TW201138815A - Peptide vaccine - Google Patents

Abstract

Disclosed is a peptide which has a good immunogenicity and is capable of inducing an enhanced antibody productivity and additional administration of which can enhance the production of the target antibody. Specifically disclosed is a peptide comprising the amino acid sequence of a cell-binding motif of a cell adhesion molecule, an amino acid sequence (T) containing the amino acid sequence of a T cell epitope having an established immunological memory, an amino acid sequence (B) containing the amino acid sequence(s) of one or more specific B cell epitopes of an antigen, and the amino acid sequence of a linker peptide that is positioned between the aforesaid amino acid sequences (T) and (B) in such a manner as to link these amino acid sequences, characterized in that the amino acid sequence of said linker peptide is GKK, VKK or VVKK. Also disclosed are a medicinal composition which comprises the aforesaid peptide as the active ingredient and use of the same.

Description

201138815 VI. Description of the Invention: [Technical Field] The present invention relates to a peptide which is superior in immunogenicity and which is capable of more efficiently inducing the production of antibodies against antigens, one containing A pharmaceutical composition in which a peptide is an active ingredient and its use. More specifically, the present invention relates to a peptide which is capable of more efficiently inducing an antibody against a specific B cell epitope of a human amyloid peptide (hereinafter abbreviated as "A peptide"), and a The composition of the peptide as an active ingredient and a use thereof for preventing and/or treating a neurodegenerative disease caused by Alzheimer's disease caused by Α Lusheng peptide (Neurodegenerative disease) ° [Prior Art] In the case of in vivo induction of specific antibodies against specific antigens, it is generally used to use the purified antigen alone or with an immunological adjuvant capable of enhancing the activity of antibody production ( A method of administering a substance that specifically enhances an immune response against an antigen by non-specifically stimulating an immune mechanism, together with administration to an organism. This method is widely used as the most effective preventive measure for various infectious diseases. In particular, viruses that are not effective against antibiotics or toxins produced by microorganisms. In the absence of other effective preventive or therapeutic methods, in most cases the only policy is to induce antibodies against the virus or toxin in the body to defend. What is currently being used in this way is the use of organic solvents, ultraviolet radiation, etc. to inactivate pathogenic microorganisms, so that the vaccines and pathogens that are not infectious are attenuated to attenuate the pathogenicity of the organisms.

3 S 201138815 In addition to the polio vaccine, etc., it is administered by injection. However, inactivated vaccines or live vaccination ΐΠΐΠ organisms cause anaphylactic shock. Further, since the virion itself or the protein mw is entangled in the material immunogen, and in order to maintain the stability in the case of the medicinal agent I, there is also a case where it is a stabilizer of one dose. The situation can not be ruled out for the use of such stabilizer substances ~ negative for the formation of an unknown infectious microorganism ' or anaphylactic shock to the stabilizer for the organism. & most of the vaccine is formulated as an injection, and Vaccine preparations other than injections are needed. On the other hand, the world is also diligently developing and researching some amino acids that are safer and more effective than inactivated or live vaccines, and that use inactivated vaccines or live vaccines. A novel vaccine of a multi-peptide consisting of a sequence. Representative examples of such novel vaccines are genetic recombinant vaccines or composite vaccines represented by hepatitis A virus vaccines. However, although utilized as a vaccine The shorter the chain length of the peptide is better, but the shorter the bond length, the broader the masking of the major histocompatibility complex of each organism (hereinafter, abbreviated as the Π-type single type) The haplotype is restricted and becomes difficult to design as a person with sufficient immunogenicity. A method for raising the immunogenicity of an antigen when administered via a mucosa is known. Toxin or a heat-labile enterotoxin derived from Escherichia coli, or a method in which these amino acid sequences are partially substituted and attenuated as an immunoadjuvant (Non-patent literature). However, there are In addition to the antigen of interest, the problem is that the cholera toxin used as the immunoadjuvant 201138815 or the antibody derived from the heat-labile enterotoxin of Escherichia coli is not provided for practical use. The present invention provides a peptide having novel structural characteristics by developing a peptide which is capable of sufficiently producing an antibody of interest without using an immunological adjuvant and which can be safely administered (Patent Document 1). Patent Document 1 discloses a peptide having an amino group sequence having an amino acid sequence containing a tau cell epitope, and an insertion link at the amino terminal (hereinafter, abbreviated as N-terminal J) side. An peptide (iinker peptide) having a amino acid sequence containing an amino acid sequence of a B cell epitope, having a cell adhesion molecule at the end of the slow base (hereinafter abbreviated as "C-terminal") The amino acid sequence of the cell-binding motif. The peptide having such a structure is administered via the mucosa through the nose or the like in the absence of an immunological adjuvant. The simple form enhances the production of specific antibodies against the antigen of interest more effectively. Moreover, it is clear that the antibody other than the specific antibody of the target is low in induction ability and does not induce side effects such as allergy. Further, it is known that the above-mentioned peptide has an immunoadjuvant effect. It has been revealed that the present inventors have further produced a structure which is more effective in inducing resistance against human Aj3 antibodies according to the structural characteristics disclosed in Patent Document 1. The resulting peptide is used in the treatment of Alzheimer's disease (Patent Document 2). That is, Patent Document 2 discloses the following peptides: The amino acid sequence (hereinafter sometimes abbreviated as "T") of the amino acid sequence constituting the T cell epitope of the immune memory, and the linker peptide (hereinafter sometimes referred to as "L") is inserted. The c-terminal side has an amino acid sequence (hereinafter, sometimes abbreviated as "B") containing the amino acid sequence of 201138815 or 2 or more b cell epitopes of A]8 peptide, and further selected from the group consisting of At least one position of the N-terminal side of τ, between T and L, between L and B, and at the c-terminal side of B has an amino acid sequence of a cell-binding motif of a cell adhesion molecule. Alzheimer's disease (hereinafter, abbreviated as "AD") accounts for the majority of the main causes of dementia in the elderly, and is a disease in which the quality of life (QOL) is significantly reduced due to memory impairment and movement disorders in patients. Further, it is also a disease that requires a large amount of care in addition to the treatment of the disease, so that the medical cost burden such as loss of work opportunity and mental burden is increased not only during the time of the caretaker of the patient himself or his family, but also The social burden has also increased. In advanced countries that are ageing, dementia is becoming a serious problem as the number of patients increases. AD is a severe neurodegenerative disease without radical therapy, characterized in that it is pathologically composed of 42 amino acid (sequence number in the sequence listing) or 4 amino acid (sequence number 2 in the sequence listing). The A/3 formed is deposited in the central nervous system, that is, the so-called "old spot" deposition, the change in fibrils, and the degeneration and shedding of nerve cells. The treatment of AD is carried out by a clinical trial of a brain neuroprotective agent by treatment with a cholinesterase inhibitor or by a hyperlipidemia agent or eicosapentaenoic acid (EP).

In the development of AD treatment methods, vaccine development has been carried out as a target molecule in the role of AD. (Non-patent literature & also, new types of anti-A /3 monoclonal antibodies, DNA vaccines, CpGDNA, etc. The development of an adjuvant, a peptide vaccine for oral administration, etc. However, since the DNA vaccine is MHC帛I type-restricted, it is easy to induce activation of cytotoxic T 201138815 cells, and thus it is considered to be unsuitable for ad. Treatment. Victory vaccines have low immunogenicity and low ability to induce antibodies against A cold, so most of them require adjuvants to induce antibody production, and may cause excessive immune response caused by the use of adjuvants. The antigen-higher molecule contains multiple tau cell epitopes and sputum cell epitopes, and thus has an excessive immune response against these epitopes. Such excessive immune response may cause unexpected The inflammatory response, but there is a risk of side effects such as encephalitis caused by this inflammatory reaction. Therefore, the fundamental treatment of AD has not yet been established. Also, although A / is known S is related to the onset and deterioration of various diseases other than AD, but a preventive method or a therapeutic method for such diseases has not yet been established. [Patent Document 1] International Publication No. WO2004/087767. [Patent Document 2] International Publication No. WO2007/097251. [Non-Patent Document 1] Lavelle (Lavelle EC), "Mucosal Immunogenicity of Plant Lectins in Mice", Immunology, 2000, Vol. 99, No. 1, p 30-37. [Non-Patent Document 2] Agadjanyan et al. (Agadjanyan MG), "Prototype Alzheimer's disease vaccine using the immunodominant B cell epitope from beta-amyloid and promiscuous T cell epitope pan HLA DR-binding peptide", Journal of Immunology , 2005, Vol. 174, No. 3, p 1580-1586. 201138815 [Summary of the Invention] Previously, the present inventors have developed a peptide having novel structural characteristics, which is superior in immunogenicity and can be used without an immunological adjuvant. That is, a sufficient amount of the antibody of interest can be induced in the living body and can be administered safely. That is, the following peptides are disclosed (patent 1): an amino acid sequence having an amino acid sequence comprising a tau cell epitope, and having a linker peptide inserted on the N-terminal side, and an amino acid comprising a B cell epitope on the C-terminal side Among the peptides of the amino acid sequence of the sequence, the amino acid sequence having the cell-binding motif of the cell adhesion molecule (Patent Document 1), and based on such structural characteristics, the following peptides are produced and disclosed: more effective a peptide which induces the production of an anti-A/5 antibody, that is, an amino acid sequence (T) having an amino acid sequence comprising a T cell epitope determined to constitute an immunological memory in an organism on the N-terminal side and Inserting a linker peptide (L), and having an amino acid sequence (B) comprising an amino acid sequence of one or more b cell epitopes of A) 8 peptides on the c-terminal side, An amino acid sequence having a cell-binding motif of a cell adhesion molecule at least one position selected from the N-terminal side of τ, between T and L, between L and B, and at the C-terminal side of B (Patent Document 2) . It is considered to utilize this peptide to produce higher anti-a/5 antibodies in normal mice. The subject of the present invention is to provide a peptide which is superior in immunogenicity and has a higher ability to induce antibody production. Another object of the present invention is to provide a peptide which is superior in immunogenicity and has a higher ability to induce antibody production, and can be enhanced by additional administration to produce an antibody of interest. Peptide, the peptide system: immunization 201138815 is superior in origin, has higher ability to induce antibody production, and can enhance the production of the antibody of interest by additional administration, and further, the antibody induced by the peptide is finally administered. The peptide is rapidly reduced. Another object of the present invention is to provide a pharmaceutical composition containing the peptide as an active ingredient. In order to solve the above problems, the inventors of the present invention have focused on the respective structural elements contained in the A/3 peptide vaccine disclosed in Patent Document 2, that is, focusing on T cell epitopes and linkers, respectively. The amount of antibody produced in the winning and B cell epitopes. Therefore, the investigation of a less antigenic linker peptide was carried out, and as a result, it was found that a peptide containing the following amino acid sequence can more efficiently induce the production of an antibody of interest: an amine of a cell-binding molecule of a cell adhesion molecule a base acid sequence, an amino acid sequence of a T cell epitope, an amino acid sequence of a B cell epitope, and an amine represented by a GKK, VKK or VVKK (SEQ ID NO: 3 in the Sequence Listing) as a linker peptide Base acid sequence. Further, the present inventors have found that when the peptide is administered in an additive manner, the production of the antibody of interest can be further enhanced as compared with the conventional peptide, and the present invention has been completed. That is, the present invention relates to the following: 1. A peptide or a salt thereof having the amino acid sequence represented by the formula: 尺1_丁一112-1^- R3 — B — R4 The 'τ line indicates an amino acid sequence containing an amino acid sequence constituting the T cell epitope of immunological memory, and the L line indicates the amino acid sequence of the linker peptide. The B line indicates that the antigen contains a specific one or two. The amino acid sequence of the amino acid sequence of the above B cell epitope, at least one of R1, R2, R3 and R4 is the amino acid sequence of the cell binding unit of the cell adhesion 9 201138815; The amino acid sequence of the linker peptide is an amino acid sequence represented by GKK, VKK or VVKK. 2. The peptide of the above 1. or a salt thereof, wherein the 'T cell epitope is derived from one or more peptides selected from the group consisting of antigens selected for use as vaccination against diphtheria 'tuberculosis, tetanus, and whooping cough The amino acid sequence of the peptide. 3. The peptide of the above 1. or 2. or a salt thereof, wherein the 'B cell epitope is an amino acid sequence having an amino acid sequence comprising a B cell epitope of the A/3 peptide. 4. The peptide of the above 3. or the salt thereof, wherein the amino acid sequence of the B cell epitope of the A|8 peptide is the first amino acid from the N terminus of AjS to the 15th The amino acid sequence (SEQ ID NO: 4 in the Sequence Listing), or the first amino acid from the N-terminus of Aj8 to the 13th amino acid sequence (SEQ ID NO: 5 in the Sequence Listing). 5. The peptide of the above 4. or a salt thereof, which is composed of an amino acid sequence selected from any one of Sequence Nos. 6 to 11, 13, 3 and 44 in the Sequence Listing. 6. A peptide or a salt thereof, which is composed of an amino acid sequence selected from any one of Sequence Nos. 6 to 11, 13, 3 and 44 in the Sequence Listing. 7. A peptide or a salt thereof, which consists of the amino acid sequence of SEQ ID NO: 6 in the Sequence Listing. 8. A peptide or a salt thereof is composed of the amino acid sequence of SEQ ID NO: 7 in the Sequence Listing. 9. A peptide or a salt thereof, which is composed of the amino acid sequence 10, 201138815 acid sequence of SEQ ID NO: 8 in the Sequence Listing. The species or its salt is composed of the amino acid sequence of SEQ ID NO: 9 in the Sequence Listing. U• A peptide or a salt thereof, which is composed of the amino acid sequence of SEQ ID NO: 10 in the Sequence Listing. 12. A peptide or a salt thereof, which consists of the amino acid sequence of the sequence number u in the sequence listing. 13. A peptide or a salt thereof, which consists of an acid sequence of the sequence number 丨3 in the sequence listing. 14. A peptide or a salt thereof, which is composed of the acid sequence of SEQ ID NO: 43 in the Sequence Listing. 15. The peptide or a salt thereof is represented by the acid sequence of SEQ ID NO: 44 in the Sequence Listing. Composition. 16. A pharmaceutical composition selected to be selected from the above 1 to

The above-mentioned additives for preparations permitted in the preparation of the preparations. 15_At least 18. A pharmaceutical composition capable of inducing the production of an antibody against & A, containing the peptide of the above-mentioned items 3. to 15. or a salt thereof, and the above-mentioned preparation of the above-mentioned formula Additives for formulation. 19. The pharmaceutical composition according to any one of the above 16 to 18, which is for use in the prevention and/or treatment of a disease caused by A/?.

A drug composition for at least one disease of Alzheimer's type dementia 11 201138815 , mild cognitive impairment, old car, y ^ sedition dementia, Down's syndrome, and amyloidosis. 21. The pharmaceutical composition according to any one of the above 16 to 18, which is for use in the prevention and/or treatment of Alzheimer's disease. , ', 22. The DNA '' encodes a peptide of any of the above 丨 to 15. According to the present invention, it is possible to provide a winning form which is superior in immunogenicity and has a higher ability to induce antibody production, and can be enhanced by additional administration to produce an antibody of interest. According to the present invention, it is possible to further provide a pharmaceutical composition which is superior in immunogenicity, has a high ability to induce antibody production, and can enhance the production of an antibody of interest by additional administration. Active ingredients. Further, by the present invention, the following peptides can be provided, which are superior in immunogenicity, have higher ability to induce antibody production, and can be enhanced by additional administration to produce an antibody of interest' induced by the peptide. The antibody is rapidly decreased after the continuous administration of the peptide, and the possibility of side effects caused by an immune reaction such as an excessive inflammatory reaction caused by an antibody whose antigen is rapidly decreased after the administration of the antibody is low. A major advantage can be obtained as follows: For vaccines against internal antigens such as A cold, the associated side effects are small. [Embodiment] 1. The peptide peptide of the present invention relates to a peptide or a salt thereof, which has a 12 201138815 amino acid sequence represented by the following formula, wherein the τ system indicates that the τ cell antigen constituting the immune memory is determined. The amino acid sequence of the amino acid sequence of the region, the L system represents the amino acid sequence of the linker peptide, and the lanthanide system represents the amino acid sequence of the specific one or more sputum cell epitopes containing the antigen. The amino acid sequence, at least one of R1, R2, R3 and R4 is an amino acid sequence of a cell binding molecule of a cell adhesion molecule, characterized in that the amino acid sequence of the linker peptide is GKK, The amino acid sequence represented by VKK or VVKK. (Formula) R1-T-R2-L-R3-B-R4 The description of the amino acid sequence in the present specification is described in the following three words in the three tables of the sequence table. The peptide of the present invention has an ability to induce production of an antibody against the Β cell epitope region or the amino acid sequence containing the peptide, and the production of the antibody of interest can be enhanced by additionally administering the peptide. The antibody of the present invention is mainly an immunoglobulin G (IgG), an immunoglobulin M (IgM), an immunoglobulin A (IgA) antibody, and includes an antibody secreted in blood or a body fluid, and is also secreted in the nasal cavity. , antibodies to the mouth, eyes, digestive tract, etc. The peptide of the present invention is characterized in that an amino acid sequence comprising an amino acid sequence of a T cell epitope is interposed with an amino acid sequence comprising an amino acid sequence of a B cell epitope, such that The amino acid sequence of the linker peptide of the amino acid sequence represented by GKK, VKK or VVKK is arranged in a linked manner. In the prior disclosure (Patent Documents 1 and 2), as a link 13 201138815 sub-peptide, a recognition sequence of a protease related to antigen processing is exemplified, in particular, a double win, and it is recommended that The recognition sequence of cell autolytic enzyme B is a double peptide composed of aminic acid-isoleic acid (KK). However, the A0 peptide vaccine produced by using a peptide composed of κκ as a linker peptide has a situation in which the amount of anti-A0 antibody production is not increased or increased when repeated immunization is repeated. In addition, as shown in the following examples, the A/3 peptide vaccine produced by the peptide consisting of the amino acid sequence represented by GKK, VKK or VVKK as the linker peptide is used as the double peptide of KK. The AjS peptide vaccine produced by the linker peptide showed higher anti-A/3 antibody-inducing ability, and the amount of antibody production caused by additional administration was increased to a large extent. Since the site of attachment is not directly related to the site in which the antibody of interest is induced, it is considered that the same result can be obtained by substituting the B cell epitope of the other antigen for the B cell epitope of the peptide. Further, a peptide vaccine prepared by using a peptide consisting of an amino acid sequence represented by GKK, VKK or VVKK as a linker peptide is a peptide vaccine produced by a double peptide which is composed of κκ as a linker peptide. The concentration of anti-antibody in the blood decreased rapidly after the end of the administration. It is generally known that 'the shortcoming of vaccines is that once the immune response induced by the vaccine is caused, it is not easy to control the immune response or it is not easy to return to the original state', which may cause side effects such as excessive inflammatory reaction caused by it. After that. However, the peptide vaccine of the present invention is rapidly reduced in the concentration of the antibody of interest in the blood after the administration is completed, so that the possibility of inducing side effects is small. In particular, the greater advantage is that the side effects of the vaccine against the internal antigen are less. Further, the peptide peptide prepared by the peptide of the amine 14 201138815 represented by GKK, VKK or VVKK as a linker peptide has a rapid decrease in the concentration of the anti-A/3 antibody in the blood after the end of the administration. It is considered that the same is true even if the length of the amino acid sequence containing the B cell epitope determined by AjS is changed, and therefore it is not affected by the difference in the B cell epitope, but depends on the link. The difference in the sequence of the sub-peptide. Therefore, in the peptide vaccine of the present invention, even if the B cell epitope of the other antigen is replaced with the B cell epitope of the other antigen, the concentration of the antibody of interest in the blood after the end of administration is rapidly decreased. Therefore, the AjS peptide vaccine produced by the peptide composed of the amino acid sequence represented by GKK, VKK or VVKK as a linker peptide has an extremely high ability to induce an antibody and has a high safety. In view of the higher ability to induce antibody production, an A|S peptide vaccine prepared by using a peptide consisting of an amino acid sequence represented by GKK as a linker peptide is more preferred. The "antigenic region", also referred to as an antigenic determinant, in the present invention means a specific structural unit of an antigen molecule which is recognized by T cells, B cells and antibodies involved in an immune reaction, and has 6 to 10 amino acid sequences. Or 5 to 8 monosaccharide sequences. The term "antigen" refers to a general term for substances that stimulate an organism and cause an immune response such as antibody production or cellular immunity. Generally speaking, it refers to a protein that causes an immune response. Although antibodies are produced to combat various organic substances such as sugars, lipids, and nucleic acids, substances other than proteins generally exhibit antigenic activity in the case of binding to proteins to form a complex. Specific structural units of antigen molecules recognized by T cells and B cells are referred to as "tau cell epitope" and "B cell epitope", respectively. In the peptide of the present invention, the B cell epitope is used as an inducing antibody

15 S 201138815 The part produced. The amino acid sequence of the B cell epitope is derived from antigens such as toxins, allergens, enzymes, cell membrane antigens, tumor-specific antigens, etc. of microorganisms, cells, or tumor cells, which are well-known in the literature. The amino acid sequence of the antigen determining region itself, various antigens which are actually immunogenic to the organism itself, or immunological treatment of a part of the peptide of the antigen by a usual method; The peptide of the amino acid sequence of t can be used as the b cell epitope. The HB cell epitope can be located in the same antigen as the following cell epitope, or can be a shared B cell. The antigenic determining region and a portion or all of the amino acid sequence of the B cell epitope. Therefore, the B cell epitope-determining portion can be prevented or treated according to an inflammatory disease such as infection, cancer, tumor, ulcer, hepatitis or the like, an allergic disease such as acne dermatitis, or the like. A preferred antigenic peptide is selected for the purpose of antibody use such as detection of various antigens used in enzyme neutralization, clinical examination, and the like. The peptides comprising the B cell epitopes can be used directly, or they can be linked in series to be used as dimers, trimers or multimers. Further, two or more B cell epitopes present on the same antigen may be linked in series, or the entire antigen may be used as a B cell antigenic region. Further, when treating a disease associated with a plurality of antigenic proteins, the B cell epitopes can be linked in series to design an antibody against a plurality of antigenic proteins by using one victory. In this case, the recognition sequence of the protease associated with the above antigen treatment is inserted between the respective B cell epitopes as a linker peptide, whereby the treatment of each antigen-determination region can be performed more surely. 201138815 In the triumph of the present invention, the B cell epitope determined by the A/3 peptide is used as the part & of the induced antibody production, whereby the antibody which induces the anti-A antibody can be produced. The "B cell epitope" of A/3 peptide refers to the amino acid sequence containing the B cell epitope of Aj3 which is the cause of Alzheimer's disease. Among them, it is preferred to have an amino acid sequence capable of inducing the production of the following antibodies: dissolved A/3 agglutination fibers' inhibiting the deposition of AiS on nerve fibers or other organs, inhibiting binding to acetylcholine, and In particular, a peptide containing an amino acid sequence near the N-terminus of A/3 is preferably composed of about 5 to 20 amino acids. If the amount of the amino acid is too large, the ability to induce antibody production will disappear, and if it is too large, the antigenicity will become high, and on the other hand, there may be an antigen-determining region which produces an antibody which induces side effects. The peptide comprising the B cell epitope can be used as it is, or it can be used in series to be used as a dimer, a trimer or a multimer. Further, if necessary, two or more B cell epitopes present on A/3 may be linked in series, or the total number of AjS, for example, the number of amino acids may be 42 (sequence number in the sequence listing). Hereinafter, A/3 which is abbreviated as "a (j-42)") or 40 (sequence number 2 in the sequence listing, hereinafter abbreviated as "A" (1_40)") is referred to as a B cell epitope. Further, a plurality of epitopes can be linked to design a peptide which can simultaneously induce the production of a plurality of antibodies. In such a case, the recognition sequence of the protease associated with the above antigen treatment can be inserted between the B cell epitopes as a linker peptide, whereby the treatment of each antigen determining region can be performed more surely.

When the peptide of the present invention is used as the B cell epitope in the vicinity of the N-terminal end of A, it is preferred to have at least the fourth one from the end of N 17 201138815 of A cold. The amino acid sequence 'for example, may be exemplified by the amino acid sequence of the DAEFRHDSGYEVHHQ having the -15th in the amino acid sequence shown in SEQ ID NO: 1 or 2 in the Sequence Listing (sequence in the sequence listing) The number 4, hereinafter abbreviated as "Person (1~15)", has the peptide of the amino acid sequence of the 13th DAEFRHDSGYEVH (the sequence number 5' in the sequence listing is abbreviated as "cold (1) — 13)”), a peptide having the amino acid sequence of DAEFRHDSGYE No. 1-11 (the sequence number 14' in the sequence listing is abbreviated as “eight cold”), and the amine of EFRHDSGYE No. 3-11 The peptide of the acid sequence (the sequence number 15' in the sequence listing is abbreviated as "a no (3-11)"), and the peptide of the amino acid sequence of EFRHDSGYEVHHQ of 3-15 (sequence in the sequence listing) The number 16 ' is abbreviated as "a /5 ( 3 - 15 )"). In addition, the B cell epitope of A stone peptide may be exemplified by the amino acid sequence of DAEFRHDSGY having the 丨-丨〇 of the amino acid sequence shown in SEQ ID NO: 1 or 2 in the Sequence Listing. Peptide (sequence number 17 in the sequence listing, abbreviated W (Bu 1)"), with 丨-8

The peptide of the DAEFRHDS (tetra) acid sequence (the sequence number in the sequence listing is 18 or less is "eight/5 (1-8)"), and the peptide of the amino acid sequence of D AEFRH of No. 6 (preface) The serial number of the list is Shima 19, which is abbreviated as "A/5 (1 - 6)"). From the standpoint of inducing the ability or side effects of antibodies against a gamma peptide, it is preferred to use A/5 (1-15) or into the stone (1-13) to use A^(1_15) . The "T cell antigen-determining region constituting the immunological memory" used in the peptide of the present invention refers to a peptide that has been administered to the peptide of the present invention, and has been constructed into an immunological memory in the organism to which the 18 201138815 is administered. For example, in the organism to which the peptide of the present invention is administered, the peptide containing the same τ cell antigen-determining region as the peptide of the present invention is administered in advance to constitute an immunological memory. The tau cell epitope determined by the organism card to form an immune memory is preferably a cell epitope determined to constitute an immune memory in a human body. In other words, most of the vaccinated cells have antigen-determining regions which are obtained by immunizing antigen peptides after vaccination, and can be used even if the above-described operations constituting immunological memory are not performed. Further, for a patient who has already constituted an immune memory, it is expected that the effect can be further improved if the above operation is performed again. The T cell determinant MHC π-type molecule, the HLA-DR molecule, binds to its antigen recognition site (agretope) and is suggested to be a helper T cell antigen. The "antigen-recognition site" refers to an amino acid residue at a site of a tau cell antigen-determining region that binds to an HLA-DR molecule. The T cell epitope is restricted by the hla-DR monotype, so it is preferable to use a multiple-antigen-recognition pattern that is restricted by multiple HLA-DR monotypes (dual genes) as much as possible. A peptide or an amino acid sequence containing the same. The T cell epitope determined for use in the present invention is used as a peptide for antigens in pre-vaccination such as diphtheria, tetanus, sublingual gland, rubella, measles, tuberculosis, etc. In the class, since the early childhood, it constitutes immune memory, so it is better. From the broad point of view, a diphtheria toxoid, tetanus toxoid, phlegm cough, and two kinds of mixed seedlings or BCG (tuberculosis) are inoculated in Sakamoto, and are widely vaccinated in the world. Very good. 19 201138815 Since the amino acid sequence which is used as an antigen peptide in vaccination is well known, the amino acid sequence of the well-known tau cell epitope of the peptide can also be used. In addition, in fact, the blastogenesis reaction of human peripheral blood can also be used to identify the epitope of the antigenic partial peptide of the antigen, and the peptide having the identified amino acid sequence can be used as the tau cell antigen. Decision area. Further, the amino acid sequence of the peptide can be arbitrarily determined by using the available HL A-DR tau cell antigen ruling region prediction program to select a multi-antigen recognition region conjugated to a large number of HLA-DRs. Further, from the viewpoint of side effects, it is preferred that the tau cell epitope is itself less resistant to the antibody-inducing ability of the sigma antigenic region. In addition, 'if the peptide derived from the amino acid sequence of the sensitizing antigen used for vaccination is used as the epitope,' because the epitope is originally used in humans to induce antibodies against this epitope. Therefore, even if the antibody against the antigen-determining region is produced, it has the advantage of being safe and having side effects. These T cell epitopes can be used directly or by randomly linking the same or a plurality of tau cell epitopes. Further, in the T cell epitope, the amino acid residue other than the amino acid residue of the antigen recognition site may be substituted with another amino acid residue, and the T cell epitope may specifically be as follows. The epitope of the amino acid sequence: the epitope determined by the diphtheria toxoid, that is, the peptide having the amino acid sequence AYNFVESIINLFQVVHNSYN (SEQ ID NO: 20 in the sequence listing) (hereinafter, abbreviated as "DiTox ( 20)"), a peptide having the amino acid sequence AYNFVESIINLFQVVHNSY (sequence number 21 in the sequence 20 201138815 table) (hereinafter, abbreviated as "DiTox (19)"), and a peptide having the amino acid sequence YNFVESIINLFQVVHNSYN (preface) The sequence number in the list 22), and the epitope determined from the tetanus toxoid, namely the peptide with the amino acid sequence LQTMVKLFNRIKNNVA (SEQ ID NO: 23 in the sequence listing), the peptide with the amino acid sequence FLQTMVKLFNRIKNNVAG (Order 歹 ij number 24 in the 歹 ij table) (hereinafter, abbreviated as "TetTIL")), a peptide having the amino acid sequence IHVLHGLYGMQVSSHE (in the order of the 歹 ij table) No. 25), a peptide having the amino acid sequence LIHVLHGLYGMQVSSHEI (SEQ ID NO: 26 in the sequence listing), a peptide having the amino acid sequence YIVNEDKFQILYNSIMYG (SEQ ID NO: 27 in the sequence listing), and having the amino acid sequence QYIVNEDKFQILYNSIMYGF Peptide (sequence number 28 in the sequence listing) (hereinafter, abbreviated as "TetT3L"), peptide with amino acid sequence SYQMYRSLEYQVDAI (sequence number 29 in the sequence listing), peptide with amino acid sequence RSYQMYRSLEYQVDAI (preface) The sequence number in the list is 30), the peptide having the amino acid sequence NINIFMRESSRSFLV (the sequence 歹ij number 31 in the sequence 歹 ij), the peptide having the amino acid sequence ININIFMRESSRSFLVN (the sequence number 32 in the sequence listing), The peptide derived from MPT64, which is known to be a common secretory protein of human type and Mycobacterium tuberculosis/bovis, is the peptide having the amino acid sequence IQMSDPAYNINISLPSYYPD (SEQ ID NO: 33 in the sequence listing) (below) , abbreviated as "MptL (43-62)"), with the amino acid sequence IQMSDPAYNINISLPS peptide (sequence number 21 20 in the sequence listing) 1138815 34 ), a peptide having the amino acid sequence DPAYNINISLPSYYPD (SEQ ID NO: 35 in the sequence listing), and a peptide having the amino acid sequence YNINISLPSYYPDQKS (SEQ ID NO: 36 in the Sequence Listing), etc. having an amino acid sequence Antigenic region. Among them, it is preferred that the ability to induce antibody production is high' and that it can be combined with the 47-pair gene and the 39-pair gene in the 51-pair gene which can be combined with HLA-DR predicted by the following HLA-DR restriction prediction program "ProPrep". 41 pairs of even genes, or 5 〇 dual genes are combined and predicted] \^1( 43- 62 ), 〇汀〇\(20), 1^丁11^ and TetT3L, especially DiTox (20). DiT〇x (19)' in the absence of 1 amino acid residue at the C-terminal of DiTox (20). As a result of in silico analysis, it is known that the amino acid at the c-terminus does not affect the antigenicity or multi-antigen recognition function of the peptide. Therefore, it is predicted that it can bind to the same dual gene as DiTox (20), so it can be used in the same way as DiT〇x (2〇). Further, if necessary, the cultured human peripheral blood of the peptide vaccine of the present invention is mixed and cultured. Wait for the T cell epitope, confirm the biochemical reaction of the bud, or apply a small amount to the skin to confirm whether it causes delayed-typed hypersensitivity, confirm the presence or absence of memory tau cells, or choose to vote A preferred cell epitope is preferred. As a result, Tian Yue adheres to the cell binding element of the knife, and the victory of the present invention can be maintained during the long period of the mucosal surface, and only | B g 士At finding ^ ^ 罟疋 has the ability to be administered by oral or nasal transmucosal mucosa. The antibody can be used if it is used to enhance the effect of 谈^4. For example, a binding unit including a chimeric family (ink-fa-), and other cell-binding groups can be used. Amino acid sequence of thiol. For example, the amino acid sequence belonging to the 22 201138815 chimeric element-binding motif can be exemplified as being present in fibronectin, collagen, villectil,

Rgd, RED, LDV, PHSRN (SEQ ID NO: 37 in the sequence listing), RKK, DGEA (recombinant numbers of cell adhesion molecules such as fibrinogen, laminin, Tat protein of human immunodeficiency virus) The amino acid sequence of the sequence number 3 8 ) in the sequence listing. Further, the amino acid sequence of the cell-binding motif other than the chimeric hormone-binding motif can be exemplified by YIGSR (SEQ ID NO: 39 in the Sequence Listing) 'IKVAV (SEQ ID NO: 40 in the Sequence Listing), RFYVVMWK (in the Sequence Listing) Sequence number 41), IRVVM (sequence number 42 in the sequence listing), and the like. Among them, the peptide composed of the amino acid sequences represented by rgD, RED, and YIGSR is preferred because it has a strong ability to induce specific antibodies, and is particularly preferably RGD. Further, in the peptide of the present invention, the linking site of the amino acid sequence of the cell-binding motif of the present invention may be selected from the following four total sites and may be linked to at least one of the sites: T cells are contained. The N-terminal side or the C-terminal side of the amino acid sequence of the amino acid sequence of the epitope, or the N-terminal side or the C-terminal side of the amino acid sequence of the amino acid sequence containing the B cell epitope, particularly a peptide of the present invention which binds to a cell-binding motif of a cell adhesion molecule, because the unilateral side or both sides of the N-terminal side or the C-terminal side of the amino acid sequence of the amino acid sequence containing the T cell epitope is contained In particular, the production of antibodies specific for the amino acid sequence of the amino acid sequence containing the B cell epitope is enhanced, and it is preferred that it is preferably linked to the N-terminal side. Specific examples of the peptide of the present invention include a B cell epitope which contains an A/3 peptide as a site for inducing an antibody, and a peptide which induces the production of an antibody against the A. More specifically, RGD-DiTox (1 9 ) — VVKK — A/3 (1) represented by the amino acid sequence contained in SEQ ID NO: 6-11, 13, 43 and 44 in the Sequence Listing, respectively, can be exemplified. — 1 5 ) (sequence number 6 ), RGD — DiTox ( 1 9 ) — GKK — A (1 – 15) (sequence number 7), RGD—DiTox ( 19 ) — GKK—A卩 (1 – 13) (sequence number g), RGD — DiTox (1 9 ) — GKK — A/3 ( 1 — 10 ) (sequence number 9 ), RGD — DiTox ( 19) — GKK — A/3 ( 1 — 8) (sequence number 1〇), and RGD - DiTox (19) - GKK - A no (1 - 6) (sequence number 11), RGD-DiTox (19) - VKK-A (S (1-15) (sequence number 13), RGD - DiTox ( 19) - VKK- A/3 ( 1 - 13 ) (sequence number 43 ), RGD — DiTox ( 19) - VVKK- A]S ( 1 - 13 ) (sequence number 44). It is recorded that RGD_ DiTox ( 20 ) - KK — A call (1 — 13 ) ' RGD - DiTox (19)- VKK- Αβ ( 1 - 15 ), RGD — DiTox ( 19) -VVKK-A^ (1-15) ' RGD- DiTox ( 19 ) -GKK- Αβ ( 1 - 15 ) , RGD-DiTox ( 19) — GKK-A/S (1-13) > RGD-DiTox ( 19) -GKK-AyS (1-10 ) ' RGD- DiTox ( 19) - GKK - A β (1-8) ' RGD - DiTox (19) - GKK-(1-6) ' Αβ (1-42) > RGD-DiTox (19) - VKK-(1-13 ) ' RGD-DiTox ( 19) - VVKK — A β (1-13) 'RGD—DiTox(Rev) — KK—(1—13) The amino acid sequence and the sequence number in the sequence listing. The method for inventing the peptide is not limited, and may be prepared by a conventional peptide synthesis method or by a conventional peptide synthesis method in combination with a peptide synthesized in advance, which is partially synthesized. Further, the peptide may be prepared. It was synthesized according to the operating procedure of the apparatus (pr〇t〇c〇i) using a commercially available peptide synthesizer from each manufacturer 24 201138815. Further, the peptide of the present invention can be produced by recombinant DNA technology. For example, a DNA encoding an amino acid sequence of a designed peptide can be prepared, inserted into a self-proliferating carrier, and introduced into a microorganism, animal or plant such as coliform, subtilis, radiation, yeast, or the like. In a host such as a cell or a tissue, a transformant is produced to produce a gene-transgenic plant, and after culturing and raising the gene-transfected plant, the peptide of the present invention is extracted and purified by an appropriate method. Further, the cells, animals or plants in which the peptide of the present invention is found can be directly processed, and can be used as an orally ingestible composition containing the peptide of the present invention. The plant may, for example, be a layer of Asteraceae, Brassicaceae, Cucurbitaceae, Apiaceae, Rosaceae, Vitaceae, and vaccinium. ), Caricaceae, Fabaceae, jugiandaceae, Chenopodiaceae, Solanaceae, Convolvulaceae, Poaceae, or Dioscorea (Dioscoreaceae) and other plants, more detailed can be cited lettuce 'chicory, wormwood, broccoli, cabbage, radish, wasabi, mustard, cucumber, cantaloupe, pumpkin, chayote, carrot, C. chinensis (Cryptotaenia japonica Hassk.), preface Dish, apple, plum, plum, peach, strawberry, raspberry, almond, pear, alfalfa, grape, moss, mulberry, blueberry, papaya, alfalfa, soybean, walnut, spinach, tomato, pepper, sweet potato , rice, corn, wheat, barley, tired wheat, yam, horse yam and so on. Further, the peptide of the present invention can be directly prepared by any of the above methods 25 201138815, or can be prepared by chemically combining a peptide having a partial amino acid sequence thereof in advance. . 2. Evaluation of Animals The antibody production ability of the peptide vaccine of the present invention can be evaluated using the following animals: an immunological memory constituting a peptide of a T cell epitope containing the peptide vaccine, and by B cell antigen An animal that determines the region to produce antibodies. Animals include: mice, dogs, cats, goats, sheep, pigs, and non-human primates (eg, rhesus monkeys, stone crab macaques, chimpanzees). In order to investigate the ability of an antibody against A0 peptide vaccine to be produced, for example, it can be confirmed by the following method: a T cell antigen-determining region of RGD peptide toxin and/or tetanus toxoid, and against A/3 A B-cell epitope determined to bind to a T cell epitope and a b cell epitope, a linker of any of GKK, VKK or VVKK, administered to a diphtheria toxoid and/or Tetanus toxoid is used to pre-immunize mice, and the number of antibodies in the blood is checked or the accumulation of Ap in the brain is confirmed. The rats used in the experiment are not limited as long as the effect of the peptide vaccine of the present invention can be confirmed. 'For example, ju mice, b16 mice, Balb/c mice (Sakamoto Charles River Co., Ltd.) A/3 can be found to have a heterogeneous recombination of APP695 called K670N, M671L mutation called swedish mutation. Is0f0rm), A/3 Tg2576 mice with increased capacity (Science, 1996, Vol. 274, p. 99-102). 3. Pharmaceutical composition 26 201138815 A pharmaceutical composition obtained by combining one or two or more kinds of preparation additives which are pharmaceutically acceptable in the peptide of the present invention can be prepared to the extent that the effects of the present invention are not impaired. . Examples of the additives for preparation include a solvent such as water or alcohol, a reducing sugar such as glucose or maltose, a non-reducing sugar such as α,α-trehalose, sucrose or cyclodextrin, or a trehalose of trehalose or maltose. Sugar derivative of trehalose such as 海海藻糖 (Mah〇syl trehai〇se), sugar alcohol such as sorbitol, mannitol, maltitol, maltotriol (maUoiriit〇l), and amaranth 'poly three A water-soluble polymer such as glucose, guar gum or gum arabic, a protein such as alum or silk, or a hydrolyzate thereof, a hydroxyl group, an amino acid, a buffer, a stabilizer, an antibacterial agent, a fragrance, and a nutrient function. Foods, quasi-drugs (quasi or pharmaceutical active ingredients, immunization adjuvants such as alum, hydrazine, or other food additives, pharmaceutical additives, etc., may also be used in combination or combination It is preferably used to stabilize the peptide. The effect of the peptide is higher than that of the sugar and 〇!, 〇; - the sugar derivative of trehalose. Two or more suitable cockroaches: - "The winner of the invention, including the winner All pharmacologically acceptable salts of peptides, S Or a salt of such a vinegar. The pharmacologically acceptable salt may preferably be an alkali metal salt such as a sodium salt, a potassium salt or a lithium salt, such as calcium: an alkaline earth metal such as a magnesium salt. a metal such as an amine salt, an iron salt, a zinc salt, a copper salt, a zinc salt, a cobalt salt, or the like, such as an inorganic salt of an ammonium salt, such as a third octylamine salt: a sulfhydryl salt, a whallin salt (m) 〇rph〇line, 帛 胺 糖 、 、 、 、 、 、 、 、 、 N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N , - cyclohexylamine salt, N, N, - diτ & ethylenediamine salt 27 201138815 (N, N5-dibenzylethylenediamine salt), chloroprocaine salt, procaine salt , an amine salt such as diethanolamine salt, N-benzyl-phenethylamine salt, piperazine salt, tetramethylammonium salt, tris(hydroxymethyl)aminomethane salt or the like Inorganic acids such as hydrofluoride, hydrochloride, hydrobromide, hydroiodide hydrogen halide acid salts, nitrates, peroxyacid salts, sulfates, acidates, etc. , such as sulfonate, trifluoromethanesulfonate, ethane sulfonate, such as Alkane sulfonate, such as phenyl acid salt, p-toluene sulfonate-like aromatic hydroxy Organic salt of arylsulf〇nic acid salt, acetate, malate, fumarate, teponate, broth, tartrate, oxalate, succinic acid salt, etc. An acid salt, and an amine acid salt such as a glycinate, an amidate, a arginine, an alanate, a glutamate or an aspartate.

Further, the form of the preparation containing the peptide of the present invention is not particularly limited as long as the peptide in the preparation can be kept stable for a long period of time, as long as the administration target, the administration method, the preparation method of the preparation, or the transportation method are considered. The preparation form of the solution, the lyophilized product, the lozenge, the sublingual tablet, the throat ingot 'powder, granules, paste, ointment, syrup, etc. may be appropriately selected. Further, the peptide of the present invention or a composition containing the same may be encapsulated in a liposome as needed, and a penetration enhancer or an iontophoresis method in the skin or tissue may be used in combination to promote penetration of the antigen-presenting cell. . ’ ' The winning form of the present invention can be contained in various foods and drinks such as a 5 L dessert, a candy, a refreshing drink, etc., and it is orally taken, whereby the peptide is administered mucosally. Further, the RNA encoding the peptide of the present invention can also be directly administered into a living body and introduced into DNA 28 201138815

The peptide of the present invention is found in vivo in the cells, i.e., gene therapy, & (3) The method of administering the pharmaceutical composition of the present invention as an active ingredient to a human, and there is no particular limitation as long as the peptide of the present invention can surely reach the site of administration, Soldier gp I to do ^i ^ I see and you can. For example, a dropper or a syringe can be appropriately added to the spot film, and the t-T π.a Hao film can also be ingested or applied as a paste or gel to the mucous membrane or induced by a catheter or the like. The predetermined portion may be sprayed by a spray H or a medical spray to be sucked to the nose, the trachea or the lungs. For administration into a body cavity such as subcutaneous, intraorbital, intramuscular, intravascular, intraperitoneal, or intrathoracic cavity, a syringe, a catheter, a drip, or the like can be used. The administration amount of the peptide of the present invention may be appropriately determined in consideration of the ability to induce antibody production, the type of disease, the route of administration, the method of administration, the animal to be administered, and the like, and is usually 〇〇〇〇〇1 to 1〇. The 〇mg/kg body weight is preferably 0.0001 to 25 mg/kg body weight, and more preferably 0 001 to 1 mg/kg body weight. Further, since the peptide of the present invention can effectively induce antibody production in the initial administration, it is additionally administered by using only the peptide having the amino acid sequence of the B cell epitope of the peptide. The situation 'can also enhance the production of antibodies of interest. 3 A pharmaceutical composition having the peptide of the present invention as an active ingredient can be used simultaneously or sequentially with one or two or more other pharmaceutical compositions. After the administration of the other pharmaceutical composition, the pharmaceutical composition containing the peptide of the present invention as an active ingredient may be administered, or the pharmaceutical composition may be administered, and the other pharmaceutical composition may be administered. The pharmaceutical composition is administered simultaneously with the chemotherapeutic agent. Although other pharmaceutical compositions vary depending on the disease of the subject, 29 201138815 may include other vaccines, chemotherapeutic agents, antibody medicines, antisense Nucleic Acid Drugs, and siRNA medicines. The peptide of the present invention or a pharmaceutical composition containing the peptide as an active ingredient can be used as a peptide vaccine. The vaccine is a preparation which is administered for the purpose of giving active immunity against pathogens. Active immunity refers to the induction of an immune response by administration of an antigen. The peptide vaccine refers to a preparation containing a peptide which is composed of an amino acid sequence which actually induces an immune reaction in the amino acid sequence of the protein to exert a part of the defense of the organism. The peptide vaccine of the present invention can select a preferred antigen peptide for use in preventing infection, preventing or treating inflammatory diseases, allergies and diseases such as cancer, tumor, ulcer, hepatitis, etc. according to the purpose of use of the antibody induced by the antibody. An immunological disease such as dermatitis. Alternatively, an antibody for producing various antigens used for neutralizing enzymes, clinical examinations, and the like can be used. In the peptide vaccine of the present invention, the amino acid sequence comprising the amino acid sequence of the B cell epitope can be selected by selecting an amino acid sequence containing the amino acid sequence derived from the B cell epitope of A/3. The base acid sequence is used to obtain a peptide vaccine that induces anti-A antibody production. Such a peptide vaccine may, for example, be RGD-DiTox (19) - VVKK — A/3 (1) represented by the amino acid sequence described in SEQ ID NOs: 6-11, 13, 3, and 44 in the Sequence Listing, respectively. — 15 ) (Serial number 6), RGD — DiTox ( 19) — GKK - A/3 ( 1 - 15 ) (sequence number 7), RGD- DiTox ( 19) — GKK- A/3 ( 1 - 13 ) ( Sequence number 8), RGD - DiTox (19) - GKK - AjS (1 - i〇) (sequence number 9), RGD - DiTox (19) - GKK - AjS (1 - 8) (order 30 201138815 column number 10) And RGD — DiTox ( 19) — GKK — A0 ( 1 ~ (sequence number 11), RGD-DiTox ( 19) - VKK-A|3 ( 1-15) (sequence number 13), RGD-DiTox ( 19) — VKK-Αβ ( 1- 13) (SEQ ID NO: 43) and RGD — DiTox ( 19) — VVKK — A/3 ( 1 — l3 ) (SEQ ID NO: 44), and the pharmacologically acceptable salt of the peptide The peptide of the present invention may be used singly or in combination with one or more other medical products. For example, a choline enzyme inhibitor, NMDA (N-methyl-D) may be mentioned. -aspartate ) Chucosic acid A antagonist Anti-A cold vaccine, anti-A cold antibody, 7-secretase (Secretase) inhibitor, /3 - secretagogue inhibitor, a condensation set inhibitor. Examples of acetylcholine inhibitors include: Donepezil hydrochloride, rivastigmine tartrate, and hydrobromide. Specific examples of the NMDA (N-methyl-D-aspartate) type glutamate receptor antagonist may be referred to as Memantine hydrochloride. Specific examples of the anti-a cold antibody include BaPineuzumab, s〇lanezumab, P〇nezumab, and Gantenrumab. A peptide vaccine which induces the production of the anti-Ay3 antibody of the present invention can be used to prevent or treat a disease caused by A cold. The disease caused by a Θ in the present invention refers to a disease caused by deposition of A 10,000 in a specific tissue, etc. The deposition includes not only the main cause of the cause, but also the deposition of the A stone accompanying other diseases. Diseases that cause or even worsen also include clinical signs associated with such diseases. Specific examples include: package 31 201138815 Motor neurological diseases including the following diseases: Alzheimer's disease (ad), Alzheimer's type dementia (SDAT) 'Alzheimer's disease, frontotemporal dementia ( Frontotemporal dementia), Pick's disease, Down's disease, hereditary amyloid cerebral hemorrhage (Dutch type), mild cognitive impairment' memory impairment, learning disabilities, amyloidosis, cerebral ischemia, Cerebrovascular dementia, diffuse Lewy body disease, progressive supranuclear palsy (Steel-Richardson syndrome), Multi-system degeneration (Shy-Drager syndrome), Amyotrophic Lateral Sclerosis, Degenerative ataxia, Cortical basal degeneration, ALS — Parkinson's - Dementia complex of Guam, Subacute scler〇sing pane Ncephalitis), Huntington's disease, Parkinson's disease, synucleinopathies, primary progressive aphasia, striatonigral degeneration, horse Machado-Joseph disease / Spinocere bellar ataxia type 3 and cerebral cerebellar degeneration (〇iivopont〇cerebellar degeneration), Du Laide Gilles De La Tourette's disease, Bulbar palsy and Pseudobulbar palsy, spinai and bulbar muscular atrophy (Kennedy's 32 201138815 disease), original Primary lateral sclerosis, Familial spastic paraplegia, Werdnig — Hoffmann disease, Kugelberg-Welander Disease), Tay-Sach, s disease, mountain squid (Sandhoff d) Isease), Familial spastic disease, Wohifart — Kugelberg — Welander disease, Spastic paraplegia, progressive multifocal white matter Progressive multifocal leukoencephalopathy, prion disease (Creutzfeldt — Jakob), Gözmann-Strauss-Schnein (Gerstmann – Straussler – Scheinker Disease), age-related dementia, Vascular dementia, Diffuse white matter disease, including Guru and Fatal familial insomnia Binswanger's disease, endocrine or metabolic dementia, head trauma and diffuse brain damage, dementia pugilistica and frontal lobe dementia , including cerebral ischemia or embolic occlusion and thrombotic occlusion Dyeing and neurodegenerative diseases caused by any kind of intracranial hemorrhage (intracranial ΙιεηιαιτΙΐΜ^, intracranial and spinal injury, hereditary cerebral vascular disorders, non-neuropathic hereditary amyloid, Down syndrome, macroglobulinemia (macroglobulinemia), secondary familial Mediterranean fever (Familiar Mediterranean fever), Mackle- Wells syndrome, more 33 201138815 a myeloid, adenalosis associated with pancreatic disease or heart disease, chronic hemodialysis joint disease (Chr 〇nic hem〇dialysis arthr〇M讣^ or a neurodegenerative disease such as Finnish and Iowa type powder degeneration, diabetic degenerative neuropathy, or diabetes caused by A stone deposition in the pancreas, etc. The clinical symptoms associated with the disease. The towel of the above disease is preferably Alzheimer's disease, Alzheimer's type dementia, mild cognitive impairment, senile dementia, Down's syndrome or amyloidosis. The present invention will be more specifically described by the following examples, but the present invention is not limited by the examples shown below. [Example 1] Various A-mouth peptide vaccines were prepared, and Balb//c mice were used to evaluate the ability of each anti-A/J antibody to induce production. The peptide is based on the peptide peptide vaccine of the peptide prototype developed in Patent Document 2, namely RGD-DiTox(20)-KK-Aj8(l-13) (in the sequence table).

The link portion of the sequence number 12) and the B cell epitope region are designed to be converted and synthesized by external entrustment (〇per〇n Bi〇techn〇1〇gies Co., Ltd.). The peptides were all dissolved in PBS in a manner of 1 mg/mL.

The following three species are the only ones: RGD - DiTox ( 20) - KK - A / 3 ( 1 - 13) (sequence number 12 in the sequence listing), rgD- DiTox ( 19) - VKK - A/3 (1 - 15) (sequence number i 3 in the sequence listing), RGD _ DiTox (1 9 ) - VVKK - A/3 (1 - 1 5 ) (sequence number 6 in the sequence listing), RGD - DiTox ( 19) - GKK- AjS ( 1 - 15 ) (sequence number 7 in the sequence listing), RGD - DiTox ( 19 ) - GKK - A/3 ( 1 - 13 ) (Sequence 34 201138815 List number in the list 8), RGD — DiTox ( 19) — GKK- A/3 ( 1 — 1 0 ) (serial number in the sequence listing is 焉 9 ), RGD — DiTox ( 1 9 ) _ GKK -A/5 ( 1 — 8 (Sequence number in the sequence listing, and rgD-DiTox (19) - GKK-A0 (1 - 6) (sequence number ii in the sequence listing). The administration of the peptide to the mouse is carried out as follows. First, 5〇ml/rat precipitated diphtheria tetanus mixed toxoid (manufactured by Kitakami Institute) was administered to the back of the 5-week Balb/c mouse (Japan Charles River Co., Ltd.) for pre-immunization. 2 weeks after autoimmunization The peptide is administered. The administration will be prepared to 1 mg/mL. The peptide solution 50/iL/mouse (50 pG/mouse) was administered to the back of the skin. Four groups of one group were administered with an additional dose of 6 times at intervals of 2 weeks after the initial administration. One week later, the blood was collected from the tail of the mouse, and the plasma component was added. Protease inhibitor cocktail (manufactured by Roche Diagnostics Co., Ltd.) was added to the plasma as an anti-antibody test sample, and '50 μί / mouse PBS was administered to the back of the skin as a negative control group. The test for the amount of anti-spasm/3 antibody in the blood was carried out by ELISA using a plate coated with a/3 (i-42) synthetic peptide (manufactured by Anaspec). Specifically, the A/3 (1 - 42) synthetic peptide dissolved in disulfoxide (DMSO) was diluted in distilled water and added to a 96-well plate (100 ng/weii) at 4 (: The coating was applied overnight (overnight), blocked with 1% Block ace (made by Xueyin Dairy Co., Ltd.), and the test sample 丨〇〇μί was added, and cultured in ye for 1 night. After the completion of the reaction, the plate was washed, and a horseradish peroxidase-conjugated anti-mouse immunoglobulin anti-35 201138815 (anti-mouse Ig-HRP, manufactured by Amersham) was added at a temperature of 4°. C was incubated for 2 hours. After the reaction is completed, it is washed with PBS, and a chromogenic substrate ABTS [2, 2, - oligo-indole-double (3-ethyl benzo-t; s-beta) _6-supply acid], (2, 2) is added. '-azino-bis(3-ethylbenzthiazoline)-6-sulphonic acid) (manufactured by KPL) After the incubation at room temperature for 30 minutes, the absorbance at 405 nm was measured. The anti-A/3 antibody was quantified using an anti-A/3 monoclonal antibody, and the anti-A (S antibody was quantified by a standard curve. The eight peptides evaluated all induced anti-A/3 antibody production by additional administration of the antibody. The amount is increased (Fig. 1). It can be seen that among them, RGD with GKK linker peptide - DiTox(19) - GKK - Α/3(1 - 15) has the highest anti-Α/3 antibody-producing ability '6 times After the additional administration, the known peptide is

RGD — DITOX ( 20 ) — Six times more anti-AjS antibodies were produced from KK-A|3 (1–13) (Figure 1 and Table 1). Other peptides with the GKK linker peptide were also significantly less resistant to A-antibody induction (Figure 1 and Table 丨). Further, rgD — DiTox ( 19 ) — VVKK — AjS ( 1-15) having a VVKK linker peptide also showed a higher anti-A antibody-inducing ability (Fig. i and Table 丨). The anti-A/3 antibody-induced ability of RgD-DiTox(19)_VKK-a Lu (1_15) was the same as that of RGD-DiTox (20) - ΚΚ-A/3 (13) (Fig. 1 and Table 1). On the other hand, a clear tendency was not found for the 8-cell epitope (Fig. 1). 36 201138815 Table 1 Comparison of anti-Αβ anti-dare love in blood in 6 times of Balb/c mice and RGD-DiTox (20) -ΚΚ-Αβ (1-13)璁According to the mean ±SE(pg/mL) and -KK-linker RGD-DiTox (20>ΚΚ-Λ ^ (1-13) 37.9 -t. 18.4 1.0 RGD-DiTox (19>VKK-A β ( L-15) 41.6 6.1 1.1 RGD-DiTox (19>-VVKK-A β (1-15) 108.1 50.0 2.9 RGD-DiTox (19)-GKK-A β (1-15) 236.9 ± 83.4 6.3 RGD-DiTox ( 19>GKK-A β (1-13) 173.2 104.6 4.6 RGD-DiTox (19>GKK-A β (1-10) 75.9 27.2 2.0 RGD-DiTox (19>GKK-A β (1-8) 112.4 Soil 19.1 3.0 RGD-DiTox (19)-GKK-A β (1-6) 145.0 Soil 100.1 3.8 From the above results, it is known that the amino acid sequence represented by GKK, VKK or VVKK is set by the amino acid sequence of the linker peptide. The acid sequence gives higher anti-Α/5 antibody-producing ability than the amino acid sequence represented by ΚΚ. Further, the amino acid sequence of the conjugated peptide is an amino group represented by GKK, VKK or V VKK. The acid sequence (8-peptide vaccine significantly enhances the production of antibodies due to additional administration. Yes, RGD — DiTox ( 19) — GKK — AjS ( 1 — 1 5 ) has a high anti-A/3 antibody-inducing ability and is considered to be effective as a peptide vaccine for the treatment of Alzheimer's disease. After the end of the additional administration, the withdrawal period of one month was followed, and the change in the amount of anti-Aj8 antibody in the blood caused by the withdrawal was observed. The amine having the one represented by GKK, VKK, and VVKK was administered. In the case of the peptide of the linker peptide composed of the acid sequence, the amount of the anti-Aj8 antibody in the blood is rapidly decreased after the additional administration is completed. On the other hand, the conventional peptide RGD-DiTox (20) is administered. _ KK - A Lu (1-13), the amount of anti-Aj8 antibody in the blood was not reduced, and was maintained for 1 month. [Example 2] Various A) 8-peptide vaccines were prepared, and JU mice were used to evaluate their resistance. A/5 antibody-induced ability. JU mice (Quon (Quon D.) et al., "Formation of beta-amyloid protein deposits in brains of transgenic mice", Nature (Nature), 1991, Vol. 352, ρ·239 — 241) It is used for breeding at home. The peptide is based on the link of the peptide peptide of RGD-DiTox (20)-ΚΚ-A/3 (1 - 13 ) (sequence number 12 in the sequence listing) of the peptide prototype developed in Patent Document 2 and And the b cell epitope region was changed and designed' and synthesized by external entrustment (Operon Biotechnologies Co., Ltd.). All peptides were dissolved in PBS in a manner of 丨mg/mL. The evaluated peptides are the following five species: RGD — DiTox ( 20 ) — KK — A^ ( 1 — 13) (sequence number i2 in the sequence listing), R〇D- DiTox( 19) —VKK — A/ 3 ( 1 — 1 5 ) (sequence number 1 3 in the sequence listing), RGD — DiTox ( 19) — VVKK—A pan (1–15) (sequence number 6 in the sequence listing) ' RGD — DiTox ( 19 ) — GKK — A/3 ( 1-15) (sequence number 7 in the sequence listing), RGD - DiTox ( 19 ) - GKK- Aj3 ( 1 - 13 ) (sequence number 8 in the sequence listing) The mouse system was carried out as follows. First, 5 〇 yL / mouse precipitated diphtheria tetanus mixed toxoid (manufactured by Kitakami Research Institute) was administered 38 201138815 to the back of 8 weeks of jujube mice for pre-immunization, and peptide administration was performed 2 weeks after immunization. . The peptide was prepared into 2〇〇/xg/mL, and mixed with an equal amount of adjuvant (Freund incomplete adjuvant (FIA)' and Wako Pure Chemical Co., Ltd.) to prepare an emulsion. 〇〇Mg/mouse (10 肫/mouse) was administered subcutaneously to the back of the JU mouse. After the first administration, one group (N) was used, and two additional doses were administered at intervals of two weeks. One week after the second additional injection, the blood was destroyed from the tail of the mouse. A protease inhibitor chicken tail wine (manufactured by Roche Diagnostics Co., Ltd.) was added to Jinzhongzhong as a test sample for anti-Aj8 antibody. Further, an emulsion was prepared by mixing with an equivalent amount of FIA of PBS, and administered to a subcutaneous skin as a negative control group at 100/xL/mouse. The amount of anti-A/5 antibody in blood was tested according to the same method as the anti-A/3 antibody amount test method described in Example 1. The five peptides evaluated were induced to produce anti-a/5 antibodies by two additional administrations (Table 2). RGD-DiT〇x(19)-GKK-A/5 (1-15) with GKK linker peptide has the highest anti-A cold antibody induction ability, and the known peptide RGD-DiTox (20) - KK-A/3 (1 -1 3 ) induced 85-fold anti-A /3 antibody production (Table 2). Also, similarly, RGD-DiTox(19)-GKK-A/3 (1-13) and RGD-DiTox (19)-VVKK-A/S (1-15) with GKK linker peptide also showed ratio RGD-DiTox(20)-KK-A million (1 - 13) was more than 10 times more resistant to A/8 antibody induction (Table 2). It was confirmed that the result by administration of the emulsion was also the same as that of the peptide solution. 39 201138815 Table 2 Anti-Αβ anti-sense love in blood of 2 times in JU mice, and comparison with RGD-DiTox (20) — KK-Ap (1-13) Anti-Αβ anti-璁曼-ΚΚ-远结子RGD-DiTox (20)-ΚΚ-Α /ί (l-»3) RGI>DiTox (19>VKK-A ί) (1-15) RGL>DiTox (19)-VVKK-A β (1 -15) RGD-DiTox (19)-GKK-A β (1-15) RGl>DiTox (19)-GKK-A /^(1-13) Comparison of ±SE(n^/mL) 11 1.0 39 3.5 177 16.1 937 85.2 124 11.3 From the above results, it can be seen that in the administration using an adjuvant, the amino acid sequence represented by GKK, VKK or VVKK is set by the amino acid sequence of the linker peptide. It is also possible to obtain an anti-Ay5 antibody-inducing ability higher than the amino acid sequence represented by KK. In particular, 1100-0(^(19)-GKK-AyS (1-15) has a high anti-A/3 antibody-inducing ability and is considered to be effective as a peptide vaccine for the treatment of Alzheimer's disease. [Example 3] Various A cold peptide vaccines were prepared, and Balb/c mice were used to evaluate the ability of each anti-A/? antibody to induce production. | Synthesis of RGD-DiTox (20) - KK-(1-13) (preface) The serial number in the list 12), RGD - DiTox (19) - VKK - A cold (1 - 13) (sequence number 43 in the sequence listing) 'and RGD - DiTox (19) - VVKK-A/5 (1 - 13) Three peptides (SEQ ID NO: 44 in the Sequence Listing) were each dissolved in PBS so as to be 1 mg/mL. 40 201138815 The administration of the peptide to the mouse was carried out as follows. First, 5〇 Predatory diphtheria and tetanus tetanus mixed toxoid (manufactured by Kitakami Research Institute) p Pre-immunization under the skin of the 6-week Balb/c mouse (Japan charles river Co., Ltd.) In the case of administration, a lmg/mL peptide solution of 5 〇/xL/mouse (50/^G/mouse) was administered to the peritoneal cavity, and group i (7) was used as 4 6 (negative control group 4, RGD - DiTox (19) - VVKK-A/3 (1 - 13) group 6 and 5 other peptide groups) 'after the initial administration, at intervals of two weeks 6 additional additions. After the injection of the peptide, the blood was collected from the tail of the mouse and the plasma component was taken. A protease inhibitor cocktail (manufactured by Roche Diagnostics Co., Ltd.) was added to the plasma as an anti-antibody test sample. Further, it was administered to the peritoneal cavity as a negative control group by PBS of 50 handsome/mouse. The test for the amount of anti-A antibody in blood was carried out by the EUSA method using a plate coated with a peptide (manufactured by Anaspec). Specifically, the Aj3 (i_42) synthetic peptide dissolved in dimethyl sulfoxide (DMS oxime) was diluted in distilled water, and added to a 96-well plate (1 ng/weil) and coated in 4C. . Blocking was carried out with 1% B1 〇ck Snow Seal Dairy Co., Ltd., and a test sample of 1 μμί was added at 4. 〇 1 night. After the completion of the reaction, the plate was washed, and the mixture was diluted for 2 times with a spicy, peroxidase-conjugated anti-mouse immunoglobulin antibody (anti-m can = -hrp' Amersham), and cultured at 4 t for 2 hours. After completion of the reaction, the cells were washed with PBS, and a chromogenic substrate ABTS (2, 2, azobis(3-ethylbenzothiazoline 6-sulfonic acid, manufactured by KpL) was added, and cultured at room temperature for 30 minutes at 201138815. Thereafter, the absorbance at 405 nm was measured. The anti-A/3 antibody was quantified using an anti-A/3 monoclonal antibody, and the anti-A/3 antibody was quantified by a standard curve. The three peptides evaluated all induced anti-A/3 antibody production, The amount of antibody added by additional administration was increased (Fig. 2). It was found that RGD-DiTox(19) - VVKK-A/3 (1 - 13 ) with VVKK linker peptide was produced after 6 additional administrations. The known peptide is RGD-DiTox (20) - KK - Aj8 (1 - 1 3 ), which is 3 times more anti-A (S antibody (Fig. 2 and Table 3). After 6 additional additions, it has a VKK linker. The anti-A/? antibody-producing ability of the peptide RGD-DiTox (19)-VKK-A/? (1-13) was 1.3 times that of RGD-DiTox (20) - KK-A/3 (1-13) ( Figure 2 and Table 3). Table 3

In the Balb/c mice, 6 times after the additional reference, the anti-Aβ anti-sputum in the blood and the RGD-DiTox (20)-ΚΚ-Αβ (1-13) were compared. :SE(comparison of n_g/mI〇 and -KK-linker RGD-DiTox(20)-KK-AM Bu 13) 26.6 5.3 1.0 RGD-DiTox(19)-VKK AiJ (M3) 33.6 Soil 11.8 1.3 RGD-DiTox (19)-VVKK-A^ (M3) 80. 1 Soil 23.0 3.0 From the above results, it can be seen that by using the amino acid sequence of the linker peptide as the amino acid sequence represented by VVKK, ΚΚ indicates that the amino acid sequence has a higher anti-Α/5 antibody-inducing ability. [Example 4] Various Aj3 peptide vaccines were prepared and evaluated using JU-Tg2576 mice. 42 201138815 The anti-A/? antibody-producing ability ^ Chuan-Tg2576 is a mouse obtained by reciprocating Tg2576 mice with ju mice. The JXj_ Tg2576 mouse is used for breeding at home. For RGD-DiTox(20) - KK-A0(1-13) (sequence number 12 in the sequence listing), the RGD of the T cell epitope is made into the reverse sequence - DiTox ( Rev) - KK- A] 8 ( 1 - 13 ) (sequence number 45 in the sequence listing), RGD - DiTox ( 19) - VKK- A/? ( 1 - 15) (sequence number 13 in the sequence listing), RGD-DiTox (19) - VVKK-A/3 (1-13) (sequence number 44 in the sequence listing), and rgD - DiT0x(19) - VVKK - A/3 (1_15) (sequence number 6 in the sequence listing) each become 1 mg The /mL method was dissolved in PBS. Various peptides were administered to mice as described below. First, pre-immunization was carried out by injecting the toxoid of the diphtheria and tetanus tetanus (made by Kitakami Institute) into the back of the 3-month-old JU-Tg2576 mouse, and the peptide was administered 2 weeks after the immunization. Give. The peptide was prepared into lrng/mL, and mixed with an equal amount of adjuvant (Fruin Incomplete Adjuvant (FIA), manufactured by Wako Pure Chemical Co., Ltd.) to prepare an emulsion to 100 μL/mouse (50 pg/mouse). ) was administered to the abdominal cavity of the JU-Tg2576 mouse. 1 group (N) is 9-20 (negative control group 20, RGD-DiTox (20) -KK-Aj8 (1-13) group Π only ' RGD - DiTox ( 19 ) — VVKK — Aj3 ( 1 — 13) Group 11 only, RGD - DiTox ( 19) - VKK- Aj8 ( 1 _ 15 ) group and RGD - DiTox (19) - VVKK- AjS (l-15) group 10, RGD - DiTox ( Rev) — KK -A/3 (1-13) Group 9), after the initial administration, 6 additional additions were made at intervals of 2 weeks. One week after the administration of the peptide, blood was collected from the mouse tail 43 201138815, and plasma components were taken. A protease inhibitor cocktail (manufactured by Roche Diagnostics Co., Ltd.) was added to blood 喈 water τ as a sample for anti-a-antibody test. Further, an emulsion of FT Δ equivalent to PBS and FIA of 丨 1 was mixed to prepare an emulsion, and 1 ΟΟμί/mouse was administered to the abdominal cavity as a negative control group. The test for the amount of the anti-cold antibody in the blood was carried out by the EUSa method using a plate coated with a synthetic peptide (i-42) synthetic peptide (manufactured by Anaspec). Specifically, 80,000 (1,4, the synthetic peptide dissolved in dimethyl sulfoxide (DMS oxime) was diluted in distilled water and added to a 96-well plate (1 ng/weU) at 4°. 1 night was applied to C. The block was blocked with i% Block ace (manufactured by Xueyin Dairy Co., Ltd.), and the test sample was added with 1 liter of L and cultured for 1 night at 4 C. After the reaction, Wash the plate and add 2 〇〇〇 times of horseradish peroxidase-conjugated anti-mouse immunoglobulin antibody (anti-mouse IG-HRP, manufactured by Amersham), and incubate for 2 hours at 4. Washed with PBS, and added a chromogenic substrate a BTS (2,2 - azo-mono-(3-ethylbenzothiazoline)-6-sulfonic acid, manufactured by KPL) 'cultivate at room temperature 3 0 After a minute, the absorbance at 40 nm was tested. Anti-A/5 antibody was quantified using an anti-A/3 monoclonal antibody, and the anti-A cold antibody was quantified from a standard curve. The T cell epitope was made into a reverse sequence. R (GD — DiTox (Rev ) — KK — A卩 (1 — 1 3 ), its anti-antibody production is not induced (Fig. 3). The other four wins All of them were induced to produce anti-a/3 antibody, and the amount of antibody was increased by additional administration (Fig. 3). It can be seen that RGD-DiTox (19) — VKK-A/? (1—with VKK linker peptide 15) After 6 additional additions, the performance is also better than the known peptide RGD — 44 201138815

DiTox ( 20) — KK—AjS ( 1–13) high anti-A/? antibody (Figure 3 and Table 4). Other peptides with VVKK linker peptides also showed higher anti-A/3 antibody-inducing ability (Figure 3 and Table 4). Table 4 Anti-Aβ anti-sputum in blood of 6-times of additional administration in JU-Tg2576 mice and comparison with RGD-DiTox (.20)-ΚΚ-Αβ (1-13) Love is iSE〇tg/mL) Compared with the ruler-linker RGD-DiTox(20)-KK-A β (1-13) 22.9 ± 6.7 1.0 RGD-DiTox(Rev)-KK-A0 (1- 13) 4. 7 ± 0.8 0.2 RGD-DiTox ((9)-VKK-A0 (Bu 15) 54. 7 Soil 19. 1 2.4 RGD-DiTox(l9)-VVKK-A0 (1-13) 61.0 Soil 23.9 2. 7 RGD-DiTox(l9)-WKK-A^ (1-15) 42. 1 ± 20.4 1.8 From the above results, it is known that the amino acid sequence represented by VKK or VVKK is set by the amino acid sequence of the linker peptide. The sequence can also give higher anti-Α/3 antibody-producing ability than the amino acid sequence represented by ΚΚ. Further, the amino acid sequence of the conjugated peptide is an amino acid sequence represented by VKK or VVKK. The smectic peptide vaccine significantly enhances the production of the antibody by the additional administration. [Industrial Applicability] As described above, the present invention provides a peptide and a composition containing the peptide as an active ingredient, The peptide is characterized by: containing immunity in the living body Recalling the amino acid sequence (T) of the amino acid sequence of the T cell epitope, and the amino acid sequence of the amino acid sequence of the specific one or more B cell epitopes containing the antigen (B) And a linker that is disposed between the above T and the above B so as to be connected to each other. 45 I: : 201138815 m acid: 'The amino acid sequence of the linker peptide is gkk, νκκ or ' The present invention provides a winning form having the above-described knot-inducing ability and a therapeutic composition containing the winning form as an effective ingredient: the peptide of the present invention is widely restricted by the human-type (10) single body type Many humans, especially those who constitute immune memory by vaccination, can be used as an effective peptide vaccine for preventing and treating various diseases caused by foreign substances such as pathogenic bacteria and viruses. The antibody production of w, which is effective in preventing and treating various diseases such as neurodegenerative diseases including Alzheimer's disease. Further, the peptide vaccine of the present invention shows an inducing antibody even without using an immunological adjuvant. Generating ability Further, it can be administered by nasal administration or oral administration, etc., and further, the blood/agronomic degree of the antibody is rapidly decreased after the administration, so that it is a simple and safe peptide vaccine. 46 201138815 [ Sequence text arbitrary text (Free Text)] Serial number 1: Class powder protein / 3 wins 1 - 42. SEQ ID NO: 2: Amyloid-like Lusheng peptide 1-40. Sequence number 3: synthetic peptide. SEQ ID NO: 4: A peptide consisting of amino acid residues 1 _ 15 of the amyloid-like peptide. SEQ ID NO: 5: A peptide consisting of amino acid residues 1 _ 丨 3 of the amyloid-like peptide. SEQ ID NO: 6: Synthetic peptide, here referred to as rgd - DiT 〇 x (1 9 ) - VVKK - A / 3 (1 - 15). SEQ ID NO: 7. Synthetic peptide, here referred to as rg d - DiTox (1 9 ) - GKK - AjS (1 - 1 5 ). SEQ ID NO: 8: Synthetic peptide, here referred to as rgd-DiT〇X(19) - GKK-A/3 (1 - 1 3 ). SEQ ID NO: 9: Synthetic peptide, here referred to as DiTox (19) - GKK-AjS (1 - 1 〇). Sequence number 1 〇 · Synthetic peptide, here referred to as RGD _ DiT〇x (丨9) _ GKK - A/5 (1 - 8). SEQ ID NO: 11: Synthetic peptide GKK- Αβ (1 - 6). Serial number Ma 1 2: Synthetic wins ΚΚ- Α/5 (1 ~~ 13). SEQ ID NO: 1 3: Synthetic peptide VKK - Α卢(1 - 15 ) 〇, referred to herein as RGD - DiTox ( 19 ) - , referred to herein as RGD - DiTox ( 20) - referred to herein as RGD-DiTox (19)- 47 201138815 Sequence number 14: The peptide formed. SEQ ID NO: 15: The peptide formed. Serial number 16: The winning form. Sequence number Π : The peptide formed. Sequence number 18 = the peptide. SEQ ID NO: 19: The peptide. Serial number 20: Serial number 21: Serial number 2 2 · Serial number 23 = Serial number 24 = Serial number 25 = Serial number 26 = Serial number 27 = Serial number 2 8 : Serial number 29: Serial number 3 0 · Serial number 3 1 : 1 - 11 The amino acid residue of the peptide-like peptide of the peptide is composed of the amino acid of the amyloid/3 peptide and the amino acid of the peptide of the peptide Residue 3 _丨5 is based on the amino acid residue of the peptide powder 0 peptide, 1 〇 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由Part of the peptide of the diphtheria toxoid of the amino acid residue 1 to 6 of the peptide. Part of the peptide of the diphtheria toxoid. Part of the peptide of the diphtheria toxoid. Part of the peptide of tetanus toxoid. Part of the peptide of tetanus toxoid. Part of the peptide of tetanus toxoid. Part of the peptide of tetanus toxoid. Part of the peptide of tetanus toxoid. Part of the peptide of tetanus toxoid. Part of the peptide of tetanus toxoid. Part of the peptide of tetanus toxoid. Part of the peptide of tetanus toxoid. 48 201138815 Serial number 32: Serial number 33: Partial peptide. Sequence number 34: Partial peptide. Serial number 3 5 : Partial peptide. SEQ ID NO: 36: Partial peptides SEQ ID NO: 37: Peptide. Serial number 3 8 Serial number 39 Serial number 40 Serial number 41 Serial number 42 Serial number 43 VKK- Αβ (1 Sequence number 44 VVKK- Αβ (SEQ ID NO: 45: ΚΚ- A|3 (1 - Part of the peptide of tetanus toxoid) Human type / bovine tuberculosis secretory protein ΜΡΤ 64 human type / bovine tuberculosis secretory protein ΜΡΤ 64 human type / bovine tuberculosis secretory protein ΜΡΤ 64 human type / bovine tuberculosis secretory protein ΜΡΤ 64 contains The cell adductive cell (Cell Adhesive Motif) comprises a cell followed by a peptide of a motif. A peptide comprising a cell followed by a motif. A peptide comprising a cell followed by a motif. A peptide comprising a cell followed by a motif. The peptide of the motif: Synthetic peptide, here called RGD - DiTox (1 9 )- _ 13 ) 〇: Synthetic peptide, here called RGD-DiTox ( 19) - 1 - 13 ). Peptide, referred to herein as RGD — DiTox ( Rev )— 13)° 49 201138815 [Simplified Schematic] Figure 1 shows the use of Balb/c mice to evaluate anti-AjS antibodies after additional administration of various eight-Lucop peptide vaccines. Induction ability Results Figure. The evaluation was carried out using a group of 4 mice, and the anti-A/5 antibody amount was expressed by the average S.E. All the peptides tested have a cell-binding motif with a cell adhesion molecule at the N-terminus, that is, an amino acid sequence represented by RGD, and then have the following structure in which the amino acid sequence is sequentially linked: containing the diphtheria-derived class The amino acid sequence of the amino acid sequence of the T cell epitope of the toxin (hereinafter, abbreviated as "DiTox"), the amino acid sequence of the linker peptide, and the b cell derived from the A/3 peptide The amino acid sequence of the amino acid sequence of the epitope. Among the eight peptides evaluated, RGD-DiTox (19) - GKK having a linker peptide (hereinafter, abbreviated as "GKK linker peptide") composed of an amino acid sequence represented by GKK - A/5 (1 - 15) showed the highest anti-A/3 antibody-inducing ability, and an increase in the production of A-lu antibody was also observed after 6 additional administrations. Other peptides having a GKK linker peptide also showed higher anti-AjS antibody-inducing ability. Further, RGD-DiTox(19)-VVKK-A/3 (1-15) having a linker peptide (hereinafter, abbreviated as "VVKK linker peptide") composed of an amino acid sequence represented by VVKK ) also showed higher anti-a/5 antibody-inducing ability. The "Veh" in the figure indicates the result of administration of phosphate-buffered physiological saline (Pbs) instead of AjS peptide vaccine. (Example 1). Fig. 2 is a graph showing the results of evaluation of anti-antibody-inducing ability after additional administration of various a/3 win vaccines using Baib/c mice. In the figure, "Vehlcle" indicates the result of administration of phosphate buffered physiological saline (PBS) instead of A/3 win 50 201138815 vaccine. "KK1-13" indicates RGD_DiT〇x ()KK A/3 ( 1 - 13 ). "VKK1 - 13" means RGD-DiTox

(19) VKK~~A0(i-13)〇“vVKK1-13” indicates RGD

DiTox Example 3) (19) ~VVKK-A/3(1-13)° (Figure 3: shows the use of ju-Tgh% mice to evaluate the anti-antibody induction ability after additional administration of various A-Luculin peptide vaccines The results are shown in the figure. "Vehicle" in the figure indicates the result of administration of phosphate-buffered physiological saline (pBS) instead of a blister peptide. r Tcell rev" indicates RGD-DiT〇x (Rev) - KK — A/5( 1 — 13 ). “KK1-13” means rgd—DiTox (20)—KK—A/3 (1–13). “VKK1—15” means RCJD-DiT〇X (19) —VKK-A/3(1-15)c“VVKK1—13” means RGD —DiTox ( 19 ) — VVKK — A/3 ( 1_ 13)° “VVKK1—15” means RGD — DiTox ( 19 ) — VVKK — A (1 — i 5 ). (Example 4) Figure 4 is a diagram showing the amino acid sequence and sequence number of various peptides. Ι:ϊ 51 201138815 [Sequence Table]

SEQUENCE LISTING <110> Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo DAIICHI SANKYO COMPANY, LTD. <120> peptide vaccine

<130> GP10-1032TW <150> JPP2010-010953 <151> 2010-01-21 <160> 45 <170> Patentln version 3.1 <210> 1 <211>

<212> PRT <213> Homo sapiens <220><221>misc_feature<223> amyloid beta peptide 1 -42 <400>

Asp Ala Glu Phe Arg His Asp Ser Gly Tyr Glu Val His His Gin Lys 15 10 15

Leu Val Phe Phe Ala Glu Asp Val Gly Ser Asn Lys Gly Ala lie lie 20 25 30

Gly Leu Met Val Gly Gly Val Val lie Ala 35 40 <210> 2 1 201138815 <211〉 40

<212> PRT <213 > Homo sapiens <220><221> misc-feature <223> amyloid beta peptide 1-40 <400> 2

Asp Ala Glu Phe Arg His Asp Ser Gly Tyr Glu Val His His Gin Lys 1 5 10 15

Leu Val Phe Phe Ala Glu Asp Val Gly Ser Asn Lys Gly Ala lie lie 20 25 30

Gly Leu Met Val Gly Gly Val Val 35 40

<210> 3 <211> 4 <212> PRT <213> Artificial Sequence <220>

<223> a synthetic peptide <400> 3 Val Val Lys Lys <210> 4 <211> 15 <212> PRT <213> Artificial Sequence <220> 201138815 <223>a polypeptide consisting of Amino acid residues 1-15 of amyloid beta peptide <400> 4

Asp Ala Glu Phe Arg His Asp Ser Gly Tyr Glu Val His His Gin 15 10 15 <210> 5 <211> 13 <212> PRT <213> Artificial Sequence <220><223>a polypeptide consisting Of amino acid residues 1-13 of amyloid beta peptide <400> 5

Asp Ala Glu Phe Arg His Asp Ser Gly Tyr Glu Val His 1 5 10 <210> 6 <211> 41 <212> PRT <213> Artificial Sequence <220><223> a synthetic peptide, herein Called RGD-DiTox( 19)-WKK-Abeta( 1-15) <400> 6

Arg Gly Asp Ala Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin 15 10 15

Val Val His Asn Ser Tyr Val Val Lys Lys Asp Ala Glu Phe Arg His 20 25 30 3 201138815

Asp Ser Gly Tyr Glu Val His His Gin 35 40

<210> 7 <211> 40 <212> PRT <213> Artificial Sequence <220><223> a synthetic peptide, herein called RGD-DiTox(19)-GKK-Abeta(1-15) <400> 7

Arg Gly Asp Ala Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin 15 10 15

Val Val His Asn Ser Tyr Gly Lys Lys Asp Ala Glu Phe Arg His Asp 20 25 30

Ser Gly Tyr Glu Val His His Gin 35 40

<210> 8 <211> 38 <212> PRT <213> Artificial Sequence <220><223> a synthetic peptide, herein called RGD-DiTox(19)-GKK-Abeta(ll 3) <;400> 8

Arg Gly Asp Ala Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin 15 10 15

Val Val His Asn Ser Tyr Gly Lys Lys Asp Ala Glu Phe Arg His Asp 20 25 30 4 201138815

Ser Gly Tyr Glu Val His 35

<210> 9 <211> 35 <212> PRT <213> Artificial Sequence <220><223> a synthetic peptide, herein called RGD-DiTox(l 9)-GKK-Abeta(l-10 ) <400> 9

Arg Gly Asp Ala Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin 15 10 15

Val Val His Asn Ser Tyr Gly Lys Lys Asp Ala Glu Phe Arg His Asp 20 25 30

Ser Gly Tyr 35 <210> 10 <211> 33 <212> PRT <213> Artificial Sequence <220><223> a synthetic peptide, herein called RGD-DiTox(19)-GKK-Abeta( 1-8) <400> 10

Arg Gly Asp Ala Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin 15 10 15

Val Val His Asn Ser Tyr Gly Lys Lys Asp Ala Glu Phe Arg His Asp 20 25 30 5 201138815

Ser

<210> 11 <211> 31 <212> PRT <213>Artificial Sequence <220><223>a synthetic peptide, herein called RGD-DiTox(19)-GKK-Abeta(1-6) <400> 11

Arg Gly Asp Ala Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin 15 10 15

Val Val His Asn Ser Tyr Gly Lys Lys Asp Ala Glu Phe Arg His 20 25 30

<210> 12 <211> 38 <212> PRT <213> Artificial Sequence <220><223>a synthetic peptide, herein called RGD-DiTox(20)-KK-Abeta(1 -13) <400〉 12

Arg Gly Asp Ala Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin 15 10 15

Val Val His Asn Ser Tyr Asn Lys Lys Asp Ala Glu Phe Arg His Asp 20 25 30

Ser Gly Tyr Glu Val His 201138815 35

<210> 13 <211> 40 <212> PRT <213> Artificial Sequence <220><223> a synthetic peptide, herein called RGD-DiTox(19)-VKK-Abeta( 1-15) <400〉 13

Arg Gly Asp Ala Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin 15 10 15

Val Val His Asn Ser Tyr Val Lys Lys Asp Ala Glu Phe Arg His Asp 20 25 30

Ser Gly Tyr Glu Val His His Gin 35 40

<210> 14 <211> 11 <212> PRT <213> Artificial Sequence <220><223> a polypeptide consisting of amino acid residues 1-11 of amyloid beta peptide <400>

Asp Ala Glu Phe Arg His Asp Ser Gly Tyr Glu 1 5 10 <210> 15 <211> 9 <212> PRT 201138815 <213> Artificial Sequence <220><223> a polypeptide consisting of amino acid Resins 3-11 of amyloid beta peptide <400> 15

Glu Phe Arg His Asp Ser Gly Tyr Glu 1 5

<210> 16 <211> 13 <212> PRT <213> Artificial Sequence <220><223> a polypeptide consisting of amino acid residues 3-15 of amyloid beta peptide <400>

Glu Phe Arg His Asp Ser Gly Tyr Glu Val His His Gin 1 5 10

<210> 17 <211> 10 <212> PRT <213> Artificial Sequence <220><223> a polypeptide consisting of amino acid residues 1-10 of amyloid beta peptide <400>

Asp Ala Glu Phe Arg His Asp Ser Gly Tyr 1 5 10 <210> 18 201138815

<211>8 <212> PRT <213> Artificial Sequence <220><223> a polypeptide consisting of amino acid residues 1-8 of amyloid beta peptide <400>

Asp Ala Glu Phe Arg His Asp Ser 1 5 <210> 19 <211> 6 <212> PRT <213>Artificial Sequence <220><223> a polypeptide consisting of amino acid residues 1-6 of Amyloid beta peptide <400> 19

Asp Ala Glu Phe Arg His 1 5

<210> 20 <211> 20 <212> PRT <213> Artificial Sequence <220><223> a partial peptide of diphtheria toxoid <400> 20

Ala Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin Val Val His 15 10 15 9 201138815

Asn Ser Tyr Asn 20

<210> 21 <211> 19 <212> PRT <213> Artificial Sequence <220><223> a partial peptide of diphtheria toxoid <400> 21

Ala Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin Val Val His 1 5 10 15

Asn Ser Tyr

<210> 22 <211> 19 <212> PRT <213> Artificial Sequence <220><223> a partial peptide of diphtheria toxoid <400> 22

Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin Val Val His Asn 1 5 10 15

Ser Tyr Asn

<210> 23 <211> 16 <212> PRT 201138815 <213> Artificial Sequence <220><223> a partial peptide of tetanus toxoid <400> 23

Leu Gin Thr Met Val Lys Leu Phe Asn Arg lie Lys Asn Asn Val Ala 15 10 15

<210> 24 <211> 18 <212> PRT <213> Artificial Sequence <220><223> a partial peptide of tetanus toxoid <400>

Phe Leu Gin Thr Met Val Lys Leu Phe Asn Arg lie Lys Asn Asn Val 15 10 15

Ala Gly

<210> 25 <211> 16 <212> PRT <213> Artificial Sequence <220><223> a partial peptide of tetanus toxoid <400> 25 lie His Val Leu His Gly Leu Tyr Gly Met Gin Val Ser Ser His Glu 15 10 15 201138815

<210> 26 <211> 18 <212> PRT <213> Artificial Sequence <220><223> a partial peptide of tetanus toxoid <400>

Leu lie His Val Leu His Gly Leu Tyr Gly Met Gin Val Ser Ser His 15 10 15

Glu lie

<210> 27 <211> 18 <212> PRT <213> Artificial Sequence <220><223> a partial peptide of tetanus toxoid <400>

Tyr lie Val Asn Glu Asp Lys Phe Gin lie Leu Tyr Asn Ser lie Met 15 10 15

Tyr Gly

<210> 28 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> a partial peptide of tetanus toxoid 12 201138815 <400> 28

Gin Tyr lie Val Asn Glu Asp Lys Phe Gin lie Leu Tyr Asn Ser lie 15 10 15

Met Tyr Gly Phe 20

<210> 29 <211> 15 <212> PRT <213> Artificial Sequence <220><223> a partial peptide of tetanus toxoid <400> 29

Ser Tyr Gin Met Tyr Arg Ser Leu Glu Tyr Gin Val Asp Ala lie 15 10 15

<210> 30 <211> 16 <212>PRT <213> Artificial Sequence <220><223> a partial peptide of tetanus toxoid <400> 30

Arg Ser Tyr Gin Met Tyr Arg Ser Leu Glu Tyr Gin Val Asp Ala lie 15 10 15

<210> 31 <211> 15 <212> PRT <213> Artificial Sequence 13 201138815 <220> <223> a partial peptide of tetanus toxoid <400> 31

Asn lie Asn lie Phe Met Arg Glu Ser Ser Arg Ser Phe Leu Val 15 10 15 <210> 32 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> a partial peptide Of tetanus toxoid <400〉 32 lie Asn lie Asn lie Phe Met Arg Glu Ser Ser Arg Ser Phe Leu Val 15 10 15

Asn

<210> 33 <211> 18 <212>PRT <213> Artificial Sequence <220> <223> a partial peptide of mycobacterium tuberculosis/bovis secreted protein MPT64 <400> 33

Met Ser Asp Pro Ala Tyr Asn lie Asn lie Ser Leu Pro Ser Tyr Tyr 15 10 15 14 201138815

Pro Asp

<210> 34 <211> 16 <212> PRT <213> Artificial Sequence <220> Secreted <223> a partial peptide of mycobacterium tuberculosis/bovis protein MPT64 <400> 34 lie Gin Met Ser Asp Pro Ala Tyr Asn lie Asn lie Ser Leu Pro Ser 15 10 15

<210> 35 <211> 16 <212> PRT <213> Artificial Sequence <220> Secreted <223> a partial peptide of mycobacterium tuberculosis/bovis protein MPT64 <400> 35

Asp Pro Ala Tyr Asn lie Asn lie Ser Leu Pro Ser Tyr Tyr Pro Asp 1 5 10 15

<210> 36 <211> 16 <212> PRT <213> Artificial Sequence <220> Secreted <223> a partial peptide of mycobacterium tuberculosis/bovis protein MPT64 15 201138815 <400>

Tyr Asn lie Asn lie Ser Leu Pro Ser Tyr Tyr Pro Asp Gin Lys Ser 15 10 15 <210> 37 <211> 5 <212> PRT <213> Artificial Sequence <220><223> a peptide Containing a cell adhesion motif <400> 37

Pro His Ser Arg Asn 1 5 <210> 38 <211> 4 <212> PRT <213> Artificial Sequence <220><223> a peptide containing a cell adhesion motif <400> 38 Asp Gly Glu Ala 1 <210> 39 <211> 5 <212> PRT <213> Artificial Sequence <220><223> a peptide containing a cell adhesion motif <400> 39 16 201138815

Tyr lie Gly Ser Arg 1 5 <210> 40 <211> 5 <212> PRT <213> Artificial Sequence <220><223> a peptide containing a cell adhesion motif <400> 40 lie Lys Val Ala Val 1 5 <210> 41 <211> 8 <212> PRT <213> Artificial Sequence <220><223> a peptide containing a cell adhesion motif <400> 41 Arg Phe Tyr Val Val Met Trp Lys 1 5 <210> 42 <211> 5 <212> PRT <213> Artificial Sequence <220><223> a peptide containing a cell adhesion motif <400 42 17 201138815 lie Arg Val Val Met 1 5

<210> 43 <211> 38 <212> PRT <213> Artificial Sequence <220><223> a synthetic peptide, herein called RGD-DiTox(19)-VKK-Abeta(1-13) <400> 43

Arg Gly Asp Ala Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin 15 10 15

Val Val His Asn Ser Tyr Val Lys Lys Asp Ala Glu Phe Arg His Asp 20 25 30

Ser Gly Tyr Glu Val His 35

<210> 44 <211> 39 <212>PRT <213> Artificial Sequence <220><223> a synthetic peptide, herein called RGD-DiTox(19)-VVKK-Abeta(1-13) <4〇〇> 44

Arg Gly Asp Ala Tyr Asn Phe Val Glu Ser lie lie Asn Leu Phe Gin 15 10 15

Val Val His Asn Ser Tyr Val Val Lys Lys Asp Ala Glu Phe Arg His 20 25 30 18 201138815

Asp Ser Gly Tyr Glu Val His 35

<210> 45 <211> 38 <212> PRT <213> Artificial Sequence <220><223> a synthetic peptide, herein called RGD-DiTox(Rev)-KK-Abeta( 1-13) <400〉 45

Arg Gly Asp Asn Tyr Ser Asn His Val Val Gin Phe Leu Asn lie lie 15 10 15

Ser Glu Val Phe Asn Tyr Ala Lys Lys Asp Ala Glu Phe Arg His Asp 20 25 30

Ser Gly Tyr Glu Val His 35 19

Claims (1)

201138815, VII. Patent application scope: 1. A peptide or a salt thereof, which has an amino acid sequence represented by the following formula, R1-T-R2-L-R3-B-R4 where T is represented An amino acid sequence containing an amino acid sequence constituting a T cell epitope of immunological memory, L is an amino acid sequence of a linker peptide, and B is a specific one or more B cells containing an antigen. The amino acid sequence of the amino acid sequence of the epitope, at least one of R1, R2, R3 and R4 is an amino acid sequence representing a cell binding motif of a cell adhesion molecule; wherein 'the linker peptide The amino acid sequence is an amino acid sequence represented by GKK, VKK or VVKK. 2. The peptide of claim 1 or a salt thereof, wherein the T cell epitope is derived from one of peptides selected from the group consisting of antigens for vaccination against diphtheria, tuberculosis, tetanus, and whooping cough or The amino acid sequence of two or more peptides. 3. The peptide or a salt thereof according to claim 1 or 2, wherein the B cell epitope is an amino acid sequence having an amino acid sequence comprising a B cell epitope of the A/5 peptide. 4. The peptide of claim 3 or a salt thereof, wherein the amino acid sequence of the B cell epitope comprising the Αβ peptide is the first amino acid from the n-terminus of A/3 to the first 15 amino acid sequences (SEQ ID NO: 4 in the Sequence Listing), or the first amino acid from the apical end of AjS to the 13 201138815 amino acid sequence (SEQ ID NO: 5 in the Sequence Listing). 5. A peptide or a salt thereof according to item 4 of the patent application, which is composed of an amino acid sequence selected from any one of SEQ ID NOs: 6 to 11, 13, 43 and 44 in the Sequence Listing. A peptide or a salt thereof, which is composed of an amino acid sequence selected from any one of Sequence Nos. 6 to 11, 丨3, 43 and 44 in the Sequence Listing. 7. A peptide or a salt thereof, which is composed of the amino acid sequence of the sequence number in the sequence listing. 8. A peptide or a salt thereof, which consists of the amino acid sequence of SEQ ID NO: 7 in the Sequence Listing. A peptide or a salt thereof which is composed of the amino acid sequence of SEQ ID NO: 8 in the Sequence Listing. 1 〇. A peptide or a salt thereof, which is composed of the amino acid sequence of SEQ ID NO: 9 in the Sequence Listing. A peptide or a salt thereof, which comprises an amino acid sequence of SEQ ID NO: 10 in the Sequence Listing. 2. A peptide or a salt thereof, which consists of the amino acid sequence of SEQ ID NO: 11 in the Sequence Listing. The 13'-type peptide or a salt thereof is composed of the amino acid sequence of SEQ ID NO: 13 in the Sequence Listing. • A peptide or a purine thereof consisting of the amino acid sequence of SEQ ID NO: 43 in the Sequence Listing. 15. - A peptide or its target, which is composed of the amino acid sequence of SEQ ID NO: 44 in the Sequence Listing. 2 201138815 16. A pharmaceutical composition comprising as an active ingredient a peptide selected from at least one of claims 1 to 15 or a pharmacologically acceptable salt thereof. 17. The pharmaceutical composition according to claim 16, wherein the pharmaceutical composition is further contained in one or more preparations. A pharmaceutical composition capable of inducing the production of an antibody against A/3, comprising the peptide of any one of claims 3 to 15 or a pharmacologically acceptable salt thereof, and one or more preparations Allowable additives for formulation. I. The pharmaceutical composition according to any one of claims 16 to 18, which is for use in the prevention and/or treatment of a disease caused by the treatment. 2. The pharmaceutical composition according to any one of claims 16 to 18, which is for use in the prevention and/or treatment of a disease selected from the group consisting of A U, Alheimer 5L Alzheimer's disease, mild cognition At least one disease of the disorder, Alzheimer's disease, Down's syndrome, and powder-like degeneration of the hall. For example, in the scope of patent application Nos. 16 to 18, , , , and only - are used to prevent and/or treat Alzheimer's disease. The 22 kinds of DNA's are the peptides of any one of the first to third aspects of the patent application.