CN1339320A - AIDS vacuum and its preparing method and use - Google Patents

AIDS vacuum and its preparing method and use Download PDF

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Publication number
CN1339320A
CN1339320A CN00123487A CN00123487A CN1339320A CN 1339320 A CN1339320 A CN 1339320A CN 00123487 A CN00123487 A CN 00123487A CN 00123487 A CN00123487 A CN 00123487A CN 1339320 A CN1339320 A CN 1339320A
Authority
CN
China
Prior art keywords
epitope
aids
vaccine
polypeptide
neutralizing
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.)
Pending
Application number
CN00123487A
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Chinese (zh)
Inventor
陈应华
丁健
陆韵
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.)
Tsinghua University
Original Assignee
Tsinghua 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
Application filed by Tsinghua University filed Critical Tsinghua University
Priority to CN00123487A priority Critical patent/CN1339320A/en
Priority to AU2002213755A priority patent/AU2002213755A1/en
Priority to PCT/CN2001/001190 priority patent/WO2002026253A1/en
Publication of CN1339320A publication Critical patent/CN1339320A/en
Pending legal-status Critical Current

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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

Abstract

The AIDS vaccine includes at least one conjugate epitope polypeptide formed through coupling to carrier protein or carrier polypeptide and the epitope polypeptide contains at least one epitope of neutralizing epitope and its variation epitopes of human immune deficiency virus membrane protein or contains at least once repeated epitope of neutralizing epitope and its variation epitopes of human immune deficiency virus membrane protein, its preparation includes the following basic steps: artificial synthesis of polypeptide; coupling the said polypeptide to carrier protein or carrier polypeptide; compounding with adjuvant to prepare vaccine. The vaccine may be used as the medicine for treating AIDS.

Description

A kind of AIDS vaccine and preparation method thereof and application
The present invention relates to vaccine and preparation method thereof and application, particularly relate to a kind of AIDS vaccine and preparation method thereof and application with biotechnology preparation.
Acquired immune deficiency syndrome (AIDS) claims acquired immune deficiency syndrome (AIDS) again, is a kind of immune disease that is caused by HIV (human immunodeficiency virus) (HIV).Because it is propagated rapidly, the disease death rate is high, and does not still have specific treatment at present, does not more have vaccine and can prevent, thereby the title of " century plague " is arranged.
Existingly be used for only deferrable period of disease and prolong patient's life of clinical anti-AIDS drug, and cost an arm and a leg, toxicity is big.The present inventor discovers that the epitope polypeptide of multi-epitope can be induced the specific neutralizing antibody of high titre, predefined, many neutralizing epitope, and this theory is made AIDS vaccine to research and had directive significance.Simultaneously, external anti-AIDS drug clinical research result proves, the mucosa that can suppress HIV-1 virus at neutralizing antibody (monoclonal antibody) being used in combination in passive immunotherapy of the several specific neutralizing epitopes on the HIV-1 memebrane protein gp160 infects and mother-to-baby transmission, and can remove HIV-1 virus (Nature Medicine 1999,5:204 in the blood; Nature Medicine 2000,6:200; Nature Medicine 1999,5:211), this shows that being used in combination of several neutralizing antibodies is a kind of effective acquired immune deficiency syndrome (AIDS) immunization therapy strategy.
The purpose of this invention is to provide a kind of effective AIDS vaccine.
Another object of the present invention provides a kind of method for preparing above-mentioned AIDS vaccine.
A further object of the present invention provides the application of above-mentioned AIDS vaccine in the medicine of production for treating acquired immune deficiency syndrome (AIDS).
For achieving the above object, the present invention takes following design: a kind of AIDS vaccine, it consists essentially of at least one and is coupled to the epitope polypeptide that forms coupling matter on carrier protein or the carrier polypeptide, described epitope polypeptide contains at least one epi-position in human immunodeficiency virus's memebrane protein neutralizing epitope and the variant epitope thereof, perhaps contains at least one and at least once multiple again epi-position in human immunodeficiency virus's memebrane protein neutralizing epitope and the variant epitope thereof.
Described human immunodeficiency virus's memebrane protein is gp160.
The amino acid residue sequence of described neutralizing epitope and variant epitope thereof can be selected from:
GPGRAFY
GPGQTFY
GPGQAWY
ELDKWA
ELEKWA
ELNKWA
ELDEWA
RILAVERYLKD
In order to induce strong immune response, also comprise acceptable medicinal adjuvant in the described vaccine.
A kind of method for preparing AIDS vaccine consists essentially of following steps:
(1), synthetic at least one contains at least one neutralizing epitope of human immunodeficiency virus's memebrane protein and the epitope polypeptide of variant epitope or at least once multiple at least one neutralizing epitope and variant epitope thereof thereof respectively;
(2), above-mentioned epitope polypeptide is coupled to respectively on carrier protein or the carrier polypeptide forms coupling matter;
(3), above-mentioned coupling matter is equipped with acceptable adjuvant and is prepared into AIDS vaccine.
Specifically, above-mentioned this prepares that human immunodeficiency virus's memebrane protein is gp160 in the method for AIDS vaccine, and the amino acid residue sequence of neutralizing epitope wherein and variant epitope thereof can be selected from:
GPGRAFY
GPGQTFY
GPGQAWY
ELDKWA
ELEKWA
ELNKWA
ELDEWA
RILAVERYLKD
A kind of medicine for the treatment of acquired immune deficiency syndrome (AIDS) is a main active by above-mentioned AIDS vaccine, is equipped with medicinal adjuvant and forms.
Theory (Immunology Today, 20:588-589, in December, 1999 of the epiposition vaccine that proposes at first according to the present inventor; Immunobiology, 201:323-331, in December, 1999; Scand.J.Immunology.2000,51:497-501; Int.Arch.Allergy Immunology, 2000,121:80-84), AIDS vaccine of the present invention is a kind of multiple vaccines that can stimulate human body HIV (human immunodeficiency virus) (Human Immunodeficiency Virus) to be produced multi-faceted antibody, even produce in HIV (human immunodeficiency virus) (Human Immunodeficiency Virus) under the situation of variation, injected in the human body of this vaccine and also had the virus that corresponding antibody is killed invasion, the antibody amount of generation is a 10-240 mg/ml serum.Simultaneously the effective ingredient of this vaccine be coupled on carrier protein or the carrier polypeptide form coupling matter include the neutralizing epitope on human immunodeficiency virus's memebrane protein gp160 or the epitope polypeptide of variant epitope, it is active that these epitope polypeptides do not have the heredity of HIV (human immunodeficiency virus) (Human Immunodeficiency Virus), do not have renaturation and bring out the possibility of acquired immune deficiency syndrome (AIDS).
Studies show that the antibody of AIDS virus resisting can reduce the carrying capacity of virus in treating AIDS, delay the carrying out of disease.The present invention creatively with multi-joint-epiposition vaccine, multi-epitope-epiposition vaccine and the resistance of HIV-1 different-epiposition vaccine is used for the treatment of acquired immune deficiency syndrome (AIDS), avirulence not only, and in the immunization therapy effect that improves acquired immune deficiency syndrome (AIDS), also can reduce the treating AIDS cost.
According to the present invention, can produce the vaccine of its respective type very soon according to the variation situation of HIV (human immunodeficiency virus) (Human Immunodeficiency Virus), need not test for a long time, reduce production costs.This technology will produce significant impact to world's preventive medicine research, and will bring huge economic benefit and social benefit.
The invention will be further described below in conjunction with non-limiting specific embodiment.
Embodiment one: prepare based on the single epi-position-epiposition vaccine of the acquired immune deficiency syndrome (AIDS) of the main neutralizing epitope of HIV-1 gp160:
1. synthetic is based on 1 epitope polypeptide of 1 main neutralizing epitope among the HIV-1 gp160.Its sequence is:
C-GPGRAFYGGPGRAFYGGPGRAFY
2. utilize MBS (m-maleimidobenzoyl-N-hydroxy succinimide ester) with above-mentioned epitope polypeptide and carrier protein BSA coupling connection;
3. coupling matter is equipped with aluminium adjuvant and is prepared into the single epi-position-epiposition vaccine of HIV-1.
Embodiment two: prepare based on the single epi-position of the acquired immune deficiency syndrome (AIDS) of the main neutralizing epitope of HIV-1 gp160-multi-joint-epiposition vaccine:
1. synthetic is based on 3 epitope polypeptides of the main neutralizing epitope of HIV-1 gp160.The sequence of these 3 epitope polypeptides is:
C-ELDKWAG?ELDKWAG?ELDKWAG?ELDKWA
C-GPGRAFYGGPGRAFYGGPGRAFY
C-RILAVERYLKDGRILAVERYLKD
2. utilize MBS (m-maleimidobenzoyl-N-hydroxy succinimide ester) respectively with above-mentioned epitope polypeptide and carrier protein BSA coupling connection;
3. be equipped with after 3 kinds of coupling matters being mixed aluminium adjuvant be prepared into HIV-1 multi-joint-epiposition vaccine, wherein, the addition of various coupling matters is adjusted by the variation probability in each site that the crowd's of being suitable for statistical procedures draws.
Embodiment three: prepare the acquired immune deficiency syndrome (AIDS) multi-epitope-epiposition vaccine based on the main neutralizing epitope of HIV-1 gp160:
1. synthetic is based on 1 multi-epitope-epitope polypeptide of the main neutralizing epitope of HIV-1 gp160, and its sequence is:
CGELDKWAGGPGRAFYG?ELDKWAGGPGRAFY
2. utilize glutaraldehyde with above-mentioned multi-epitope-epitope polypeptide and carrier protein bovine serum albumin coupling connection;
3. above-mentioned coupling matter is equipped with aluminium adjuvant and is prepared into HIV-1 multi-epitope-epiposition vaccine.
Embodiment four: the preparation based on the acquired immune deficiency syndrome (AIDS) of the main neutralizing epitope of HIV-1 gp160 multi-joint-multi-epitope-epiposition vaccine:
1. synthetic is based on 3 multi-epitope-epitope polypeptides of the main neutralizing epitope of HIV-1 gp160.The sequence of these 3 multi-epitope-epitope polypeptides is:
CELDKWAGGPGRAFYG?ELDKWAGGPGRAFY
CGPGRAFYGELDKWAGRILAVERYLKD
CGPGRAFYGRILAVERYLKDGGPGRAFY
2. utilize glutaraldehyde that above-mentioned 3 multi-epitope-epitope polypeptides are joined with carrier protein bovine serum albumin coupling respectively;
3. 3 kinds of coupling matters are equipped with aluminium adjuvant respectively and are prepared into HIV-1 multi-epitope-epiposition vaccine, wherein, the addition of various coupling matters is adjusted by the variation probability in each site that the statistical procedures that is suitable for the crowd draws.
Embodiment five: the preparation based on the main neutralizing epitope of HIV-1 gp160 and the variation neutralizing epitope the acquired immune deficiency syndrome (AIDS) resistance different-multi-joint-epiposition vaccine:
1. synthetic is based on the variant epitope-epitope polypeptide of main neutralizing epitope of HIV-1 gp160 and variation neutralizing epitope, and the sequence of these variant epitope-epitope polypeptides is:
CELDKWAGELDKWAGELDKWAGELDKWA
CELEKWAGELEKWAGELEKWAGELEKWA
CELDEWAGELDEWAGELDEWAGELDEWA
CELNKWAGELNKWAGELNKWAGELNKWA
CGPGQTFYGGPGQTFYGGPGQTFY
CGPGQAWYGGPGQAWYGGPGQAWY
CGPGQAWYGELNKWAGGPGQAWYGELNKWA
2. utilize MBS (m-maleimidobenzoyl-N-hydroxy succinmide ester) that these variant epitope-epitope polypeptides are joined with carrier protein BSA coupling respectively;
3. be equipped with after above-mentioned coupling matter being mixed aluminium adjuvant be prepared into the HIV-1 resistance different-epiposition vaccine, wherein, the addition of various coupling matters is adjusted by the variation probability in each site that the crowd's of being suitable for statistical procedures draws.
Anti-AIDS vaccine in the various embodiments described above can be used as the primary activity composition of preparation treatment AIDS-treating medicine, when the vaccine with the various embodiments described above is used as the medicine of treatment acquired immune deficiency syndrome (AIDS), can according to circumstances be equipped with suitable adjuvant, concrete consumption can be adjusted according to the situation of different people.

Claims (10)

1, a kind of AIDS vaccine, it consists essentially of at least one and is coupled to the epitope polypeptide that forms coupling matter on carrier protein or the carrier polypeptide, described epitope polypeptide contains at least one epi-position in human immunodeficiency virus's memebrane protein neutralizing epitope and the variant epitope thereof, perhaps contains at least one and at least once multiple again epi-position in human immunodeficiency virus's memebrane protein neutralizing epitope and the variant epitope thereof.
2, a kind of AIDS vaccine according to claim 1 is characterized in that: described human immunodeficiency virus's memebrane protein is gp160.
3, a kind of AIDS vaccine according to claim 1 and 2, it is characterized in that: the amino acid residue sequence of described neutralizing epitope and variant epitope thereof is selected from:
GPGRAFY
GPGQTFY
GPGQAWY
ELDKWA
ELEKWA
ELNKWA
ELDEWA
RILAVERYLKD
4, a kind of AIDS vaccine according to claim 1 and 2 is characterized in that: also comprise acceptable medicinal adjuvant in the described vaccine.
5, a kind of AIDS vaccine according to claim 3 is characterized in that: also comprise acceptable medicinal adjuvant in the described vaccine.
6, a kind of method for preparing AIDS vaccine consists essentially of following steps:
(1), synthetic at least one contains at least one neutralizing epitope of human immunodeficiency virus's memebrane protein and the epitope polypeptide of variant epitope or at least once multiple at least one neutralizing epitope and variant epitope thereof thereof respectively;
(2), above-mentioned epitope polypeptide is coupled to respectively on carrier protein or the carrier polypeptide forms coupling matter;
(3), above-mentioned coupling matter is equipped with acceptable adjuvant and is prepared into AIDS vaccine.
7, according to claim 6 method for preparing AIDS vaccine, it is characterized in that: described human immunodeficiency virus's memebrane protein is gp160.
8, according to claim 6 or 7 one kind of method for preparing AIDS vaccine, it is characterized in that: the amino acid residue sequence of described neutralizing epitope and variant epitope thereof is selected from:
GPGRAFY
GPGQTFY
GPGQAWY
ELDKWA
ELEKWA
ELNKWA
ELDEWA
RILAVERYLKD
9, a kind of medicine for the treatment of acquired immune deficiency syndrome (AIDS) is a main active by any material in claim 1 or 2, is equipped with medicinal adjuvant and forms.
10, a kind of medicine for the treatment of acquired immune deficiency syndrome (AIDS) is a main active by any material in the claim 3, is equipped with medicinal adjuvant and forms.
CN00123487A 2000-08-18 2000-08-18 AIDS vacuum and its preparing method and use Pending CN1339320A (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CN00123487A CN1339320A (en) 2000-08-18 2000-08-18 AIDS vacuum and its preparing method and use
AU2002213755A AU2002213755A1 (en) 2000-08-18 2001-07-20 A vaccine for acids and its preparation and use
PCT/CN2001/001190 WO2002026253A1 (en) 2000-08-18 2001-07-20 A vaccine for acids and its preparation and use

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN00123487A CN1339320A (en) 2000-08-18 2000-08-18 AIDS vacuum and its preparing method and use

Publications (1)

Publication Number Publication Date
CN1339320A true CN1339320A (en) 2002-03-13

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AU (1) AU2002213755A1 (en)
WO (1) WO2002026253A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101914143A (en) * 2010-08-19 2010-12-15 清华大学 HIV-1 membrane fusion inhibitor and application thereof
CN1954217B (en) * 2004-02-06 2013-05-08 国立健康与医学研究所 A polypeptide derived from gp41, a vaccine composition comprising said polypeptide, and uses for treating an infection by an HIV virus in an individual

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102004005186B3 (en) * 2004-02-02 2005-10-13 Krka Tovarna Zdravil, D.D. Process for the preparation of purified ciprofloxacin

Family Cites Families (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
FR2671554A1 (en) * 1991-01-11 1992-07-17 Clonatec Sa HEPATITIS B VIRUS-BASED HBC ANTIGEN SYNTHETIC PEPTIDES, THEIR USE IN THE DETECTION OF VIRUS INFECTION AND VACCINATION AGAINST HEPATITIS B.
IT1254360B (en) * 1992-05-11 1995-09-14 San Romanello Centro Fond IMMUNOLOGICALLY HOMOLOGICAL EPITOPES OF HLA AND VIRUS HIV PROTEINS.
WO1995005851A1 (en) * 1993-08-20 1995-03-02 St. Luke's-Roosevelt Hospital Center HIV vif-RELATED COMPOSITIONS, AND PROPHYLACTIC AND THERAPEUTIC USES THEREOF
US7018637B2 (en) * 1998-02-23 2006-03-28 Aventis Pasteur, Inc Multi-oligosaccharide glycoconjugate bacterial meningitis vaccines

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1954217B (en) * 2004-02-06 2013-05-08 国立健康与医学研究所 A polypeptide derived from gp41, a vaccine composition comprising said polypeptide, and uses for treating an infection by an HIV virus in an individual
CN101914143A (en) * 2010-08-19 2010-12-15 清华大学 HIV-1 membrane fusion inhibitor and application thereof

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Publication number Publication date
WO2002026253A1 (en) 2002-04-04
AU2002213755A1 (en) 2002-04-08

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