JPH05502442A - Peptides containing the CTL epitope of HIV protein and their use - Google Patents
Peptides containing the CTL epitope of HIV protein and their useInfo
- Publication number
- JPH05502442A JPH05502442A JP2513793A JP51379390A JPH05502442A JP H05502442 A JPH05502442 A JP H05502442A JP 2513793 A JP2513793 A JP 2513793A JP 51379390 A JP51379390 A JP 51379390A JP H05502442 A JPH05502442 A JP H05502442A
- Authority
- JP
- Japan
- Prior art keywords
- peptide fragment
- ctl
- protein
- hiv
- peptide
- 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
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 33
- 108090000623 proteins and genes Proteins 0.000 title claims description 20
- 102000004169 proteins and genes Human genes 0.000 title claims description 18
- 102000004196 processed proteins & peptides Human genes 0.000 title description 14
- 102000007079 Peptide Fragments Human genes 0.000 claims description 51
- 108010033276 Peptide Fragments Proteins 0.000 claims description 51
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 22
- 210000004027 cell Anatomy 0.000 claims description 17
- 241001465754 Metazoa Species 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 16
- 150000001413 amino acids Chemical class 0.000 claims description 13
- 230000004044 response Effects 0.000 claims description 13
- 101710192141 Protein Nef Proteins 0.000 claims description 11
- 125000000539 amino acid group Chemical group 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 8
- 102100034353 Integrase Human genes 0.000 claims description 7
- 108010078428 env Gene Products Proteins 0.000 claims description 7
- 101710177291 Gag polyprotein Proteins 0.000 claims description 6
- 101710125418 Major capsid protein Proteins 0.000 claims description 6
- 239000012634 fragment Substances 0.000 claims description 6
- 238000012360 testing method Methods 0.000 claims description 6
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 claims description 5
- 241000700605 Viruses Species 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 210000004698 lymphocyte Anatomy 0.000 claims description 3
- 230000001737 promoting effect Effects 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims 3
- 235000018102 proteins Nutrition 0.000 description 15
- 229940024606 amino acid Drugs 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 7
- 238000003556 assay Methods 0.000 description 5
- 241000700618 Vaccinia virus Species 0.000 description 4
- -1 p-methylbenzyl group Chemical group 0.000 description 4
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 241000238557 Decapoda Species 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 3
- 229910052804 chromium Inorganic materials 0.000 description 3
- 239000011651 chromium Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241001669573 Galeorhinus galeus Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical class C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 229940033330 HIV vaccine Drugs 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 101900209501 Vaccinia virus Thymidine kinase Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000003855 acyl compounds Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000007402 cytotoxic response Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
-
- 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
- C12N2740/16211—Human Immunodeficiency Virus, HIV concerning HIV gagpol
- C12N2740/16222—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
- C12N2740/16311—Human Immunodeficiency Virus, HIV concerning HIV regulatory proteins
- C12N2740/16322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
(57)【要約】本公報は電子出願前の出願データであるため要約のデータは記録されません。 (57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】 ＨＩＶ蛋白質のＣＴＬ−エピトープを含むペプチド類とその利用 この発明は、細胞毒性リンパ球（以下、ｒ ＣＴ Ｌ Ｊと略記する）工と１・ −ブを含有するペプチドに関し、特に人体免疫不全ウィルス（以下、ｒＨＩＶＪ と略記する）タンパク質、およびＣＴＬエピトープを含有するペプチド断片とそ の用途に関する。これらのペプチドあるいは誘導体は、ＣＴＬ応答を誘導あるい は促進するために使用することができる。[Detailed description of the invention] Peptides containing CTL-epitope of HIV protein and their use This invention relates to cytotoxic lymphocyte (hereinafter abbreviated as rCTLJ) technology and 1. In particular, human immunodeficiency virus (hereinafter referred to as rHIVJ) (abbreviated as ), and peptide fragments containing CTL epitopes and their Concerning the use of. These peptides or derivatives induce or induce CTL responses. can be used to promote.
ウィルス感染の細胞媒介性免疫（以下、ｒＣＭ’ＩＪと略記するとする）は、ウ ィルス感染に対する宿主防衛と想定されている。このＣＭ工は、ＨＩＶあるいは エイズウィルスに対する有効なワクチンの開発において重要視されている。それ は、ＨＩＶワクチンあるいは治療法が必ずしも合理的な予防方法ではなかったか らである。そこでその後は、前記ＨＩＶに対するＣＭＩ応答の誘導、ならびに前 記ＣＴＬ応答を刺激するＨ ｉ Ｖタンパク質の特殊なエピトープの特定のガロ へと、次第に関心が移行されて来た。Cell-mediated immunity to viral infection (hereinafter abbreviated as rCM'IJ) is It is assumed to be a host defense against virus infection. This commercial worker is HIV or It is considered important in the development of an effective vaccine against the AIDS virus. that Are HIV vaccines or treatments not necessarily a reasonable method of prevention? It is et al. Therefore, after that, the induction of the CMI response against the HIV, as well as the specific galvanotopes of specific epitopes of H i V proteins that stimulate CTL responses. Interest gradually shifted to this.
この発明は、まず第一に、ＨＩＶタンパク質によって誘発されるＣＴＬ、あるい はそのＣＴＬエピトープによって認識されるところのエピトープを含有するペプ チド断片を提供する。This invention first focuses on CTL induced by HIV protein or is a peptide containing the epitope recognized by the CTL epitope. Providing chido fragments.
さらに好ましくは、前記ペプチド断片が、ＮＥＦ、ＧＡＧ、あるいはＥＮＶタン パク質によって誘発されるＣＴＬ、またはそれらのＣＴＬエビ）・−プによって 認識されるペプチド断片である。More preferably, the peptide fragment is NEF, GAG, or ENV protein. protein-induced CTLs, or those CTL shrimp). It is a recognized peptide fragment.
この発明において「ペプチド断片」とは、ＣＴＬエピトープを含む従来のタンパ ク質の有するアミノ酸基よりも少数のアミノ酸基を有するペプチドを意味する。In this invention, "peptide fragment" refers to a conventional protein fragment containing a CTL epitope. This refers to a peptide that has fewer amino acid groups than that of a protein.
１個のエピトープを含むペプチド断片で、そのエピトープがＩ−（Ｉ Ｖタンパ ク質によって誘発されたＣＴＬによって認識されるものも、この発明ではＣＴＬ エピトープを含むペプチド断片と称する。A peptide fragment containing one epitope, which epitope is I-(IV protein). What is recognized by CTLs induced by CTLs is also recognized by CTLs in this invention. It is called a peptide fragment containing an epitope.
これらのペプチド断片は、従来存在するタンパク質またはそれらのＣＴ Ｌエピ トープによって誘発されたＣＴＬがこれを認識するのであれば、従来のタンパク 質の断片、またはその類似体であってもよい。These peptide fragments are derived from conventional proteins or their CTL epitopes. If the CTL induced by the tope recognizes this, the conventional protein or an analog thereof.
これらのペプチド断片は、ＣＴＬエピトープを形成するアミノ酸基のみによって 構成されていても、また追加のアミノ酸基が含まれていてもよい、但し、断片の アミノ酸基の数は従来のものよりも少ない。These peptide fragments are separated by only the amino acid groups that form the CTL epitope. or may contain additional amino acid groups, provided that the fragment The number of amino acid groups is smaller than conventional ones.
一実施例においては、１個のエピトープを含むペプチド断片が得られ、このエピ トープはＨＩＶ−１のＮＥＦタンパク質によって誘起されたＣＴＬによって認識 される。１個のＣＴ Ｌエピトープを含むペプチド断片で、このエピトープがＮ ＥＦタンパク質によって誘起されたＣ Ｔ Ｌによって認識されるものは、この ようなＣＴＬエピトープまたはその類似体あるいは誘導体を含ｒ、、ｙＮＥＦタ ンパク質の断片であってもよい。ＮＥＦタンパク質のＣＴＬエピトープは、ＮＥ Ｆタンパク質のアミノ酸基の７３〜９７番目に含まれることが、Ｌａｓ Ａ１ａ 厘ｏｓ のＮａｔｉｏｎａｌＬａｂｏｒａｔｏｒｙ のＨＩＶ配列データベース で次のように示されている（単文字アミノ酸コードである）。In one example, a peptide fragment containing one epitope is obtained; The tope is recognized by CTLs induced by the NEF protein of HIV-1. be done. A peptide fragment containing one CT L epitope, and this epitope is N What is recognized by CTL induced by EF protein is this containing a CTL epitope or an analog or derivative thereof such as It may also be a protein fragment. The CTL epitope of the NEF protein is NE Las A1a is included in the 73rd to 97th amino acid groups of F protein. National Laboratory’s HIV sequence database It is shown as follows (single letter amino acid code).
ＱＶＰＬＲＰＭＴｆＹカＦ、Ｙ ノ方；６’好適） ＫＡＡＶＤＬＳＩ（ＦＬＫ ＥＫＧＧＩ−さらに具体的には、このようなＣＴＬエピトープは、（ＬｏｓＡ、 １ａｍｏｓ 配列）の７３〜９７番目の塩基によって構成され、その構造は次の ように定義される。QVPLRPMTfY (F, Y direction; 6' suitable) KAAVDLSI (FLK EKGGI - More specifically, such CTL epitopes include (LosA, 1amos sequence), and its structure is as follows: It is defined as follows.
ＱＶＰＬＲＰＭＴ （ＹかＦ、Ｙが好適）Ｋこの発明の他の見地では、１個のエ ピトープを含むペプチド断片で、ぞのエピトープがＨＩＶタンパク質によって誘 起されたＣＴＬによって認識されるものは、ＨＴＶ感染の判定のための検定に利 用できることである。QVPLRPMT (Y or F, Y is preferred) K In another aspect of this invention, one A peptide fragment containing a pitope, in which the epitope is induced by HIV protein. Those recognized by the generated CTLs can be used in assays for determining HTV infection. It is something that can be used.
この発明のさらに他の見地では、ＣＴ Ｌ反応を促進させる方法が提供される。In yet another aspect of the invention, a method of promoting CTL reactions is provided.
このＣＴＬ反応は、ｌ−１ＩＶに感染した動物から得た末梢血リンパ球を、ＣＴ Ｌエピトープを含むペプチド断片と接触させるものである。このペプチド断片は 、ＮＥＦタンパク質のＣＴＬエピトープ、Ｇ Ａ、 Ｇタンパク質のＣＴＬエビ ］・−ブ、あるいはＥＮＶタンパク質のＣＴＬを含んでいることが望ましい、こ のＣＴＬ反応は試験管内で生起させることもできる。試験管内で促進させるため には、血清反応陽性の個人から得た末梢血単核球（ＰＢＭＣ）と、前記の型のペ プチドを培養すればよい。This CTL reaction allows peripheral blood lymphocytes obtained from l-1IV-infected animals to be It is brought into contact with a peptide fragment containing the L epitope. This peptide fragment is , CTL epitope of NEF protein, G A, CTL shrimp of G protein ]・-bu or ENV protein CTL. CTL reactions can also occur in vitro. To promote in vitro Peripheral blood mononuclear cells (PBMCs) obtained from seropositive individuals and All you have to do is cultivate putido.
前記ＣＴＬは生体内でも誘起することができる。そのためには、ＨＩＶに感染し た動物に、前記の型のＣＴＬエビ）・−ブを有するペプチド断片を投与すればよ い。さらに具体的には、前記ＨＩ Ｖに対するＣＴＬ部位を含む構築体（例えば Ｎｅｆ７Ｄ）によって免疫することによって、ＣＴＬを生体内で生起させること ができる。これらのワクチン類は、ＣＴＬ反応を生起させるための伝播体や助成 体を使用した標準的な手法によって調製することができる。さらに１個のエピト ープを有するペプチドまたはペプチド誘導体を合成することもでき、また化学的 に修飾して外因性のアミノ酸や脂肪酸、または疏水性部分を含むようにし、それ によってＣＴ Ｌ反応の誘起または促進を図る。１＠のＣＴ Ｌエピトープを有 するペプチドまたはペプチド誘導体の修飾方法は、ネイチャー等に掲載されてい る。The CTL can also be induced in vivo. To do this, you must be infected with HIV. A peptide fragment containing the above-mentioned type of CTL shrimp) may be administered to a given animal. stomach. More specifically, a construct containing a CTL site for the above-mentioned HIV (e.g. Generating CTL in vivo by immunizing with Nef7D) Can be done. These vaccines require carriers and aids to generate a CTL response. It can be prepared by standard techniques using the body. 1 more epitome It is also possible to synthesize peptides or peptide derivatives with be modified to contain exogenous amino acids, fatty acids, or hydrophobic moieties; The aim is to induce or promote the CTL reaction. 1@ CT L epitope Methods for modifying peptides or peptide derivatives are published in Nature, etc. Ru.
使用量および投与計画は、標準ワクチン化実施法により、最適なものとすること ができる。平均的な成人に対する有効用量は、１．０ないし１５００マイクログ ラムの範囲にあるものと想定される。The dosage and dosing schedule should be optimized using standard vaccination practices. Can be done. Effective doses for the average adult range from 1.0 to 1500 micrograms. It is assumed that it is in the range of Ram.
以下、）＝の発明を実施例に基づいて詳細に説明する。Hereinafter, the invention of )= will be explained in detail based on examples.
実施例Ｉ Ｃａ＞組換えワクシニアウィルスの構築ｎｅｆのコード配列は、Ｖｅｎｋａｔｅ ｓａｎ博士よりｃＤＮＡクローンとして入手した。このｃＤＮＡはＨＩ Ｖの単 離株Ｎ Ｌ ４３２ （Ａ ｄ ａ ｃ ｈ、 １他）由来であった。標準的な 組換えＤＮＡ技法を用いて、ｎ、 ｅ ｆ遺伝子を切り出し、ワクシニアウィル ス統合ベクターにはＰ７．５という用語で表わされるワクシニアウィルスのプロ モータが含まれており、これにより外来遺伝子が感染後遅かれ早かれ発現するこ とが可能になるａｎｅｆのコード配列はＰ７．５の下方に配置した。このＰ７． ５ｎｅｆカセツトをａｌ準的な手順でワクシニアウィルスのチミジンキナーゼ（ Ｔ Ｋ、 ）の部位に挿入したところ、ＴＫによる不活化が発生した。ＴＫ組換 えワクシニアウィルスをｖＴＦｎｅｆと命名し、これを単離、精製した。ｖＴＦ ｎ、ｅｆを用いた発現試験を実施し、Ｎｅｆが適切に発現されることをｉ認した 。放射線標識を施したアミノ酸の存在下で、単層細胞にｖＴＦｎｅｆを感染させ た。細胞の融解物をｎ、 ｅ ｆ抗血清を用いて免疫学的に沈澱させた。特異的 な２７ｋＤ （キロダルトン）タンパク質は予想されたｎ、 ｅ ｆ分子の大き さと一致し、また以前に報告されたその値とも一致した。またｎｅｆはミリスチ ン酸塩となり、ｎｅｆのコード配列を正しく発現していることが判った。Example I Construction of recombinant vaccinia virus The coding sequence of nef was It was obtained as a cDNA clone from Dr. This cDNA is a single HI V It was derived from isolated strain NL 432 (A d a c h, 1, etc.). Standard Using recombinant DNA technology, the n and ef genes were excised and transformed into vaccinia virus. The integrated vector contains a vaccinia virus protein designated by the term P7.5. contains a motor that allows foreign genes to be expressed sooner or later after infection. The coding sequence of anef that enables this is located below P7.5. This P7. The 5nef cassette was injected into vaccinia virus thymidine kinase ( When inserted into the site of TK, ), inactivation by TK occurred. TK recombination The vaccinia virus was named vTFnef and was isolated and purified. vTF We conducted an expression test using n and ef and found that Nef was appropriately expressed. . Infect monolayers of cells with vTFnef in the presence of radiolabeled amino acids. Ta. Cell lysates were immunoprecipitated using n, e f antisera. Specific The 27 kD (kilodalton) protein has the predicted molecular size of n, e, and the previously reported values. Also, nef is miristi It was found that the nef coding sequence was correctly expressed.
（ｂ）ｎ、ｅｆ特異性ＣＴＬ応答による個体の識別組換えウィルスｖ Ｔ Ｆ ｎ、 ｅ ｆを使用して、循環血中のＴリンパ球がｎ、 ｅ ｆに対して示すＣ ＴＬ活性について検査した。対象はＨＩＶ−１患者で健康な１２名とした。これ らの患者から新鮮な末梢血単核球（ＰＢＭＣ’）を採取し、ｖＴＦｎｅｆを感染 させた自己の細胞に対する細胞融解活性について調べた。(b) Identification of individuals by n, ef-specific CTL response Recombinant virus v TF Using n, e f, the C that T lymphocytes in the circulating blood exhibit for n, e f Tested for TL activity. The subjects were 12 healthy HIV-1 patients. this Fresh peripheral blood mononuclear cells (PBMC') were collected from these patients and infected with vTFnef. The cytolytic activity against autologous cells was investigated.
分画化していないＰＢＭＣを１（ｙｐａｑｕｅ／Ｆ ｉ ｃｏ １１上で分離し 、１０％ウシ胎仔血清を含むＩ”ｔＰＭＩ−１６４０培地に再懸濁し、分離した 日のうちに検定した。自己の細胞は、ＣＴＬ活性について検査するのと同一の患 者から得たＢリンパ球から調製した。これは、標準細胞と作用細胞の双方のＨＬ Ａ型を一致させるためである。自己のリンパ芽球様細胞株を、これらのＨＩＶ血 清陽性患者から採取して調製するため、Ｅｐｓｔａｎ−Ｂａｒウィルスを用いた 変換を行なった。Separate unfractionated PBMC on 1 (ypaque/Fico 11) , resuspended in I”tPMI-1640 medium containing 10% fetal bovine serum, and isolated. I tested it on the same day. Autologous cells were collected from the same patient tested for CTL activity. It was prepared from B lymphocytes obtained from a person. This is the HL of both standard and working cells. This is to match the A type. Autologous lymphoblastoid cell lines were added to these HIV blood cells. Epstan-Bar virus was used to collect and prepare from seropositive patients. performed the conversion.
これらの細胞株を標的として、自己細胞クロム放出検定を実施した。この検定は Ｋ ｏ ｅ ｎ ｉ ｇらの記載に依存した。本検定では、標識した標的細胞の 融解により、クロムが培地上に遊離される。新たに単離した自己のＰＢＭＣを作 用細胞として使用した。２名の被験者はｎｅｆ特異性の細胞毒性反応を示し、そ の強度はワタシニアウィルスに感染させた対象標的細胞で観察されたものの約５ 倍に達した。Autologous chromium release assay was performed targeting these cell lines. This test is We relied on the description of K.o.e.n.i.g. In this assay, labeled target cells Melting liberates chromium onto the medium. Create freshly isolated autologous PBMC. The cells were used for commercial purposes. Two subjects showed nef-specific cytotoxic responses; The strength of It has doubled.
（ｃ）Ｎｅｆ特異性ＣＴＬエピトープのマツプ作成前記２名の血液提供者のｎ、 ｅ ｆ特異性のＣＴＬ反応については、個々にｎｅｆのタンパク質配列全体を 網羅する一連のペプチド類を使用した検定を実施し、さらに検討した。(c) Creating a map of Nef-specific CTL epitopes n of the two blood donors, For e f-specific CTL reactions, the entire nef protein sequence was individually Assays using a comprehensive series of peptides were performed and further investigated.
直線配列が重複するようにしてｎ、ｅｆ部分を含む１６１１ｉのペプチド類を合 成した。長さは塩基２５個分で、１３個のｘｉ塩基が生じた。このペプチド類は 、下記（ｄ）で記載する方法で作成した。自己細胞にはＣｒ５ ］による１１１ １ｇの前に、１２時間にわたって２５ないし５０％Ｍのペプチド暴露を行なった 。クロム遊離検定を文献通りに実施した。 １個のペプチドがＣＴＬの標的どし て認識され、これをＮｅｆ７と命名したが、これはアミノ酸配列の７３番目から ９７番目に相当することが判明した。このエピトープのＮ末端およびＣ末端の境 界部分については、ペプチド欠損によって詳細なマツプが作成されたゆこれに使 用したペプチドの概要を表１に示す、、１０個の塩基から成るペプチドｎｅｆ７ Ｂは塩基配列の７３番目から８２番目に相当するが、これはＮｅｆ７と同一の反 応性によりＣＴＬエピトープとして機能することが可能である。Combine 1611i peptides containing n and ef parts such that the linear sequences overlap. accomplished. The length was 25 bases, resulting in 13 xi bases. These peptides , was created by the method described in (d) below. 111 by Cr5] for autologous cells 1 g was preceded by 25-50% M peptide exposure for 12 hours. . Chromium release assay was performed as described in the literature. One peptide is a CTL target It was recognized as Nef7 and was named Nef7. It turned out to be number 97. The N-terminal and C-terminal boundaries of this epitope For the boundary part, a detailed map was created by peptide deletion, which was used for this purpose. A summary of the peptides used is shown in Table 1. A peptide nef7 consisting of 10 bases B corresponds to the 73rd to 82nd base sequence, which is the same antipodal as Nef7. Depending on its responsiveness, it can function as a CTL epitope.
ＮｅｆＣＴＬ活性を示した被験者は＃Ｊおよび＃２とした。Subjects who showed NefCTL activity were designated #J and #2.
ペプチドＮｅｆ７Ｂは、Ｎｅｆのタンパク質配列のきわめて良く保持されている 部位に含まれている。現在までに配列の決定された全てのＨＩＶ−１単離株のう ち少なくとも９０％が保持されている。これらの被験者は標準的なスクリーニン グ法で血清陽性に分類されたがＮｅｆに対する抗体反応は放射線免疫検定法では 陰性であった。Peptide Nef7B is a highly conserved protein sequence of Nef. included in the part. All HIV-1 isolates sequenced to date of which at least 90% is retained. These subjects underwent standard screening. Although the antibody reaction to Nef was classified as seropositive by the radioimmunoassay method, It was negative.
（ｄ）ペプチド合成 合成ペプチド類の構築には、Ｍｅ ｒ ｉ ｆ ｉ ｅ ｌ ｄ （Ｊｏｕｒｎ ａｌｏｆ Ａｍｅｒｉｃａｎ Ｃｈｅ＋＊１ｃａｌ ５ｏｃｉｅｔｙ、 １．９ ６３年８５巻、２１４９頁）の段階的同相法を使用し、Ａｐｐｌｉ、ｅｄ Ｂｉ ｏｓｙＳｔｅ−のＭｏｄｅｌｌの４３ＯＡペプチド合成機を使用した。全ての合 成ペプチド類は、メチ１／ンおよびジビニルベンゼンから成る不溶性共重合体の ［ＰＡ、Ｍｊ耐樹脂上集めた。(d) Peptide synthesis For the construction of synthetic peptides, alof American Che+*1cal 5ociety, 1.9 Appli, ed Bi A Model 43OA peptide synthesizer from osySte- was used. All combinations Synthetic peptides are insoluble copolymers of methane and divinylbenzene. [Collected on PA, Mj resistant resin.
アスパラギン、グルタミン、アルギニンおよびヒスチジン以外のすべてのアミノ 酸のアシル化合物として、左右対称の無水派生物を使用した。残りの４種類のア ミノ酸は、１−ヒドロキシベンゾトリアゾールエステル類として共役縮合させた 。合成の間２アミノ酸の反応性を有する測鎖を保護した。保護基としてＡ、 ｓ ｐおよびＧ１ ｕにはＯ−ベンジル基、５ｅｒＪ：５よびＴ ｈ ｒにはベン ジル基、Ｃｙｓにはｐ−メチルベンジル基、Ａｒｇにはトシル基、＋（＋、 ｓ にはジニトロフェニル基、Ｔｙｒには２−ブロモベンジルオキシカルボニル基、 Ｔｙｒには２−ブロモベンジルオキシカルボニル基、かつＴｒｐにはホルミル基 を使用した。All amino acids except asparagine, glutamine, arginine and histidine As the acyl compound of the acid, a symmetrical anhydrous derivative was used. The remaining four types Mino acids were conjugated and condensed as 1-hydroxybenzotriazole esters. . During the synthesis a reactive chain of two amino acids was protected. A, s as a protecting group p and G1u are O-benzyl groups, 5erJ:5 and Thr are benzyl groups. zyl group, p-methylbenzyl group for Cys, tosyl group for Arg, +(+, s is a dinitrophenyl group, Tyr is a 2-bromobenzyloxycarbonyl group, Tyr has a 2-bromobenzyloxycarbonyl group, and Trp has a formyl group. It was used.
合成後、ペプチド類はアユゾール２ジメチルサルフアイドおよびエタンジチオー ルの存在下で無水液体フッ化水素により分割した。一旦分割されるとペプチド類 はエーテル中で沈澱し、樹脂から水に３０％（■／■）の割合で氷酢酸を加えた 溶液を使用して抽出された。After synthesis, the peptides are ayusol 2 dimethyl sulfide and ethanedithio. The solution was resolved with anhydrous liquid hydrogen fluoride in the presence of hydrogen chloride. Once split, the peptides was precipitated in ether and 30% (■/■) glacial acetic acid was added to the water from the resin. extracted using a solution.
樹脂から分別されたペプチド類は分析し、次にＶｙｄａｃＣ−４逆相カラムとＢ ｅ ｃ ｋ ｍ、 ａ ｎの一６ｙｓｔｅｍ Ｇｏｔｄ″ＨＰＬＣを使用して 均一性が９５％を上回るまで精製した。各ペプチド中のアミノ酸含有量の補正値 は、精製した物質を６ＮのＨＣｌ中で２時間、１５０″′Ｃで煮沸し、加水分解 を行なりで礪認した。一旦加水分解した後、アミノ酸組成の分析のためＢｅｃｋ ｍａｎのＳｙｓｔｅｍ Ｇｏｌｄ−アミノ酸分析器に供した。The peptides separated from the resin were analyzed and then loaded onto a Vydac C-4 reverse phase column and B e c k m, a n one 6 system Gotd'' using HPLC Purified to >95% homogeneity. Corrected value for amino acid content in each peptide The purified material was boiled in 6N HCl for 2 hours at 150''C to undergo hydrolysis. I confirmed this in action. Once hydrolyzed, Beck was used for analysis of amino acid composition. MAN's System Gold-Amino Acid Analyzer.
（ｅ）ＣＴＬの検定。(e) CTL test.
ＰＢＭＳの調製、自己類似性リンパ芽球体細胞列の発生、および細胞毒性微細検 定は、認知されたウィルスベクターによって感染されていないで５自己類似性リ ンパ芽球体がＮｅｆ７ペプチドによって被覆されている点を除き、前記す項と同 様である。Preparation of PBMS, generation of self-similar lymphoblastoid cell arrays, and cytotoxicity microanalysis The definition is based on 5 self-similar strains that are not infected by a recognized viral vector. Same as above, except lymphoblasts are coated with Nef7 peptide. It's like that.
（ｆ）実験的なＣＴＬ生成の促進方法。(f) Method for promoting experimental CTL generation.
ＣＴＬ促進促進基準は以下の通りである。血清陽性の個人から新たに得たＰＢＭ Ｓを、Ｈｙｐａｑｕｅ／Ｆｉｃｏｌ １によって分離し、１０％人体血清とＮｅ ｆペプチドを含む溶媒中に再懸濁させた後、３日間培養してから、組換えＩＬ− ２を５単位／ｍｌ添加した。The CTL promotion promotion criteria are as follows. PBM freshly obtained from seropositive individuals S was separated by Hypaque/Ficol 1 and mixed with 10% human serum and Ne. After resuspending in a solvent containing f peptide and culturing for 3 days, recombinant IL- 2 was added at 5 units/ml.
３０００ｒａｄの放射線処理の後、ペプチドを５単位／ ｍ １添加し、５日後 にＮｅｆ７ペプチドでパルスされたＰＢＭＣで再刺激し、３０００ｒａｄの放射 線処理の後、洗浄して過剰のペプチドを除去した。細胞は５日間再刺激された。After 3000 rad radiation treatment, 5 units/m1 of peptide was added and 5 days later were restimulated with PBMC pulsed with Nef7 peptide and exposed to 3000 rad of radiation. After treatment, excess peptide was removed by washing. Cells were restimulated for 5 days.
第１表 重複ペプチド 位置 ＱＥＥＥＥＶＧＦＰＶＴＰＱＶＰ１．、ＲＰＩＩＩＴＹＫＡ、Ａ、Ｖ （６１− ８５）ＱＶＰＬＲＰＭＴＹＫＡ、ＡＶＤＬＳＨＦＬＫＥＫＧＧＬ ｆ７３−９７ ）ＦＰＶＴＰＱＶＰｌ、、ＲＰＩＪＴＹＫＡＡＶＤＬＳ ［６８−８８１Ｑ６８ −８８１ＱＶＰＬＲＰ［ｌＬＳ ［７３−８１１＋ＱＶＰ１．、ＲＰＭＴＹＫ （７３−８２）ＶＰｌ、、ＲＰＭＴＹＫ （７４−８２＋ＰＬＲＰＭＴＹＫ ｆ ７５−８２＋ １、、ＲＰ槌ＴＹＫ （７６−８２１ ＱＶＰ１．、ＲＰＭＴＹ （７３−８１）ＱＶＰＬＲＰｈｌＴ ｆ７３−１３０ ）ＱＶＰＬＲＰＩ、ＩＴＦＫ （７３−８２）ＰＭＴＹＫＡＡＶＤＬＳ）ＩＦｌ 、、ＫＥＫＧＧＬ （７８−９７１ＡＡＶＤＩ、５ＨＦＬＫＥＫＧＧＩ−（８３ −９７）Ｓ ＨＦ Ｌ ＫＥＫＧＧＬ （８８−９７＋この発明で「動物」とは 、必ずしも人体とは限らないが、好ましくは人体を意味する。この発明は、特定 の実施例に限定されるものではなく、それ以外の変形もこの発明の特許請求の範 囲に属すること勿論である。Table 1 Overlapping peptide position QEEEEVGFPVTPQVP1. , RPIIIITYKA, A, V (61- 85) QVPLRPMTYKA, AVDLSHFLKEKGGL f73-97 ) FPVTPQVPl,, RPIJTYKAAVDLS [68-881Q68 -881QVPLRP[lLS [73-811+QVP1. , RPMTYK (73-82)VPl,, RPMTYK (74-82+PLRPMTYK f 75-82+ 1., RP mallet TYK (76-821 QVP1. , RPMTY (73-81)QVPLRPhlT f73-130 )QVPLRPI, ITFK (73-82)PMTYKAAVDLS)IFl ,,KEKGGL (78-971AAVDI, 5HFLKEKGGI-(83 -97) S HF L KEKGGL (88-97+What is "animal" in this invention? , does not necessarily mean a human body, but preferably means a human body. This invention The present invention is not limited to the embodiments described above, and other modifications are also within the scope of the claims of this invention. Of course, it belongs to this group.
国際調査報告international search report
Claims (26)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40959689A | 1989-09-19 | 1989-09-19 | |
| US409,596 | 1989-09-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH05502442A true JPH05502442A (en) | 1993-04-28 |
Family
ID=23621182
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2513793A Pending JPH05502442A (en) | 1989-09-19 | 1990-09-19 | Peptides containing the CTL epitope of HIV protein and their use |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0491844A4 (en) |
| JP (1) | JPH05502442A (en) |
| CA (1) | CA2025634A1 (en) |
| WO (1) | WO1991004051A1 (en) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8429099D0 (en) | 1984-11-16 | 1984-12-27 | Pasteur Institut | Closed dna sequences |
| GB8423659D0 (en) | 1984-09-19 | 1984-10-24 | Pasteur Institut | Cloned dna sequences |
| US7232654B1 (en) | 1983-09-15 | 2007-06-19 | Institut Pasteur | DNA sequence of the LTR region of human immunodeficiency virus type 1 (HIV-1) |
| US7205102B1 (en) | 1983-09-15 | 2007-04-17 | Institut Pasteur | Cloned DNA sequences related to the genomic RNA of lymphadenopathy-associated virus (LAV) and proteins encoded by said LAV genomic RNA |
| US7045130B1 (en) | 1984-10-18 | 2006-05-16 | Institut Pasteur | Antibodies against antigens of human immunodeficiency virus (HIV-1) |
| US5980900A (en) * | 1984-10-18 | 1999-11-09 | Institut Pasteur And Centre National De La Recherche Scientifique | Amino acid DNA sequences related to genomic RNA of human immunodeficiency virus (HIV-1) |
| US5705612A (en) | 1984-10-18 | 1998-01-06 | Institut Pasteur And Centre National De La Recherche Scientifique | NEF peptide encoded by human immunodefiency virus type 1 (HIV-1) |
| US6894152B1 (en) | 1984-11-16 | 2005-05-17 | Institut Pasteur | Cloned DNA sequences related to the genomic RNA of lymphadenopathy-associated-virus (LAV) and proteins encoded by said LAV genomic RNA |
| US5128319A (en) | 1987-08-28 | 1992-07-07 | Board Of Regents, The University Of Texas System | Prophylaxis and therapy of acquired immunodeficiency syndrome |
| US6210873B1 (en) | 1987-08-28 | 2001-04-03 | Board Of Regents, The University Of Texas System | Methods and compositions for the priming of specific cytotoxic T-lymphocyte response |
| US5993819A (en) * | 1987-09-08 | 1999-11-30 | Duke University | Synthetic vaccine for protection against human immunodeficiency virus infection |
| US5221610A (en) * | 1988-05-26 | 1993-06-22 | Institut Pasteur | Diagnostic method and composition for early detection of HIV infection |
| EP0521220A1 (en) * | 1991-06-14 | 1993-01-07 | Institut Pasteur | Recombinant immunogenic actinomycetale |
| JPH07502729A (en) * | 1991-12-02 | 1995-03-23 | ボード・オヴ・リージェンツ，ザ・ユニヴァーシティ・オヴ・テキサス・システム | Methods and compositions for inducing an immune or anti-infective response |
| WO1993019775A1 (en) * | 1992-03-31 | 1993-10-14 | Medimmune, Inc. | Administration of liposomes containing peptides or proteins including ctl eptitopes of hiv proteins |
| US5603933A (en) * | 1993-08-31 | 1997-02-18 | Board Of Regents, The University Of Texas | CD4 peptides for binding to viral envelope proteins |
| DE4405810A1 (en) | 1994-02-23 | 1995-08-24 | Behringwerke Ag | Peptides derived from a retrovirus from the HIV group and their use |
| WO1998015658A1 (en) * | 1996-10-10 | 1998-04-16 | Probe International | Compositions and methods for treating viral infections |
| CN1213068C (en) * | 1999-12-23 | 2005-08-03 | 医疗研究局 | Improvments in or relating to immune responses to HIV |
| IL150961A0 (en) | 2000-02-04 | 2003-02-12 | Univ Duke | Human immunodeficiency virus vaccine |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU592258B2 (en) * | 1986-12-30 | 1990-01-04 | United States of America, as represented by the Secretary, U.S. Department of Commerce, The | Synthetic peptides which induce cellular immunity to the aids virus and aids viral proteins |
| WO1989002277A2 (en) * | 1987-08-28 | 1989-03-23 | Board Of Regents, The University Of Texas System | Prophylaxis and therapy of acquired immunodeficiency syndrome |
-
1990
- 1990-09-18 CA CA002025634A patent/CA2025634A1/en not_active Abandoned
- 1990-09-19 EP EP19900914632 patent/EP0491844A4/en not_active Withdrawn
- 1990-09-19 WO PCT/US1990/005343 patent/WO1991004051A1/en not_active Application Discontinuation
- 1990-09-19 JP JP2513793A patent/JPH05502442A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP0491844A1 (en) | 1992-07-01 |
| EP0491844A4 (en) | 1993-02-17 |
| WO1991004051A1 (en) | 1991-04-04 |
| CA2025634A1 (en) | 1991-03-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH05502442A (en) | Peptides containing the CTL epitope of HIV protein and their use | |
| KR100235849B1 (en) | Peptide capable of inducing immune response against hiv and aids preventive or remedy containing the peptide | |
| US4943628A (en) | HIV peptide-inducted T cell stimulation | |
| JP2569185B2 (en) | Synthetic antigen eliciting anti-HIV response | |
| US5700469A (en) | HIV-1 core protein fragments | |
| Romero et al. | Immunization with synthetic peptides containing a defined malaria epitope induces a highly diverse cytotoxic T lymphocyte response. Evidence that two peptide residues are buried in the MHC molecule. | |
| JPH01501939A (en) | Immunosuppressive peptides and usage | |
| AU675204B2 (en) | Induction of cytolytic T-lymphocytes with cytomegalovirus polypeptides | |
| AU632683B2 (en) | Peptides stimulating cytotoxic t cells immune to hiv rt | |
| US5976541A (en) | Potent peptide for stimulation of cytotoxic T lymphocytes specific for the HIV-1 envelope | |
| PT2044950E (en) | Attenuated vif dna immunization cassettes for genetic vaccines | |
| JPH10503473A (en) | Hepatitis C virus core peptide for cytotoxic T lymphocyte stimulation and HCV exposure diagnosis | |
| WO1992005196A1 (en) | Aids therapy and vaccine | |
| US6210873B1 (en) | Methods and compositions for the priming of specific cytotoxic T-lymphocyte response | |
| RU2337922C9 (en) | ISOLATED POLYPEPTIDES BASED ON NEUTRALISING OF PROTEIN p17 OF HIV VIRUS, USED AS VACCINES, AND NEUTRALISING ANTI-p17-ANTIBODIES, SPECIFICALLY RECOGNISING SAID NEUTRALISING | |
| US5346989A (en) | Peptides for use in induction of T cell activation against HIV-1 | |
| US7521426B2 (en) | HIV-specific CTL inducing peptides and medicaments for preventing or treating AIDS comprising the peptides | |
| US6207161B1 (en) | Induction of cytolytic T-lymphocytes with cytomegalovirus polypeptides | |
| US7319000B1 (en) | Compositions and methods for eliciting immune or anti-infective responses | |
| EP0671947B1 (en) | Compositions for eliciting cytotoxic t-lymphocyte responses against viruses | |
| DE69433057T2 (en) | PEPTIDES FOR USE IN VACCINATING AND INDUCING NEUTRALIZING ANTIBODIES AGAINST THE HUMAN IMMUNITY VIRUS | |
| AU1906592A (en) | Peptides for use in induction of t cell activation against hiv-1 | |
| US20030203841A1 (en) | T20/DP178 and T21/DP107 are activators of human phagocyte formyl peptide receptors | |
| JPH05506039A (en) | Peptides and peptide fragments useful in therapy | |
| Sundaram | Evaluation of T-cell and B-cell epitopes and design of multivalent vaccines against HTLV-1 diseases |