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WO2002026253A1 - Vaccin contre le sida, son procede de preparation et ses applications - Google Patents

Vaccin contre le sida, son procede de preparation et ses applications Download PDF

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Publication number
WO2002026253A1
WO2002026253A1 PCT/CN2001/001190 CN0101190W WO0226253A1 WO 2002026253 A1 WO2002026253 A1 WO 2002026253A1 CN 0101190 W CN0101190 W CN 0101190W WO 0226253 A1 WO0226253 A1 WO 0226253A1
Authority
WO
WIPO (PCT)
Prior art keywords
epitope
aids
variant
polypeptide
vaccine
Prior art date
Application number
PCT/CN2001/001190
Other languages
English (en)
Chinese (zh)
Inventor
Yinghua Chen
Jian Ding
Yun Lu
Original Assignee
Tsinghua University
Jiangxi Dragon-Fiy Science And Tehnology Co. Ltd.
Beijing Guoxiweiye High Technology Development 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, Jiangxi Dragon-Fiy Science And Tehnology Co. Ltd., Beijing Guoxiweiye High Technology Development Co. Ltd filed Critical Tsinghua University
Priority to AU2002213755A priority Critical patent/AU2002213755A1/en
Publication of WO2002026253A1 publication Critical patent/WO2002026253A1/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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • 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
    • C12N2740/16022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Definitions

  • the invention relates to a vaccine prepared by bioengineering technology, a preparation method and application thereof, and particularly to an AIDS vaccine, a preparation method and application thereof.
  • HIV-1 human immunodeficiency virus
  • the inventors of the present invention have found that the multi-epitope epitope polypeptide can induce high-titer, pre-defined, multi-neutralizing epitope-specific neutralizing antibodies, and the theory has guiding significance for the research and manufacture of AIDS vaccines.
  • the object of the present invention is to provide an effective vaccine for preventing AIDS.
  • Another object of the present invention is to provide a method for preparing the aforementioned AIDS vaccine.
  • Another object of the present invention is to provide the application of the above-mentioned AIDS vaccine in the production of a medicament for treating AIDS.
  • An AIDS vaccine which basically includes at least one epitope polypeptide coupled to a carrier protein or a carrier polypeptide to form a conjugate, the epitope polypeptide containing human immunodeficiency At least one epitope of the virus membrane protein neutralizing epitope and its variant epitope, or an epitope containing at least one of the human immunodeficiency virus membrane protein neutralizing epitope and its variant epitope and repeating at least once, or Contains at least one of the CTL epitope of the HIV-1 viral protein and its variant epitopes.
  • the human immunodeficiency virus proteins are gpl60, Nef, RT, Vif.
  • amino acid residue sequence of the neutralizing epitope and its variant epitope may be selected from:
  • acceptable pharmaceutically acceptable adjuvants are also included in the vaccine.
  • a method for preparing an AIDS vaccine basically includes the following steps:
  • the human immunodeficiency virus membrane protein is gpl60, and the amino acid residue sequence of the neutralizing epitope and its variant epitope may be selected from:
  • the AIDS vaccine of the present invention is a multiple vaccine that can stimulate the human body to produce multi-directional antibodies and CTL responses to HIV. Even in the case of HIV mutation, there will be corresponding antibodies in people who have injected the vaccine.
  • the active ingredient of the vaccine is a table containing a neutralizing epitope or a variant epitope on a human immunodeficiency virus protein gpl60, Nef, RT, Vif coupled to a carrier protein or carrier polypeptide to form a conjugate.
  • Peptides, these epitope polypeptides do not have the genetic activity of HIV, there is no possibility of renaturation and induction of AIDS.
  • Example 1 Preparation of HIV single epitope-epitope vaccine based on HIV-1 gpl60 primary neutralizing epitope:
  • MBS CsmBleimidobenzoyl-N-hydroxy succinimide ester was used to couple the epitope polypeptide with the carrier protein BSA;
  • Example 2 Preparation of a single epitope, multiple epitope vaccine for HIV based on HIV-1 gpl60 main neutralizing epitope:
  • the HIV-1 polytope vaccine was prepared by mixing three kinds of conjugates with aluminum adjuvant, wherein the amount of each conjugate was determined by the statistical analysis of the applicable population. The probability of mutation is adjusted.
  • Example 3 Preparation of HIV multi-epitope-epitope vaccine based on HIV-1 gpl60 main neutralizing epitope:
  • Example 4 Preparation of an HIV-1 multiple epitope-epitope vaccine based on the HIV-1 gpl60 primary neutralizing epitope:
  • Example 5 Preparation of HIV anti-variant-multiple-one epitope vaccine based on HIV-1 gpl60 main neutralizing epitope and variant neutralizing epitope:
  • conjugates are mixed with aluminum adjuvant to prepare an HIV-1 anti-variation-epitope vaccine, wherein the amount of each conjugate added is the variation of each point obtained by statistical processing of the applicable population. Chance to adjust.
  • Example 6 Preparation of a multiple epitope vaccine based on the HIV-1 CTL epitope: 1. Synthetic epitope polypeptide containing HIV-1 CTL epitope. Its sequence is:
  • the HIV-1 polytope vaccine is prepared by mixing the conjugates with aluminum adjuvant, wherein the amount of each conjugate is determined by the mutation probability of each point obtained from the statistical processing of the applicable population. Adjustment.
  • Example 7 Preparation of HIV multi-epitope primary antibody variant-epitope vaccine based on HIV-1 neutralizing epitopes and CTL epitopes and their variant epitopes:
  • CELDKWAGVIYQYMDDCG ELDKWAGVIYQYMDDC CGPGRAFYGGLEGIYYSARGRILAVERYLKD CGLEGIYYSARGRILAVERYLKDGGPGRAFY CGPGRAFYGGPGQTFYGGPGQAWY CELDKWAGELEKWAGELNKWAGELDEWA CRILAVERYLKDGGLEGIYMDDCY
  • MBS was used to couple the above five epitope polypeptides to the carrier protein bovine serum albumin respectively.
  • Three kinds of conjugates were prepared with aluminum adjuvants to prepare HIV-1 multi-epitope primary antibody variants and epitopes. For vaccines, the amount of various conjugates added is adjusted by the mutation probability of each point obtained from the statistical processing of the applicable population.
  • the present invention creatively uses the HIV-1 multi-epitope-epitope vaccine, multi-epitope-epitope vaccine and multi-epitope-antibody variant-epitope vaccine for the prevention and treatment of AIDS, which is not only non-toxic, but also improves AIDS. Prevention and treatment effects.
  • the corresponding type of vaccine can be quickly produced according to the variation of the HIV virus, without the need for long-term tests, and the production cost can be reduced.
  • This technology will have a significant impact on the world's preventive medicine research and will bring huge economic and social benefits.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • AIDS & HIV (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Genetics & Genomics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un vaccin contre le SIDA, son procédé de préparation et ses applications. Ledit vaccin renferme essentiellement au moins un polypeptide épitope conjugué à une protéine porteuse ou à un polypeptide porteur de manière à former des conjugués. Ledit polypeptide épitope contient un épitope de neutralisation de la protéine du virus de l'immunodéficience humaine et au moins un épitope provenant d'une de ses variantes ou un épitope de neutralisation de la protéine de l'immunodéficience humaine et au moins un épitope dupliqué une fois au minimum ou encore un épitope de la protéine de l'immunodéficience humaine et ses variantes. Le procédé de préparation du vaccin de cette invention consiste à 1) synthétiser de manière artificielle des polypeptides; 2) combiner ledit polypeptide au vecteur afin de former des conjugués distincts; 3) formuler un vaccin en combinant lesdits conjugués à l'aide d'un adjuvant. Ce vaccin peut servir de médicament à action préventive et thérapeutique contre le SIDA.
PCT/CN2001/001190 2000-08-18 2001-07-20 Vaccin contre le sida, son procede de preparation et ses applications WO2002026253A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002213755A AU2002213755A1 (en) 2000-08-18 2001-07-20 A vaccine for acids and its preparation and use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN00123487A CN1339320A (zh) 2000-08-18 2000-08-18 一种艾滋病疫苗及其制备方法与应用
CN00123487.0 2000-08-18

Publications (1)

Publication Number Publication Date
WO2002026253A1 true WO2002026253A1 (fr) 2002-04-04

Family

ID=4589907

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2001/001190 WO2002026253A1 (fr) 2000-08-18 2001-07-20 Vaccin contre le sida, son procede de preparation et ses applications

Country Status (3)

Country Link
CN (1) CN1339320A (fr)
AU (1) AU2002213755A1 (fr)
WO (1) WO2002026253A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102004005186B3 (de) * 2004-02-02 2005-10-13 Krka Tovarna Zdravil, D.D. Verfahren zur Herstellung von gereinigtem Ciprofloxacin

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005076001A2 (fr) * 2004-02-06 2005-08-18 Inserm (Institut National De La Sante Et De La Recherche Medicale) Polypeptide derive de gp41, composition de vaccin comprenant ce polypeptide et utilisations de celle-ci pour traiter une personne infectee par un virus vih
CN101914143A (zh) * 2010-08-19 2010-12-15 清华大学 Hiv-1病毒膜融合抑制剂及其应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5013548A (en) * 1987-09-08 1991-05-07 Duke University Production of antibodies to HIV
EP0494825A1 (fr) * 1991-01-11 1992-07-15 Clonatec S.A. Peptides synthétiques dérivant de l'antigène HBc du virus de l'hépatite B
WO1993023427A1 (fr) * 1992-05-11 1993-11-25 Fondazione Centro San Romanello Del Monte Tabor Epitopes de proteines de vih homologues, sur un plan immonologique, des hla
WO1995005851A1 (fr) * 1993-08-20 1995-03-02 St. Luke's-Roosevelt Hospital Center Compositions relatives au facteur viral infectieux de hiv, utilisations prophylactiques et therapeutiques
WO1999042130A1 (fr) * 1998-02-23 1999-08-26 Connaught Laboratories Limited Vaccins anti-meningite bacterienne, a base de glycoconjugue d'oligosaccharides multiples

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5013548A (en) * 1987-09-08 1991-05-07 Duke University Production of antibodies to HIV
EP0494825A1 (fr) * 1991-01-11 1992-07-15 Clonatec S.A. Peptides synthétiques dérivant de l'antigène HBc du virus de l'hépatite B
WO1993023427A1 (fr) * 1992-05-11 1993-11-25 Fondazione Centro San Romanello Del Monte Tabor Epitopes de proteines de vih homologues, sur un plan immonologique, des hla
WO1995005851A1 (fr) * 1993-08-20 1995-03-02 St. Luke's-Roosevelt Hospital Center Compositions relatives au facteur viral infectieux de hiv, utilisations prophylactiques et therapeutiques
WO1999042130A1 (fr) * 1998-02-23 1999-08-26 Connaught Laboratories Limited Vaccins anti-meningite bacterienne, a base de glycoconjugue d'oligosaccharides multiples

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102004005186B3 (de) * 2004-02-02 2005-10-13 Krka Tovarna Zdravil, D.D. Verfahren zur Herstellung von gereinigtem Ciprofloxacin

Also Published As

Publication number Publication date
AU2002213755A1 (en) 2002-04-08
CN1339320A (zh) 2002-03-13

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