Molecular Design Limited | Synthetic polypeptides |
EP0492560A2 (en) * | 1990-12-26 | 1992-07-01 | Joseph P. Cotropia | Human monoclonal antibodies directed against the transmembrane glycoprotein (gp41) of HIV-1, and related peptides |
WO1994029339A1 (en) * | 1993-06-09 | 1994-12-22 | Connaught Laboratories Limited | Tandem synthetic hiv-1 peptides |
Also Published As
Publication number | Publication date |
---|---|
AU2002325467A8 (en) | 2004-02-16 |
CN1472314A (en) | 2004-02-04 |
AU2002325467A1 (en) | 2004-02-16 |
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