Peptide conjugate vaccine compositions and methods for treating alzheimer's disease

Abstract

The present invention provides compositions and methods for treating diseases associated with amyloid deposits of Aβ in the brain of a patient, such as Alzheimer's disease. Such methods entail administering a pharmaceutical composition comprising an immunogenic fragment of Aβ capable of inducing a beneficial immune response in the form of an antibody to Aβ. The immunogenic fragment comprises a linear or multivalent peptide of Aβ. The pharmaceutical composition comprises the immunogenic fragment chemically linked to a carrier molecule, which can be administered with an adjuvant.

Description

Cross-references to related applications

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 599,885, filed November 16, 2023, the entire contents of which are incorporated herein by reference. Refer to the electronically submitted sequence list

[0002] This application contains a sequence list that has been electronically submitted in XML format, the entire contents of which are incorporated herein by reference. The XML file was created on October 1, 2024, named 25864-WO-PCT_SL.xml, and is 59,964 bytes in size. Invention Field

[0003] This disclosure generally relates to peptide-based pharmaceutical compositions and conjugate vaccines, and methods of using said compositions and vaccines for the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease. Background Technology

[0004] Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by dementia and pathological changes in the brain, including the accumulation of amyloid plaques and neurofibrillary tangles. JA Hardy, et al Alzheimer's Disease: the amyloid cascade hypothesis. Science (1992) 256:184-185. According to the "amyloid cascade hypothesis," increased accumulation of amyloid β (Aβ) peptide in the brain leads to the formation of Aβ oligomers and plaques, resulting in neurite lesion damage, neurofibrillary tangles formation, neuronal cell death, and cognitive decline. JA Hardy, et al ., The amyloid hypothesis of Alzheimer's Disease: progress and problems on the road to therapeutics. Science (2002) 297:353-356.

[0005] The Aβ peptide consists of a 40-42 amino acid sequence derived from amyloid precursor protein (APP). The N-terminal truncated form of Aβ... pE3 It is from Aβ 1-42 It is produced by the cyclization of the two N-terminal amino acids and the glutamic acid side chain, forming pyroglutamic acid. (T. Iwatsubo) et al., Full-length amyloid-beta (1-42(43)) and amino-terminallymodified and truncated amyloid-beta 42(43) deposit in diffuse plaques. Am JPathol. (1996) 149(6):1823-30. Aβ pE3 Peptides have a high tendency to aggregate, and accumulate early in the formation of amyloid cascades in plaque formation. TC Saido, et al ., Dominant and differential deposition of distinct beta-amyloid peptide species, Aβ N3(pE), in senile plaques. Neuron (1995) 14:457-466. T. Iwatsubo, et al ., Full-length amyloid-beta (1-42(43)) andamino-terminally modified and truncated amyloid-beta 42(43) deposit indiffuse plaques. Am. J. Pathol. (1996) 149:1823-1830. YM Kuo, et al .,Isolation, chemical characterization, and quantitation of Aβ 3-pyroglutamylpeptide from neuritic plaques and vascular amyloid deposits. Biochem.Biophys. Res. Commun., (1997) 237:188-191. S. Schilling, et al ., On the seeding and oligomerization of pGlu-amyloid peptides (in vitro). Biochemistry (2006) 45:12393-12399. Z. Schlenzig, et al., Pyroglutamate formation influences solubility and amyloidogenicity of amyloid peptides. Biochemistry (2009) 48:7072-7078.

[0006] Clearance of Aβ plaques has been presumed as a means of slowing the progression of Alzheimer's disease (AD), and in clinical trials, targeting Aβ has been shown to be effective. pE3 Passive immunotherapy has been shown to clear plaques and slow cognitive decline. (JR Sims) et al Donanemab inearly symptomatic Alzheimer Disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA. (2023) 330(6):512–527. Active immunotherapy (i.e., vaccine) has also been tested for the treatment of Alzheimer's disease. F. Mantile, et al Vaccination against β-amyloid as a strategy for the prevention of Alzheimer's Disease. Biology (Basel). (2020)9(12):425. Vaccination against β-amyloid was tested in a phase II clinical trial. 1-42 The candidate vaccine AN1792, formulated with QS-21 adjuvant, showed evidence of post-mortem plaque reduction. However, AN1792 induced meningoencephalitis in a subset of patients, attributed to a T-cell response to the vaccine. (JAR Nicoll) et al. , Persistent neuropathological effects 14 years following amyloid-β immunization in Alzheimer's Disease. Brain (2019) 142(7):2113–2126.

[0007] Currently, there are no specific and highly effective preventative or therapeutic treatments for Alzheimer's disease. Therefore, there is a strong need for alternative treatment measures. Invention Overview

[0008] The object of this invention is to provide pharmaceutical compositions for the preventive and therapeutic treatment of Alzheimer's disease. In particular, various aspects of the invention provide Alzheimer's disease vaccines that can be administered to mammals for the prevention and / or treatment of Alzheimer's disease.

[0009] This disclosure provides compositions and methods for treating diseases associated with Aβ amyloid deposits in the brain, such as Alzheimer's disease. In one aspect, this disclosure provides pharmaceutical compositions comprising an immunogenic peptide of at least six consecutive amino acids of SEQ ID NO: 1 and an immunogenic carrier protein.

[0010] In some embodiments, the immunogenic peptide is missing 1-10 amino acids at the N-terminus or 1-33 amino acids at the C-terminus of SEQ ID NO: 1. In other embodiments, the immunogenic peptide is missing 1-10 amino acids at the N-terminus and 1-33 amino acids at the C-terminus of SEQ ID NO: 1.

[0011] In some embodiments, the immunogenic peptide comprises at least 10 consecutive amino acids of SEQ ID NO: 1.

[0012] In some embodiments, the immunogenic peptide comprises 1-5 modified amino acids. In some embodiments, the immunogenic peptide contains a pyroglutamic acid residue at amino acid position 3 and / or 11 of SEQ ID NO: 1.

[0013] In some implementations, the immunogenic peptides are selected from the group consisting of SEQ ID NO: 2-13.

[0014] In some embodiments, the immunogenic carrier protein is selected from the group consisting of: CRM197; diphtheria toxin fragment B (DTFB); DTFB C8; diphtheria toxoid (DT); tetanus toxoid (TT); TT fragment C; pertussis toxoid; cholera toxoid; Escherichia coli (… E. coli LT; Escherichia coli ST; Neisseria meningitidis ( Neisseria meningitidis Outer membrane protein complex (OMPC); from Pseudomonas aeruginosa ( Pseudomonas aeruginosa The exotoxin A of the bacteriophage; mariculture keyhole limpethemocyanin (mcKLH); and the capsid protein of bacteriophage AP205.

[0015] In some embodiments, the immunogenic carrier protein is conjugated at the N-terminus or C-terminus of the immunogenic peptide. In some embodiments, the immunogenic carrier protein is conjugated at the C-terminus of the immunogenic peptide.

[0016] In some embodiments, the immunogenic carrier protein is conjugated to an immunogenic peptide using a linker. In some embodiments, the linker is selected from the group consisting of: N-γ-maleimide butyryloxysuccinimide ester (GMBS); polyethylene glycol (PEG); aminocaproic acid (Ahx); thiol-reactive crosslinking agents; maleimide (MA) linkers; oligopeptides; dendritic polymers; cyclodextrins; and glycine-rich peptides.

[0017] In some embodiments, the pharmaceutical composition further comprises a spacer consisting of 1-10 amino acids adjacent to the linker.

[0018] In some embodiments, the immunogenic peptide comprises SEQ ID NO: 2 and the immunogenic carrier protein is CRM197.

[0019] In some other embodiments, the immunogenic peptide is linked to CRM197 via a GMBS linker, and the composition also includes a glycine-cysteine ​​spacer between the immunogenic peptide and the GMBS linker.

[0020] In some embodiments, the immunogenic peptide is a monomer. In some embodiments, the immunogenic peptide is a polymer.

[0021] In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable adjuvant. In some embodiments, the pharmaceutically acceptable adjuvant is selected from the group consisting of: glucopyranosyl lipid adjuvants (GLA); AVT1; AVT2; AVT3; AVT4; AVT5; AVT6; AVT7; QS-21; aluminum-based adjuvants; saponin-based adjuvants; and TLR7 / 8 agonists.

[0022] In some implementations, pharmaceutically acceptable adjuvants are AVT1, AVT5, or AVT7.

[0023] In another aspect, this disclosure provides a method for preventing or treating a disease associated with Aβ amyloid deposits in the brain of a patient in need of such treatment, comprising administering an effective dose of a pharmaceutical composition comprising an immunogenic peptide of at least six consecutive amino acids of SEQ ID NO: 1 and an immunogenic carrier protein.

[0024] In some embodiments, the immunogenic peptide is missing 1-10 amino acids at the N-terminus or 1-33 amino acids at the C-terminus of SEQ ID NO: 1. In other embodiments, the immunogenic peptide is missing 1-10 amino acids at the N-terminus and 1-33 amino acids at the C-terminus of SEQ ID NO: 1.

[0025] In some embodiments, the immunogenic peptide comprises at least 10 consecutive amino acids of SEQ ID NO: 1.

[0026] In some embodiments, the immunogenic peptide comprises 1-5 modified amino acids. In some embodiments, the immunogenic peptide contains a pyroglutamic acid residue at amino acid position 3 and / or 11 of SEQ ID NO: 1.

[0027] In some implementations, the immunogenic peptides are selected from the group consisting of SEQ ID NO: 2-13.

[0028] In some embodiments, the immunogenic carrier protein is selected from the group consisting of: CRM197; diphtheria toxin B fragment (DTFB); DTFB C8; diphtheria toxoid (DT); tetanus toxoid (TT); TT fragment C; pertussis toxoid; cholera toxoid; Escherichia coli LT; Escherichia coli ST; Neisseria meningitidis outer membrane protein complex (OMPC); exotoxin A from Pseudomonas aeruginosa; marine cultured keyhole leucine (mcKLH); and bacteriophage AP205 coat protein.

[0029] In some embodiments, the immunogenic carrier protein is conjugated at the N-terminus or C-terminus of the immunogenic peptide. In some embodiments, the immunogenic carrier protein is conjugated at the C-terminus of the immunogenic peptide.

[0030] In some embodiments, the immunogenic carrier protein is conjugated to an immunogenic peptide using a linker. In some embodiments, the linker is selected from the group consisting of: N-γ-maleimide butyryloxysuccinimide ester (GMBS); polyethylene glycol (PEG); aminocaproic acid (Ahx); thiol-reactive crosslinking agent; maleimide (MA) linker; oligopeptide; dendritic polymer; cyclodextrin; and glycine-rich peptide.

[0031] In some embodiments, the pharmaceutical composition further comprises a spacer consisting of 1-10 amino acids adjacent to the linker.

[0032] In some embodiments, the immunogenic peptide comprises SEQ ID NO: 2 and the immunogenic carrier protein is CRM197.

[0033] In some other embodiments, the immunogenic peptide is linked to CRM197 via a GMBS linker, and the composition also includes a glycine-cysteine ​​spacer between the immunogenic peptide and the GMBS linker.

[0034] In some embodiments, the immunogenic peptide is a monomer. In some embodiments, the immunogenic peptide is a polymer.

[0035] In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable adjuvant. In some embodiments, the pharmaceutically acceptable adjuvant is selected from the group consisting of: glucopyranosyl lipid adjuvants (GLA); AVT1; AVT2; AVT3; AVT4; AVT5; AVT6; AVT7; QS-21; aluminum-based adjuvants; saponin-based adjuvants; and TLR7 / 8 agonists.

[0036] In some implementations, pharmaceutically acceptable adjuvants are AVT1, AVT5, or AVT7.

[0037] In another aspect, this disclosure provides for the use of the pharmaceutical compositions described in any aspect or embodiment of this disclosure in the preparation of a medicament for the prevention or treatment of diseases associated with Aβ amyloid deposits in the brain of patients in need of it.

[0038] In another aspect, this disclosure provides a method for inducing an immune response against an Aβ peptide in a patient in need, comprising administering to the patient an immunologically effective dose of the pharmaceutical composition described in any aspect or embodiment of this disclosure. In some embodiments, the disease associated with Aβ amyloid deposits in the brain is a disease selected from the group consisting of: Alzheimer's disease (AD); cerebral amyloid angiopathy (CAA); inflammatory CAA; and cerebral amyloid tumor. In some embodiments, the disease associated with Aβ amyloid deposits in the brain is AD. The above overview of the technology is non-limiting, and other features and advantages of the technology will become apparent from the following detailed description and claims. Brief description of the attached diagram The foregoing and other objects, features, and advantages will become apparent from the following description of specific embodiments of the invention as illustrated in the accompanying drawings, wherein the same reference numerals refer to the same parts throughout the different views. The drawings are not necessarily drawn to scale, but rather focus on illustrating the principles of various embodiments of the invention. Figure 1 This demonstrates Aβ conjugated to the CRM197 immunogenic carrier protein via the GMBS linker. pE3_9-G-C The chemical structures of the immunogenic peptides are disclosed in SEQ ID NO: 42 and 2, respectively, in the order of appearance. Figures 2A-1 to 2A-6It displays Aβ pE3-9_G_C Multiple schematic diagrams of the synthesis of tetramers are disclosed in SEQ ID NO: 32 and 43 in the order of appearance. Figures 2B-1 to 2B-7 It displays Aβ pE3-9_G_C Multiple schematic diagrams of the synthesis of the octamer are disclosed, SEQ ID NO: 35. Figure 3A This indicates the total anti-Aβ generated in non-human primates vaccinated with the pE3-9-CRM197 conjugate vaccine. pE3-42 Line graph of antibodies. Figure 3B This indicates the total anti-Aβ generated in non-human primates vaccinated with the pE3-14-CRM197 conjugate vaccine. pE3-42 Line graph of antibodies. Figures 4A to 4D It is shown that Aβ in vaccinated non-human primates 1-42 - and Aβ pE3-42 - A graph of data measuring specific CD4 and CD8 T cell responses. Figure 4A It shows the use of Aβ 1-42 Expression of cytokines in CD4 T cells after peptide stimulation. Figure 4B It shows the use of Aβ pE3-42 Expression of cytokines in CD4 T cells after peptide stimulation. Figure 4C It shows the use of Aβ 1-42 Peptide stimulation of CD8 T cells on cytokine expression. Figure 4D It shows the use of Aβ pE3-42 Expression of cytokines by CD8 T cells after peptide stimulation. The dashed line indicates the positive limit defined by the assay. IL4 = interleukin-4, IL5 = interleukin-5, IFNg = interferon-γ, IL2 = interleukin-2, TNFα = tumor necrosis factor-α. N = 5 individual animals / each vaccine group. Figures 5A to 5D This is shown in the presence of Aβ in vaccinated mice. 1-42 - and Aβ pE3-42 - A graph of data measuring specific CD4 and CD8 T cell responses. Figure 5A It shows the use of Aβ 1-42 Expression of cytokines in CD4 T cells after peptide stimulation. Figure 5B It shows the use of Aβ pE3-42 Expression of cytokines in CD4 T cells after peptide stimulation. Figure 5C It shows the use of Aβ 1-42 Expression of cytokines in CD8T cells after peptide stimulation. Figure 5D It shows the use of aAβ pE3-42Expression of cytokines by CD8 T cells after peptide stimulation. The dashed line indicates the positive limit defined by the assay. IL4 = interleukin-4, IL10 = interleukin-10, IL5 = interleukin-5, IFNg = interferon-γ, IL2 = interleukin-2, TNFα = tumor necrosis factor-α. N = 5 individual mice / vaccine group. Figure 6 This is a bar graph showing the immunoreactivity of human cerebral cortical tissue from Alzheimer's disease patients, stained with serially diluted mouse serum vaccinated with the following peptide vaccines: pE3-9-C, pE3-9-G_C, pE3-10-C, pE3-11-C, pE3-12-C, pE3-13-C, pE3-14-C, pE3-15-C, pE3-15_PEG4_C, pE3-16-C, and pE3-17-C. The area of ​​amyloid plaques (positive immunohistochemical staining) in the vaccinated serum is plotted as a percentage (y-axis) compared to different vaccines, which are shown as serum percentages (x-axis). Dilutions in the range of 1:500 to 1:40,500 are converted to serum percentages (x-axis). Figure 7 This is a bar chart of microglia phagocytosis assay, which shows the phagocytic activity of microglia when serum containing the vaccine is added. It is plotted as the number of Aβ spots phagocytosed by each cell (X-axis) in each treatment group starting with a 2% serum serial dilution (1:2) (Y-axis). Figure 8 This is a graph from a NanoTemper differential scanning fluorescence experiment, demonstrating the intrinsic fluorescence of pE3-CRM conjugates containing various connectors when subjected to elevated temperatures. Figure 9 This is a melting temperature diagram of pE3-CRM conjugates containing various joints. Figure 10 The figure shows a dynamic light scattering experiment, which demonstrates the melting temperature of pE3-CRM197 conjugates containing various junctions. Figure 11 This is a dynamic light scattering diameter analysis diagram of pE3-CRM conjugates containing various joints after applying stirring stress. Figure 12 The graph shows pE3-CRM conjugates with various joint stirring stresses, demonstrating stability as a function of fluorescence. Figure 13 The figure shows an experimental result demonstrating reduced aggregation in pE3-9-CRM samples formulated with polysorbate 80 (PS 80). Figure 14 The graphs and results of the freeze-thaw experiment demonstrate that the sample prepared with 10% sucrose exhibited reduced aggregation. Figures 15A to 15BThis is a graph of microglial phagocytosis assay data used to assess the functional activity of non-human primate (NHP) vaccine serum. The graph shows the phagocytosis of Aβ per cell over time (X-axis) for each treatment group, plotted in hours. pE3-42 Number of spots (Y-axis). Figure 16 This is a graph showing data from microglia phagocytosis assays in HMC3 cells used to assess the functional activity of NHP vaccine serum on day 42. Detailed description As used herein, the articles “a” and “an” refer to one or more (i.e., at least one) grammatical object of that article. For example, “an element” refers to one or more elements. Furthermore, the use of the term “including” and other forms (such as “including,” “included,” and “included”) is not restrictive. The term “about” in the quantitative terminology used in this article refers to the value it modifies plus or minus 10% (rounded to the nearest integer if the value is indivisible, such as the number of molecules or amino acid residues). All ranges disclosed herein include the stated endpoints and can be combined independently (e.g., a range of "from 50 mg to 500 mg" or "50-500 mg" includes the endpoints 50 mg and 500 mg, as well as all intermediate values). The endpoints and any values ​​of the ranges disclosed herein are not limited to precise ranges or values; they are sufficiently imprecise to include values ​​close to these ranges and / or values. As used herein, the term "comprising" can include embodiments of "consisting of" and "substantially consisting of". The terms "comprising", "including", "having", "may", "containing", and variations thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that require the presence of the specified ingredient / step and allow for the presence of other ingredients / steps. However, such a description should be interpreted as also describing the composition or method as "consisting of the listed components" and "substantially consisting of the listed components", which allows for the presence of only the specified component or compound and any acceptable carrier or fluid, and excludes other components or compounds. This disclosure relates to compositions and methods for treating or preventing diseases associated with Aβ amyloid deposition in the brain, such as Alzheimer's disease, in patients who require them. Such methods involve administering Aβ containing an antibody capable of inducing a beneficial immune response against Aβ. 1-42 Pharmaceutical compositions of immunogenic fragments of peptides (i.e., "immunogenic peptides"). Aβ 1-42 The amino acid sequence of the peptide is shown below. Aβ 1-42:DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA (SEQ ID NO:1) In one aspect, this disclosure provides pharmaceutical compositions comprising immunogenic peptides, said immunogenic peptides comprising the consecutive amino acids of SEQ ID NO: 1, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, or 42 consecutive amino acids. In some embodiments, the immunogenic peptide comprises at least six consecutive amino acids of SEQ ID NO: 1. In other embodiments, the immunogenic peptide comprises at least ten consecutive amino acids of SEQ ID NO: 1. In other embodiments, the immunogenic peptide is selected from the group consisting of SEQ ID NO: 2-13. In some embodiments, the immunogenic peptide is SEQ ID NO: 2. Immunogenic peptides In some embodiments, immunogenic peptides include gene products, naturally occurring peptides, synthetic peptides, homologs, orthologs, paralogs, fragments thereof, and other equivalents, variants, and analogs. Peptides can be single molecules (i.e., monomers) or multi-molecular complexes (i.e., polymers), such as dimers, trimers, or tetramers. In some embodiments, the immunogenic peptide is a monomer. In other embodiments, the immunogenic peptide is a polymer. Peptides can also include single-chain or multi-chain peptides and can associate or link together. Most commonly, disulfide bonds are present in multi-chain peptides. The term "peptide" can also be applied to amino acid polymers, wherein at least one amino acid residue is an artificial chemical analog of the corresponding naturally occurring amino acid. A “peptide variant” is a molecule whose amino acid sequence differs from the native or reference sequence. Compared to the native or reference sequence, an amino acid sequence variant may have substitutions, deletions, insertions, or any combination of two or three of the foregoing at certain positions within the amino acid sequence. Typically, the variant shares at least 50% identity with the native or reference sequence. In some embodiments, the variant shares at least 80% or at least 90% identity with the native or reference sequence. "Analog" refers to peptide variants that differ from the parent or initiating peptide by one or more changes in amino acids, such as substitution, addition, or deletion of amino acid residues, while still retaining one or more properties of the parent or initiating peptide. This disclosure provides several types of peptide-based compositions, including variants and derivatives. These include, for example, substitution, insertion, deletion, and covalent variants and derivatives. The term "derivative" is synonymous with the term "variant" and generally refers to a molecule that has been "modified" and / or altered in any way relative to a reference molecule or starting molecule. In some embodiments, the immunogenic peptide comprises 1-5 modified amino acids. In some embodiments, the immunogenic peptide comprises a pyroglutamic acid residue at amino acid position 3 and / or 11 of SEQ ID NO:1. Peptides containing substitutions, insertions and / or additions, deletions, and covalent modifications are included within the scope of this disclosure, relative to reference sequences, particularly the peptide sequences disclosed herein. For example, amino acid residues located at the carboxyl and amino-terminal regions of the amino acid sequence of a peptide or protein may be optionally deleted to provide a truncated sequence. Alternatively, certain amino acids (e.g., C-terminal or N-terminal residues) may be deleted depending on the intended use of the sequence. In some embodiments, the immunogenic peptide lacks 1-10 amino acids at the N-terminus or 1-33 amino acids at the C-terminus of SEQ ID NO: 1. In other embodiments, the immunogenic peptide lacks 1-10 amino acids at the N-terminus and 1-33 amino acids at the C-terminus of SEQ ID NO: 1. When referring to peptides, a “substitution variant” is one in which at least one amino acid residue in the native or starting sequence is removed and a different amino acid is inserted at the same position. Substitution can be single, where only one amino acid in the molecule is substituted, or it can be multiple, where two or more (e.g., 3, 4, or 5) amino acids in the same molecule are substituted. As used herein, the term "conservative amino acid substitution" refers to the substitution of an amino acid normally present in a sequence with a different amino acid of similar size, charge, or polarity. Examples of conservative substitution include the substitution of another nonpolar (hydrophobic) residue, such as isoleucine, valine, and leucine, for another nonpolar residue. Similarly, examples of conservative substitution include the substitution of one polar (hydrophilic) residue for another, such as between arginine and lysine, between glutamine and asparagine, and between glycine and serine. Additionally, the substitution of another basic residue, such as lysine, arginine, or histidine, for another basic residue, or the substitution of one acidic residue, such as aspartic acid or glutamic acid, for another acidic residue, are further examples of conservative substitution. Examples of nonconservative substitution include the substitution of a nonpolar (hydrophobic) amino acid residue, such as isoleucine, valine, leucine, alanine, or methionine, for a polar (hydrophilic) residue, such as cysteine, glutamine, glutamic acid, or lysine, and / or the substitution of a polar residue for a nonpolar residue. As used herein, when referring to peptides, the term "domain" refers to the motif of a peptide having one or more identifiable structural or functional features or properties (e.g., binding capacity, serving as a site for protein-protein interactions). As those skilled in the art will recognize, protein fragments, functional protein domains, and homologous proteins are also considered to be within the scope of the peptide of interest. For example, any protein fragment of a reference protein (meaning a peptide sequence that is at least one amino acid residue shorter than the reference peptide sequence but otherwise identical) is provided herein. In another instance, any protein comprising a stretch of two or more (in specific embodiments, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, or 42) consecutive amino acids that are 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any sequence described herein. In some embodiments, the peptide includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more mutations as shown in any sequence provided herein or mentioned herein. The peptides disclosed herein may share a degree of sequence similarity or identity with reference molecules (e.g., reference peptides), such as molecules described in the art (e.g., engineered or designed molecules or wild-type molecules). The term "identity," as known in the art, refers to the relationship between the sequences of two or more peptides, as determined by sequence comparison. In the art, identity also refers to the degree of sequence relevance between two sequences, as determined by the number of matches between strings of two or more amino acid residues or nucleic acid residues. Identity measures the percentage of identical matches between the smaller of two or more sequences, where gap alignment (if any) is resolved by a specific mathematical model or computer program (e.g., an "algorithm"). The identity of related peptides can be readily calculated by known methods. When applied to peptide sequences, "%identity" is defined as the percentage of residues (amino acid residues or nucleic acid residues) in a candidate amino acid or nucleic acid sequence that are identical to residues in the amino acid or nucleic acid sequence of a second sequence after sequence alignment and, where necessary, introducing gaps to achieve maximum percentage identity. Methods and computer programs used for alignment are well known in the art. Identity depends on the calculation of the percentage of identity, but may differ in value due to gaps and penalties introduced in the calculation. Typically, a variant of a specific peptide has at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with that specific reference peptide, but less than 100%, as determined by sequence alignment procedures and parameters described herein and known to those skilled in the art. Such tools used for alignment include those in the BLAST suite (Stephen F. Altschul, ...). et al. (1997). “Gapped BLAST and PSI-BLAST: a new generation of protein database search programs,” Nucleic Acids Res. 25:3389-3402). Another popular local alignment technique is based on the Smith-Waterman algorithm (Smith, TF & Waterman, MS (1981) "Identification of common molecular subsequences"). J. Mol. Biol.147:195-197). A general global alignment technique based on dynamic programming is the Needleman-Wunsch algorithm (Needleman, SB & Wunsch, CD (1970) "A general method applicable to the search for similarities in the amino acid sequences of two proteins"). J. Mol. Biol. (48:443-453). Recently, a Fast Optimal Global Sequence Alignment Algorithm (FOGSAA) has been developed, which is claimed to produce global alignments of protein sequences faster than other optimal global alignment methods, including the Needleman-Wunsch algorithm. Other tools are described in this paper, particularly in the definition of “identity” below. As used herein, the term "homology" refers to the overall correlation between polymer molecules, such as peptide molecules. Polymer molecules (e.g., peptide molecules) that share a threshold level of similarity or identity determined by the alignment of matching residues are said to be homologous. Homology is a quantitative term describing the relationship between molecules and can be based on quantitative similarity or identity. Similarity or identity is a quantitative term defining the degree of sequence matching between two compared sequences. In some embodiments, polymer molecules are considered "homological" if their sequences are at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical or similar. The term "homology" necessarily refers to a comparison between at least two sequences (peptide sequences). Homology implies that compared sequences evolved in different ways from a common origin. The term "homologous" refers to a first amino acid sequence or nucleic acid sequence (e.g., a gene (DNA or RNA) or protein sequence) that is related to a second amino acid sequence or nucleic acid sequence through inheritance from a common ancestral sequence. The term "homologous" can be applied to relationships between genes and / or proteins that diverged through speciation events, or between genes and / or proteins that diverged through gene replication events. "Orthologous" genes (or proteins) in different species that evolved from a common ancestral gene (or protein) through speciation. Typically, orthologous genes retain the same function during evolution. "Paralleloid" genes (or proteins) are replication-related genes (or proteins) within the genome. Orthologous genes retain the same function during evolution, while paralogous genes evolve new functions, even if these functions are related to the original functions. The term "identity" refers to the overall correlation between polymer molecules, such as peptide molecules. For example, the percentage of identity between two peptide sequences can be calculated by aligning the two sequences for optimal comparison purposes (e.g., gaps can be introduced into one or both of the first and second nucleic acid sequences for optimal alignment, and dissimilar sequences can be ignored for comparison purposes). In some embodiments, the length of the sequences aligned for comparison purposes is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the length of a reference sequence. The percentage of identity between two sequences is a function of the number of common positions shared by the sequences, taking into account the number of gaps that need to be introduced for optimal alignment of the two sequences and the length of each gap. Sequence comparison and determination of the percentage of identity between two sequences can be accomplished using mathematical algorithms. For example, the percentage of identity between two nucleic acid sequences can be determined using methods such as those described in Computational Molecular Biology. , Lesk, AM, ed., Oxford University Press, New York, 1988; Biocomputing: Informatics and Genome Projects, Smith, DW, ed., Academic Press, New York, 1993; Sequence Analysis in Molecular Biology ,von Heinje, G., Academic Press, 1987; Computer Analysis of Sequence Data, Part I, Griffin, AM, and Griffin, HG, eds., Humana Press, New Jersey, 1994; and Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds., M Stockton Press, New York, 1991; each of which is incorporated herein by reference. For example, the percentage of identity between two nucleic acid sequences can be determined using the algorithm of Meyers and Miller (CABIOS, 1989, 4:11-17) (which has been incorporated into the ALIGN program (version 2.0)) using the PAM120 weighted residue table, a gap length penalty of 12, and a gap penalty of 4. Alternatively, the percentage of identity between two nucleic acid sequences can be determined using the GAP program in the GCG package with the NWSgapdna.CMP matrix. Commonly used methods for determining the percentage of identity between sequences include, but are not limited to, those by Carillo, H., and Lipman, D., SIAM. J Applied Math Those described in [Journal Name], 48:1073 (1988); which is incorporated herein by reference. Techniques for determining identity are codified in publicly available computer programs. Exemplary computer software for determining homology between two sequences includes, but is not limited to, the GCG package, Devereux, J. et al. , Nucleic Acids Research ,12, 387 (1984)), BLASTP, BLASTN and FASTA Altschul, SF et al. , J. Molec. Biol. ,215, 403 (1990)). As used herein, when referring to peptides, the term "site" is used synonymously with "residue" and "amino acid side chain" in its reference to amino acid-based embodiments. A site represents a location within a peptide or within a peptide-based molecule that can be modified, manipulated, altered, derivatized, or varied. When referring to peptides, the terms "multiple ends" or "terminus" as used herein refer to the extremes of the peptide. Such extremes are not limited to the first or last site of the peptide and can include additional amino acids in the terminal region. Peptide-based molecules can be characterized as having both an N-terminus (capped by an amino acid with a free amino group (NH2)) and a C-terminus (capped by an amino acid with a free carboxyl group (CH2)). In some cases, proteins are formed from multiple peptide chains (polymers, oligomers) linked together by disulfide bonds or by non-covalent forces. These proteins have multiple N-termini and C-termini. Alternatively, the ends of the peptide can be modified such that, depending on the case, it begins or ends with a non-peptide-based portion such as a carrier protein. Prior to conjugation with a carrier protein, the immunogenic peptide can be chemically activated using any activation or coupling chemistry known in the art to enable the peptide to react with the carrier protein to form a conjugate molecule. As used herein, the term "activated peptide" refers to a peptide that has been chemically modified to enable conjugation with a linker or immunogenic carrier protein. Immunogenic carrier protein The immunogenic peptides disclosed herein can be conjugated to carrier proteins to improve immunogenicity in human subjects. In some embodiments of the invention, CRM197 is used as a carrier protein. CRM197 is a nontoxic variant of diphtheria toxin (DT). The CRM197 carrier protein is a mutant form of DT, which is nontoxic by substitution of a single amino acid at residue 52 in fragment A. In one embodiment, the CRM197 carrier protein is isolated from Corynebacterium diphtheriae grown in a culture medium based on casein amino acids and yeast extract. Corynebacterium diphtheria A culture of strain C7 (P197). In another embodiment, CRM197 is prepared by recombination according to the method described in U.S. Patent No. 5,614,382. Typically, CRM197 is purified by a combination of ultrafiltration, ammonium sulfate precipitation, and ion exchange chromatography. In some embodiments, Pfenex Expression Technology™ (Pfenex Inc., San Diego, CA) is used in the culture of *Pseudomonas fluorescens* (PRM197). Pseudomonas fluorescens CRM197 was prepared in ). Other suitable carrier proteins include other inactivated bacterial toxins, such as DT, diphtheria toxoid fragment B (DTFB), TT (tetanus toxoid) or fragment C of TT, pertussis toxoid, cholera toxoid (e.g., as described in International Patent Application Publication No. WO 2004 / 083251), Escherichia coli LT (heat-labile enterotoxin), Escherichia coli ST (heat-stable enterotoxin), and exotoxin A from Pseudomonas aeruginosa. Bacterial outer membrane proteins such as outer membrane complex c (OMPC), porin, transferrin-binding protein, pneumococcal surface protein A (PspA; see International Patent Application Publication No. WO 02 / 091998), pneumococcal adhesin protein (PsaA), C5a peptidase from group A or group B streptococci, or Haemophilus influenzae protein D, pneumococcal hemolysin (Kuo). et al ., 1995, Infect Immun 63; 2706-13 (including a ply detoxified in some way, such as dPLY-GMBS (see International Patent Application Publication No. WO 04 / 081515) or dPLY-formol), PhtX (including PhtA, PhtB, PhtD, PhtE and Pht protein fusions, such as PhtDE fusions, PhtBE fusions (see International Patent Application Publication Nos. WO 01 / 98334 and WO 03 / 54007)). Other proteins, such as ovalbumin, keyhole lecithin (KLH), bovine serum albumin (BSA) or purified protein derivatives of tuberculin (PPD), PorB (from Neisseria meningitidis ( N. meningitidis ), PD (Haemophilus influenzae protein D; see, for example, European Patent No. EP 0 594610 B), or its immunomodulatory equivalents, synthetic peptides (see European Patent Nos. EP0378881 and EP0427347), heat shock proteins (see International Patent Application Publication Nos. WO 93 / 17712 and WO 94 / 03208), pertussis proteins (see International Patent Application Publication Nos. WO 98 / 58668 and European Patent No. EP0471177), cytokines, lymphokines, growth factors or hormones (see International Patent Application Publication No. WO 91 / 01146), artificial proteins containing multiple individual CD4+ T cell epitopes derived from various pathogens (see Falugi), et al (e.g., 2001, Eur J Immunol 31:3816-3824) For example, the N19 protein (see Baraldoi) et al ., 2004, Infect Immun 72:4884-7), iron uptake protein (see International Patent Application Publication No. WO 01 / 72337), Clostridium difficile ( C. difficileToxins A or B (see International Patent Publication No. WO00 / 61761) and flagellin (see Ben-Yedidia) et al (Immunol Lett 64:9, 1998) can also be used as a carrier protein. Other DT mutants can also be used as carrier proteins, such as CRM176, CRM228, and CRM45 (Uchida). et al. ,1973, J Biol Chem 218:3838-3844); CRM9, CRM45, CRM102, CRM103 and CRM107 and Nicholls and Youle in Nicholls and Youle in Genetically Engineered Toxins, Ed: Frankel, Maecel Dekker Inc, 1992; Glu-148 deletion or mutation to Asp, Gln or Ser and / or Ala 158 deletion or mutation to Gly, and other mutations disclosed in U.S. Patent No. 4,709,017 or U.S. Patent No. 4,950,740; mutations of at least one or more residues Lys 516, Lys 526, Phe 530 and / or Lys 534 and other mutations disclosed in U.S. Patent No. 5,917,017 or U.S. Patent No. 6,455,673; or fragments disclosed in U.S. Patent No. 5,843,711. In some embodiments, the immunogenic carrier protein is selected from the group consisting of: CRM197; diphtheria toxin B fragment (DTFB); DTFB C8; diphtheria toxoid (DT); tetanus toxoid (TT); TT fragment C; pertussis toxoid; cholera toxoid; Escherichia coli LT; Escherichia coli ST; Neisseria meningitidis outer membrane protein complex (OMPC); exotoxin A from Pseudomonas aeruginosa; marine cultured keyhole leucine (mcKLH); and virus-like particles derived from the capsid protein of bacteriophage AP205. In some embodiments, the immunogenic peptide comprises SEQ ID NO: 2, and the immunogenic carrier protein is CRM197. In some embodiments, the immunogenic carrier protein is conjugated at the N-terminus or C-terminus of the immunogenic peptide. In some embodiments, the immunogenic carrier protein is conjugated at the C-terminus of the immunogenic peptide. In some embodiments, the immunogenic carrier protein is conjugated to the immunogenic peptide using a linker. In some embodiments, the linker is selected from the group consisting of: N-γ-maleimide butyryloxysuccinimide ester (GMBS); polyethylene glycol (PEG); aminocaproic acid (Ahx); thiol-reactive crosslinking agents; maleimide (MA) linkers; oligopeptides; dendritic polymers; cyclodextrins; and glycine-rich peptides. In some embodiments, the pharmaceutical composition of this disclosure further comprises a spacer consisting of 1-10 amino acids adjacent to the linker. In some embodiments, the immunogenic peptide is linked to CRM197 via a GMBS linker, and the composition further comprises a glycine-cysteine ​​spacer between the immunogenic peptide and the GMBS linker. Following conjugation, the peptide-conjugated material can be purified using a variety of techniques known to those skilled in the art. These techniques include dialysis, concentration / percolation, tangential flow filtration, ultrafiltration, precipitation / elution, column chromatography (ion exchange chromatography, multimode ion exchange chromatography, DEAE, or hydrophobic interaction chromatography), and depth filtration. See, for example, U.S. Patent No. 6,146,902. In one embodiment, the glycoconjugated material is purified by percolation or ion exchange chromatography or size exclusion chromatography. adjuvant In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable adjuvant. As defined herein, an "adjuvant" is a substance used to enhance the immunogenicity of the immunogenic compositions of the present invention. Immunological adjuvants can enhance immune responses to antigens that are weakly immunogenic when administered alone, such as by not inducing or inducing weak antibody titers or cell-mediated immune responses, increasing antibody titers against antigens, and / or reducing the antigen dose required to effectively achieve an immune response in an individual. Therefore, adjuvants are commonly used to enhance immune responses and are well known to those skilled in the art. Pharmaceutically acceptable adjuvants that enhance the effectiveness of the disclosed immunogenic peptide compositions include, but are not limited to, those described in Example 7 and below. Aluminum salts (alum), such as aluminum hydroxide, aluminum phosphate, and aluminum sulfate, are used as adjuvants. Aluminum salt adjuvants can be either alum-precipitated or alum-adsorbed vaccines. Aluminum salt adjuvants are well-known in the art and described, for example, in Harlow, E. and D. Lane (1988; Antibodies: A Laboratory Manual Cold Spring Harbor Laboratory) and Nicklas, W. (1992; Aluminum salts. Research in Immunology 143:489-493). Aluminum salts include, but are not limited to, hydrated alumina, alumina hydrate, alumina trihydrate (ATH), aluminum hydrate, aluminum trihydrate, and alhydrogel. ® Superfos, Amphogel ® Aluminum hydroxide (III), aluminum hydroxyphosphate (aluminum phosphate adjuvant (APA)), amorphous alumina, aluminum trihydrate, or aluminum trihydroxyphosphate. APA It is an aqueous suspension of aluminum hydroxyphosphate (APA). APA is prepared by precipitating aluminum hydroxyphosphate by blending aluminum chloride and sodium phosphate in a 1:1 volume ratio. After the blending process, the material is reduced in size using a high-shear mixer to achieve a monodisperse particle size distribution. The product is then percolated with physiological saline and steam sterilized. In some implementations, commercially available Al(OH)3 (e.g., Alhydrogel from Denmark / Accurate Chemical and Scientific Co., Westbury, NY) is used. ® (Or Superfos) adsorbs proteins. In another embodiment, protein adsorption depends on the protein's pI (isoelectric pH) and the pH of the culture medium. Proteins with a lower pI adsorb positively charged aluminum ions more strongly than proteins with a higher pI. Aluminum salts can establish a reservoir of antigens that are slowly released over 2-3 weeks, participating in nonspecific activation of macrophages and complement activation, and / or stimulating innate immune responses. See, for example, Lambrecht et al ., 2009, Curr Opin Immunol 21:23. Oil-in-water emulsion formulations(With or without other specific immunostimulants, such as muramyl peptides or bacterial cell wall components), for example (a) MF59 (International Patent Application Publication No. WO 90 / 14837), containing 5% squalene, 0.5% Tween 80 and 0.5% Span 85 (optionally containing varying amounts of MTP-PE), using a microfluidic device, such as MODEL (a) A 110Y microfluidizer (Microfluidics, Newton, MA) formulated into submicron particles; (b) SAF containing 10% squalene, 0.4% Tween 80, 5% Prolynic-block polymer L121 and thr-MDP, either microfluidized into a submicron emulsion or vortexed to generate an emulsion with a larger particle size; (c) a Ribi™ adjuvant system (RAS) (Corixa, Hamilton, MT) containing 2% squalene, 0.2% Tween 80 and one or more bacterial cell wall components derived from the group consisting of: 3-O-deacylated monophosphoryl lipid A-framework (MPL™), trehalose dimethicone ester (TDM), and cell wall skeleton (CWS) as described in U.S. Patent No. 4,912,094, preferably MPL+CWS (Detox™); and (d) Montanide ISA. Muraminopeptides include, but are not limited to, N-acetyl-muramyl-L-threonyl-D-isoglutamine (thr-MDP) and N-acetyl-normurayl-L-alanine-2-(1',2'-dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy)-ethylamine (MTP-PE). In some embodiments, AVT7 is an exemplary oil-in-water emulsion adjuvant containing squalene, Span-85, and PS-20 components stable in an aqueous buffer at pH 5.8. It can be used Saponin adjuvant Examples include Quil A or STIMULON™ QS-21 (Antigenics, Framingham, MA) (see, for example, U.S. Patent No. 5,057,540) or particles derived therefrom, such as ISCOM (an immunostimulatory complex composed of a combination of cholesterol, saponins, phospholipids, and amphiphilic proteins) and Iscomatrix. ® (It has essentially the same structure as ISCOM, but does not contain proteins). Bacterial lipopolysaccharide, synthesizing lipid A analogsFor example, aminoalkyl glucosamine phosphate compounds (AGP), or derivatives or analogs thereof, are available from Corixa and are described in U.S. Patent No. 6,113,918; one such AGP is 2-[(R)-3-tetradecanoyloxytetradecanoylamino]ethyl 2-deoxy-4-O-phosphono-3-O-[(R)-3-tetradecanoyloxytetradecanoyl]-2-[(R)-3-tetradecanoyloxytetradecanoylamino]-bD-glucopyranoside, also known as 529 (formerly known as RC 529), which is formulated in an aqueous form or a stable emulsion. Synthetic polynucleotides For example, oligonucleotides containing the CpG motif (US Patent No. 6,207,646). Stable nanoemulsion or SNE SNE refers to an emulsifier and / or solubilizer and / or surfactant and / or lipid formulation having adjuvant properties in a conjugated vaccine. In an exemplary embodiment, SNE refers to an SNE adjuvant formulation comprising 1) sorbitan trioleate (Span-85); 2) polysorbate-20 (PS-20); 3) squalene and optionally 4) cationic lipids, as described in WO2222169789A1, the entire contents of which are incorporated herein by reference. In some embodiments, the SNE comprises 6 μg / ml to 14 mg / ml of Span-85, 6 μg / ml to 14 mg / ml of PS-20 or PS-80, and 60 μg / ml to 34 mg / ml of squalene. In some embodiments, the SNE also comprises 30 μg / ml to 2.4 mg / ml of cationic lipids. In some embodiments, the cationic lipid is (13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-diene-1-amine. Cytokines Examples include interleukins (such as IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-12, IL-15, IL-18, etc.), interferons (such as gamma interferon), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), tumor necrosis factor (TNF), and co-stimulatory molecules B7-1 and B7-2. Nucleotide sequences containing CpG For example, CpG-containing oligonucleotides, particularly CpG-containing oligodeoxynucleotides (CpGODN). In another embodiment, the adjuvant is ODN 1826, which is available from Coley Pharmaceutical Group. The terms "CpG-containing nucleotide," "CpG-containing oligonucleotide," "CpG oligonucleotide," and similar terms refer to nucleotide molecules of 6-50 nucleotides in length containing an unmethylated CpG moiety. See, for example, Wang... et al ., 2003, Vaccine 21:4297. In another embodiment, any other terminology accepted in the art is contemplated. CpG-containing oligonucleotides include modified oligonucleotides using any synthetic nucleoside internucleotides, modified bases, and / or modified sugars. Methods for using CpG oligonucleotides are well known in the art and described, for example, in Sur et al ., 1999, J Immunol. 162:6284-93; Verthelyi, 2006, Methods Mol Med. 127:139-58; and Yasuda et al ., 2006, Crit RevTher Drug Carrier Syst. 23:89-110. complement For example, the trimer of complement component C3d. Liquid nanoparticles (LNP) adjuvants are a class of adjuvants containing cationic lipids / cholesterol / DSPC / PEG-DMG, as described in WO2015 / 130584A2, the entire contents of which are incorporated herein by reference. Exemplary LNP adjuvants may include cationic lipids / cholesterol / DSPC / PEG-DMG in about the following molar ratios: 59 / 30 / 10 / 1; 58 / 30 / 10 / 2; 43 / 41 / 15 / 1; 42 / 41 / 15 / 2; 40 / 48 / 10 / 2; 39 / 41 / 19 / 1; 38 / 41 / 19 / 2; 34 / 41 / 24 / 1; and 33 / 41 / 24 / 2. In some embodiments, AVT1 is an exemplary LNP adjuvant comprising lipid, cholesterol, DSPC, and PEG-DMG components. In one embodiment, the adjuvant is a mixture of two, three or more of the above adjuvants, such as SBAS2 (which also contains an oil-in-water emulsion of 3-deacylated monophosphoryl lipid A and QS21). Prevention and treatment methods This document provides compositions (e.g., pharmaceutical compositions, including immunogenic peptides, conjugates, and vaccines), methods, kits, and reagents for the prevention, treatment, or diagnosis of neurodegenerative diseases (e.g., Alzheimer's disease) associated with Aβ amyloid deposits in the brain of human patients. In some embodiments, the methods of this disclosure include administering an effective dose of a pharmaceutical composition, such as a vaccine, to a patient in need of it, comprising an immunogenic peptide of at least six consecutive amino acids of SEQ ID NO: 1 and an immunogenic carrier protein. In some embodiments, the immunogenic peptide is missing 1-10 amino acids at the N-terminus or 1-33 amino acids at the C-terminus of SEQ ID NO: 1. In other embodiments, the immunogenic peptide is missing 1-10 amino acids at the N-terminus and 1-33 amino acids at the C-terminus of SEQ ID NO: 1. In some embodiments, the immunogenic peptide comprises at least 10 consecutive amino acids of SEQ ID NO: 1. In some embodiments, the immunogenic peptide comprises 1-5 modified amino acids. In some embodiments, the immunogenic peptide contains a pyroglutamic acid residue at amino acid position 3 and / or 11 of SEQ ID NO: 1. In some implementations, the immunogenic peptides are selected from the group consisting of SEQ ID NO: 2-13. In some embodiments, the immunogenic carrier protein is selected from the group consisting of: CRM197; diphtheria toxin B fragment (DTFB); DTFB C8; diphtheria toxoid (DT); tetanus toxoid (TT); TT fragment C; pertussis toxoid; cholera toxoid; Escherichia coli LT; Escherichia coli ST; Neisseria meningitidis outer membrane protein complex (OMPC); exotoxin A from Pseudomonas aeruginosa; marine cultured keyhole leucine (mcKLH); and bacteriophage AP205 coat protein. In some embodiments, the immunogenic carrier protein is conjugated at the N-terminus or C-terminus of the immunogenic peptide. In some embodiments, the immunogenic carrier protein is conjugated at the C-terminus of the immunogenic peptide. In some embodiments, the immunogenic carrier protein is conjugated to an immunogenic peptide using a linker. In some embodiments, the linker is selected from the group consisting of: N-γ-maleimide butyryloxysuccinimide ester (GMBS); polyethylene glycol (PEG); aminocaproic acid (Ahx); thiol-reactive crosslinking agents; maleimide (MA) linkers; oligopeptides; dendritic polymers; cyclodextrins; and glycine-rich peptides. In some embodiments, the pharmaceutical composition further comprises a spacer consisting of 1-10 amino acids adjacent to the linker. In some embodiments, the immunogenic peptide comprises SEQ ID NO: 2 and the immunogenic carrier protein is CRM197. In some other embodiments, the immunogenic peptide is linked to CRM197 via a GMBS linker, and the composition further includes a glycine-cysteine ​​spacer between the immunogenic peptide and the GMBS linker. In some embodiments, the immunogenic peptide is a monomer. In some embodiments, the immunogenic peptide is a polymer. As used herein, the term "treatment" or "performing treatment" refers to the administration, internally or externally, of a therapeutic component, such as a composition containing any one of the immunogenic peptides, conjugates, or vaccines of the present invention, to a subject or patient having symptoms of one or more diseases or diagnosed with a disease, such as internally or externally, the therapeutic component having therapeutic activity against the disease. In certain embodiments, the immunogenic peptide, conjugate, or vaccine may be administered locally, subcutaneously, intramuscularly, intradermally, intravenously, or systemically. Typically, the component is administered in an effective amount to: (i) alleviate one or more disease symptoms in the treated subject or population, either by inducing the resolution of such symptoms or inhibiting the progression of such symptoms to any clinically measurable extent, or (ii) inhibit or reduce the severity of the disease in an individual. The amount of therapeutic component that effectively alleviates any particular disease symptom and / or inhibits or reduces the severity of the disease (including neurodegenerative diseases in certain embodiments) in an individual may vary based on factors such as, for example, the individual's lesion or disease state, age and / or weight, and the ability of the therapeutic component to elicit a desired response in the individual. Whether one or more disease symptoms have lessened or whether the severity of the disease has been suppressed or reduced can be assessed using any clinical measure commonly used by a physician or other skilled healthcare provider to assess the severity or progression of one or more symptoms or diseases. Treatment with immunogenic peptides, conjugates, or vaccines may also be combined with other interventions (in certain implementations, antibodies, nucleic acids, additional vaccines, and small molecule compounds) to treat other symptoms or diseases. As used herein, the terms “subject, individual” or “patient in need of” refer to a human or animal subject, individual or patient who will be the subject of treatment and who exhibits symptoms of a disease (such as Alzheimer’s disease) associated with the deposition of Aβ amyloid protein in the brain of a patient. vaccine The vaccine disclosed herein can be administered prophylactically or therapeutically to healthy individuals as part of an active immunization program, or early after a diagnosis of a neurodegenerative disease. In some embodiments, the amount of the vaccine of this disclosure provided to cells, tissues, or subjects can be an amount effective for immunoprophylaxis or treatment. Vaccines may be administered in combination with other prophylactic or therapeutic compounds. As a non-limiting example, the prophylactic or therapeutic compound may be an adjuvant or booster. As used herein, when referring to a prophylactic composition such as a vaccine, the term "booster" means the additional administration of the prophylactic (vaccine) composition. A booster (or booster vaccine) may be administered after the early administration of the prophylactic composition. The application time between the initial application of the prophylactic composition and the reinforcing agent can be, but is not limited to, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 1 Days, 36 hours, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 10 days, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 18 months, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 11 years, 12 years, 13 years, 14 years, 15 years, 16 years, 17 years, 18 years, 19 years, 20 years, 25 years, 30 years, 35 years, 40 years, 45 years, 50 years, 55 years, 60 years, 65 years, 70 years, 75 years, 80 years, 85 years, 90 years, 95 years or more than 99 years. In some embodiments, the time between the initial application of the preventive composition and the application of the reinforcing agent may be, but is not limited to, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months or 1 year. In some embodiments, the vaccine may be administered orally, intramuscularly, intradermally, or intranasally, similar to the administration of inactivated vaccines known in the art. In some embodiments, the vaccine is administered intramuscularly. Vaccines can be used in a variety of settings, depending on the prevalence of the underlying disease, family history, or the extent or level of unmet medical needs. As a non-limiting example, vaccines can be used to treat and / or prevent a class of neurodegenerative diseases associated with Aβ amyloid deposits in the brains of patients. Vaccines possess superior properties because they produce significantly higher antibody titers and generate a faster response compared to commercially available non-immunogenic compositions. This article provides pharmaceutical compositions comprising vaccines optionally combined with one or more pharmaceutically acceptable excipients. Vaccines can be formulated or administered alone or in combination with one or more other components. For example, a vaccine (vaccine composition) may contain other components, including but not limited to pharmaceutically acceptable adjuvants. In some embodiments, pharmaceutically acceptable adjuvants are selected from the group consisting of: glucopyranosyl lipid adjuvants (GLA); AVT1; AVT2; AVT3, aVT4; AVT5; AVT6; AVT7; QS-21; aluminum-based adjuvants; saponin-based adjuvants; and TLR7 / 8 agonists. In some implementations, vaccines do not include adjuvants (they do not contain adjuvants). Vaccines may be formulated or administered in combination with one or more pharmaceutically acceptable excipients. In some embodiments, the vaccine composition comprises at least one additional active substance, such as a therapeutic active substance, a prophylactic active substance, or a combination of both. The vaccine composition may be sterile, pyrogen-free, or both sterile and pyrogen-free. General considerations in the formulation and / or preparation of pharmaceutical agents (such as vaccine compositions) can be found, for example, in Remington: The Science and Practice of Pharmacy 21st ed., Lippincott Williams & Wilkins, 2005 (which is incorporated herein by reference in its entirety). In some embodiments, the vaccine is administered to humans, such as human patients or subjects. The formulations of the vaccine compositions described herein can be prepared by any method known or subsequently developed in the field of pharmacology. Typically, such preparation methods involve the following steps: associating an active ingredient (e.g., an immunogenic peptide conjugate) with an excipient and / or one or more other auxiliary ingredients, and then, if necessary and / or desired, dispensing, shaping, and / or packaging the product into desired single- or multi-dose units. The relative amounts of the active ingredient, pharmaceutically acceptable excipients, and / or any other components in the pharmaceutical compositions according to this disclosure will vary depending on the identity, body type, and / or condition of the subject being treated and further depending on the route of administration of the composition. For example, the composition may contain between 0.1% and 100%, such as between 0.5% and 50%, between 1% and 30%, between 5% and 80%, or at least 80% (w / w) of the active ingredient. Vaccine administration patterns Vaccines can be administered via any route that results in a therapeutically effective outcome. These include, but are not limited to, oral, intradermal, intramuscular, intranasal, and / or subcutaneous administration. This disclosure provides methods for administering a vaccine to a subject in need of it. The precise amount required will vary depending on the subject, including species, age and general condition, severity of disease, specific composition, administration method, mode of activity, etc. Vaccine compositions are typically formulated in dose units to facilitate administration and uniform dosage. However, it should be understood that the total daily dose of the vaccine composition may be determined by the attending physician within reasonable medical judgment. The specific therapeutically effective, prophylactically effective, or appropriate imaging dose level for any particular patient will depend on a variety of factors, including the condition being treated and its severity; the activity of the specific compound used; the specific composition used; the patient's age, weight, general health condition, sex, and diet; the timing, route of administration, and excretion rate of the specific compound used; the duration of treatment; drugs used in combination with or concurrently with the specific vaccine used; and similar factors well known in the medical field. In some embodiments, the vaccine composition may be administered at a dosage level sufficient to achieve the desired therapeutic, diagnostic, preventative, or imaging effect (see, for example, the unit dose range described in International Publication No. WO2013078199, the entire contents of which are incorporated herein by reference). The desired dosage may be delivered three times daily, twice daily, once daily, every other day, every three days, every four days, every five days, weekly, every two weeks, every three weeks, every four weeks, every two months, every three months, every four months, every five months, every six months, etc. In some embodiments, the desired dosage may be delivered using multiple administrations (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, or more administrations). When multiple administrations are used, fractionated dosing regimens, such as those described herein, may be used. The vaccine pharmaceutical compositions described herein can be formulated into the dosage forms described herein, such as oral, intranasal, intratracheal, or injectable (e.g., intravenous, intraocular, intravitreal, intramuscular, intradermal, intracardiac, intraperitoneal, intranasal, and subcutaneous) dosage forms. epidemic Seedling preparations and usage methods Some aspects of this disclosure provide vaccine formulations in which the vaccine is formulated in an effective amount to generate an antigen-specific immune response in a subject (e.g., to generate antibodies specific to the Aβ antigenic peptide). "Effective amount" is the dose of vaccine that effectively generates an antigen-specific immune response. Methods for inducing an antigen-specific immune response in a subject are also provided herein. In some implementations, an antigen-specific immune response is characterized by measuring the titer of anti-Aβ antigenic peptide antibodies produced in a subject administered a vaccine such as that provided herein. Antibody titer is a measure of the amount of antibodies in a subject's body, such as antibodies specific to a particular antigen (e.g., an Aβ antigenic peptide) or epitope. Antibody titers are typically expressed as the reciprocal of the maximum dilution that provides a positive result. For example, enzyme-linked immunosorbent assay (ELISA) is a universal assay used to determine antibody titers. In some embodiments, antibody titers are used to assess whether a subject has a neurodegenerative disease or to determine whether immunization is required. In some embodiments, antibody titers are used to determine the strength of an autoimmune response, to determine whether booster immunization is needed, to determine the effectiveness of a prior vaccine, and to identify disease onset or progression. According to this disclosure, antibody titers can be used to determine the strength of the immune response induced by a vaccine in a subject. The above overview of the technology is non-limiting, and other features and advantages of the technology will become apparent from the following detailed description and claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Generally, the nomenclature and laboratory procedures used herein in cell culture, molecular genetics, organic chemistry, and peptide chemistry are those well-known and commonly used in the art. Example The following examples are illustrative and should not be construed as further limitations. All accompanying drawings, references, patents, and published patent applications cited throughout this application are expressly incorporated herein by reference. The abbreviations used in the following embodiments may include, but are not limited to, those shown in Table 1 below. Table 1. Abbreviations Example 1: Synthesis of Aβ peptide To evaluate Aβ pE3 Immunogenicity of peptide antigens, from natural Aβ pE3 Synthetic peptide sequences of varying lengths were prepared. Synthesis spanning Aβp was also performed. E3-9 To Aβ pE3-17 The twelve peptide sequences are shown in Table 2 below. The peptide sequences can also be linked together to form multipeptides as described in Example 2. Each peptide or multipeptide contains a linker and a chemically reactive group at its C-terminus, which enables chemical conjugation to a carrier protein or particle. The linker and chemically reactive group can vary depending on the peptide sequence and the carrier protein or particle used. Unless otherwise stated, Aβ peptide synthesis is performed in three steps. The following protected natural amino acids are used: Fmoc-Arg(Pbf)–OH; Fmoc-Asp(OMpe)-OH, Fmoc-Cys(Trt)–OH; Fmoc-Gln(Trt)–OH; Fmoc-Gly-OH; Fmoc-Glu(OtBu)–OH; Fmoc-His(Trt)–OH; Fmoc-Phe-OH; Fmoc-Ser(t-Bu)–OH; Fmoc-Tyr(t-Bu)–OH; and Fmoc-Val-OH. Step 1: Synthesis. Peptides were synthesized on Rink amide resin (0.25 mmol, 0.35–0.58 mmol / g) using Fmoc / t-Bu chemistry. Amino acids were sequentially incorporated into the resin via single or double coupling cycles. Synthesis was performed manually or automatically as described in Schemes A and B, respectively. For scheme A, Rink amide MBHA resin was placed in a glass sintered vessel equipped with a fused block. The reaction was carried out at room temperature on a fixed-track oscillator. Typical deprotection and coupling reaction conditions are as follows. For deprotection, the reaction mixture was reacted in 20% (v / v) piperidine for 20 minutes. The mixture was filtered and the peptide resin was washed with DMF (5 × 15 mL), DCM (5 × 15 mL), and DMF (5 × 15 mL). For coupling, a pre-activated DMF solution of three equivalents of amino acids, three equivalents of DIC, and three equivalents of HOBt, or a DMF solution of three equivalents of HATU, three equivalents of HOBt, and six equivalents of DIPEA was added to the resin, and the mixture was reacted at room temperature for 3 hours. After the Kaiser assay indicated that the reaction was complete, the mixture was filtered and the peptide resin was washed with DMF (5 × 15 mL), DCM (5 × 15 mL), and DMF (5 × 15 mL). For scheme B, Rink amide MBHA resin was loaded onto a CEM's Liberty Blue microwave-assisted synthesizer (CEM Corp, Matthews, NC, USA). Typical deprotection and coupling reaction conditions were as follows. For deprotection, the reaction mixture was reacted in 0.1 M HOBt with 20% (v / v) piperidine in DMF (at 75°C for 25 s; followed by 90°C for 65 s), followed by 3–4 cycles of DMF washing. For each coupling cycle, four equivalents of amino acids in 5 mL of 0.2 M DMF stock solution were delivered to the resin, followed by four equivalents of DIC in 1 mL of 1 M DMF stock solution and four equivalents of Oxyma in 1 mL of 1 M DMF stock solution. At 90°C, all residues except His were reacted for 2 min, followed by 3–4 cycles of DMF washing. At 50°C, His was reacted for 10 mins, followed by 3–4 cycles of DMF washing. step 2: Pyrolysis. The above peptide-based resins were washed separately with DMF and DCM (3 × 15 mL), then with MeOH (15 mL) and diethyl ether (2 × 15 mL). Finally, the resins were dried under vacuum overnight. Once dried, the resins were treated at room temperature with 10 mL of a reagent mixture (v / v) (95% TFA, 2.5% TIPS, 2.5% DODT) for 3 hours. The lysed mixture was collected by filtration, and the resin was washed with TFA. The combined filtrate containing the peptides was precipitated with sufficient cold (0°C) diethyl ether (approximately 9 × filtrate volume). The precipitated peptides were centrifuged (4000 rpm), and the supernatant was removed. Fresh diethyl ether was added to the peptides, and the mixture was centrifuged again. This process was repeated three times. The precipitated peptides were then dried under high vacuum overnight to obtain a crude product as a white solid. The quality and identity of the desired peptides were confirmed by HPLC and LCMS analysis. The total weight of the crude product obtained was 0.35 g. Step 3: Purification. The crude peptides were dissolved in water and MeCN and purified using a Shimazu Prominence LC-20AP HPLC system equipped with an SPD-M20A diode array detector (Shimadzu Corp., Japan). The HPLC conditions were as follows: Column: Phenomenex Luna C18 5u 100A 250 21.2 mm; Buffer A: 0.01% TFA in H2O; Buffer B: 100% MeCN; Flow rate: 15 mL / min; Gradient: 2-25% over 30 minutes. The HPLC fractions containing the purified peptide product were combined and lyophilized to obtain the final peptide product. Table 2. Pyroglutamic acid-modified Aβ peptides Example 2: Synthesis of multimeric AB peptide The antigen is designed to mimic pathogenic amyloid β plaques to elicit a target-specific immune response. Antigenic Aβ peptides, such as pE3-X, can be further modified into polymers to better capture the structural features of amyloid β plaques, potentially improving the immunogenicity and specificity of the vaccine. These polymer formulations can be achieved through the chemical synthesis of cross-linked Aβ peptide monomers, for example, using linkers such as PEG, oligopeptides, dendritic polymers, cyclodextrins, etc. THPTA (tris(3-hydroxypropyltriazolylmethyl)amine, 18.6 mg, 42.8 μM), copper sulfate (1.37 mg, 8.6 μM), and a stir bar were added to a 5 mL glass vial containing 450 μL of water. The reaction was stirred at room temperature for 2 min, followed by the addition of sodium ascorbate (42.4 mg, 214 μM), and then Ac-SH-alkyne (18.6 mg, 64 μM, prepared as a solution in 250 μL acetonitrile). After stirring for 5 min, azide-bisamine (30 mg, 42.8 μM) was added to the water-acetonitrile reaction mixture. After reacting at room temperature for 1 hour, the formation of the Ac-SH-bisamine product was confirmed by LC-MS, in which all starting materials were consumed. The mixture was purified by column chromatography using a Combi-Flash system (C18 reversed-phase, 0-60% acetonitrile for 10 min, RT = 8 min). The collected product fractions were combined and lyophilized overnight. A colorless oily product was obtained (yield = 10%). Theoretical [M+H]+ = 991.58; Measured [M+H]+ = 991.26. NHS-bis-Mal (2 mg, 2 μM), Ac-SH-diamine (1 mg, 1 μM), and 120 μL of 50 mM sodium phosphate buffer (pH 8) were added to a 0.6 mL microtube. The reaction was incubated overnight at room temperature by rotation. Next, pE3-9 peptide (4 mg, 4 μM) was added to the reaction, and the mixture was incubated at room temperature by rotation for 4 hours. The formation of the desired product was confirmed by LC-MS. The product was purified using a 3K MWCO (molecular weight cutoff) column and centrifugation. The solvent was then removed by lyophilization to obtain the product as a light pink solid. Theoretical [M+4H] 4+ = 1677.75; Actual measurement [M+4H] 4+ = 1677.46. Examples of Aβ monomeric peptides that can conjugate with carrier proteins, as monomers or polymers, are listed in Table 3 below. Specific PE3-9_GC peptides tetrameric using PEG linkers ( Figure 1 ) displayed Figures 2A-1 to 2A-6Prior to conjugation, the peptide (SEQ ID NO: 32) was immediately treated to generate free thiol groups. The peptide (5.3 mg) was dissolved in 100 μL of DMSO and then added to 500 μL of a 1 N hydroxylamine solution (pH 7.4). Immediately after mixing, a deacylated peptide with an m / z of 1668.4 (+4) was detected. The peptide solution was further diluted 5x with conjugation buffer to achieve a hydroxylamine concentration of less than 0.1 N during conjugation. Following the above-described artificial synthesis procedure (Scheme A), the Rink amide MBHA Resin (0.2 mmol, 0.33 mmol / g) was synthesized via SPPS. Figures 2B-1 to 2B-7 Another multimeric peptide (SEQ ID NO: 35) is shown. A K4K2K core was constructed using Fmoc-Lys (Fmoc). Eight Aβ peptide sequences were independently assembled on each chain of the core. The resulting resin was cleaved according to the procedure described above. Crude peptides were purified by HPLC using a linear gradient of buffer B in phase A (A:H2O (0.1% TFA in H2O), mobile phase B:B:CH3CN:PA = 1:2 (0.1% TFA) at a flow rate of 20 mL / min on a YMC-GEL 10 μm C4-HG column (160 mm × 25 mm) (GX-281). The gradient was 24%B-45%B over 40 min. The product eluted at 26 min. The fractions containing the product were combined and lyophilized to give a white solid (34 mg, yield 2.18%) with measured m / z of 1524.3 (+4) and 1089.4 (+6). Table 3. Aβ peptides used for conjugation Example 3: Preparation of Aβ peptide-CRM197 conjugate The purified recombinant CRM197 (diphtheria toxin) was diluted to a total protein concentration of 1 mg / mL with 25 mM HEPES (pH 7.3), 150 mM NaCl, and 5 mM EDTA. CRM197 was activated with the heterobifunctional cross-linking agent N-maleimide butyryloxysuccinimide ester GMBS (TCI America, Portland, OR.USA). A stock solution of 30 mg / mL GMBS was freshly prepared in DMSO (Sigma Aldrich, D2650), and 50 equivalents of GMBS were added to a 1 mg / mL CRM197 solution. The reaction mixture was incubated at ambient temperature for 2 hours. Excess GMBS was removed by gel filtration using a disposable Sephadex® G25 desalting column (Cytiva). The level of maleimide in GMBS-activated CRM197 was measured by consuming N-acetylcysteine ​​with maleimide bound to CRM197, wherein N-acetylcysteine ​​thiols were determined using Ellman's reagent (5,5-dithio-bis-(2-nitrobenzoic acid)). The synthesized Aβ peptide (e.g., the Aβ peptide listed in Table 3 above) was dissolved in 20% DMSO at a concentration of 10 mg / mL. A volume of the peptide solution was added to GMBS-activated CRM197 to achieve a final conjugation reaction with a thiol to maleimide molar ratio of 1.5. The reaction mixture was incubated at 4°C for 16 hours. Unreacted maleimide groups were capped by adding excess N-acetylcysteine. A parallel control of GMBS-activated CRM197 alone was performed using the conjugation protocol. The conjugate was purified by five consecutive centrifugations using 25 mM HEPES at pH 7.3 and 150 mM NaCl in a 30,000 Dalton molecular weight cutoff filter. The purified conjugate was aseptically filtered through a 13 mm 0.2 μm Durapore® PVDF filter unit. Analysis of the Aβ peptide-CRM197 conjugate.The molecular weight of the conjugates was determined by size exclusion chromatography with multi-angle light scattering (MALS), differential refractive index (DRI), and UV detection at 280 nm. 50 μL of the peptide conjugate or control (CRM197 activated with GMBS quenched by N-acetylcysteine) was injected at a flow rate of 0.5 mL / min onto a Superose® 6 Increase 10 / 300GL column (Cytiva, part number GE29-0915-96) equilibrated with PBS + 0.02% sodium azide. The molecular weight of the elution peak was calculated using WyattAstra® software. The peptide loading ratio (moles of peptide / moles of CRM197) was calculated as the difference in molecular weight between the peptide-CRM197 conjugate and the CRM197-only control divided by the molecular weight of the peptide. The peptide loading ratio of the conjugates ranged from 8.5 to 13.9 moles of peptide / moles of CRM197, with an average loading ratio of 11.4 moles of peptide / moles. Alternatively, use Shuler et al. (Shuler, KR, Dunham, RG, and Kanda, P.) J. Immunol. Methods The improved least-squares algorithm described in [156 (1992), 137-149] calculates the molar ratio of peptide to protein by quantitatively comparing the amino acid composition of the conjugate and the control (without peptide). The mass loading of the peptide can be calculated from this ratio using the peptide molecular weight and the molecular weight derived from the amino acid sequence of CRM197 (58.408 Da). Example 4: Preparation of AB peptide-OMPC conjugate Malaysia Imide chemistry.The outer membrane protein complex (OMPC) purified from Neisseria meningitidis was suspended at 5 mg / mL in 50 mM NaHCO3, pH 8.5. Freshly prepared GMBS in 20% DMSO at 30 mg / mL was added to the OMPC to obtain a GMBS to lysine molar ratio of approximately 1.2 (assumed to be 0.42 µmole lysine / mg OMPC Lowry protein [Leanza, WJ, Chupak, LS, Tolman, RL, and Marbug, S. Bioconjug Chem 3 (1992), 514-518]). The reaction was incubated at room temperature for 2 hours. The reaction mixture was desalted by dialysis with a 100,000 Dalton molecular weight cutoff membrane against 25 mM HEPES, pH 7.3, 150 mM NaCl, and 5 mM EDTA. The level of maleimide in GMBS-activated OMPC was measured by consuming N-acetylcysteine ​​via maleimide bound to OMPC, with N-acetylcysteine ​​thiol determined using Ellman's reagent (5,5-dithio-bis-(2-nitrobenzoic acid)). The synthesized Aβ peptide was dissolved in 20% DMSO at a concentration of 10 mg / mL. A certain volume of the peptide solution was added to GMBS-activated OMPC to achieve a final thiol / cis-butenedimide molar ratio of 1.5. The reaction mixture was incubated at 4°C for 16 hours. Unreacted cis-butenedimide groups were capped by adding excess N-acetylcysteine. The conjugate was purified by dialysis with a 100,000 Da molecular weight cutoff dialysis membrane against 25 mM HEPES at pH 7.3 and 150 mM NaCl. Using Shuler et al. (Shuler, KR, Dunham, RG, and Kanda, P.) J. Immunol. Methods The improved least squares algorithm described in [156 (1992), 137-149] calculates the molar ratio of peptide to protein by quantitatively comparing the amino acid composition of the conjugate and the control (without peptide). The peptide loading ratio of the conjugate is 4464 moles of peptide per mole of OMPC. The peptides conjugated to maleimide-activated OMPC are listed in Table 4 below. Table 4. Peptides conjugated with maleimide-activated OMPC Thiol-derived OMPCAlternative chemistry for conjugation involved reacting an Aβ peptide containing a terminal bromoacetyl functional group with thiol-derived OMPC. Purified sterile OMPC was thiolated onto a portion of its surface-accessible lysine residues using the reagent N-acetylhomocysteine ​​thiolactone, NaHT (Sigma Aldrich, St. Louis, MO). OMPC in water was flocculated by centrifugation at approximately 197,000 × g for 60 min at 4 °C, and the supernatant was discarded. An activation buffer (0.11 M sodium borate, pH 11) was added to centrifuge tubes after N2-purge, and the flocculation was dislodged using a glass stir bar. The suspension was transferred to a glass Doens homogenizer and resuspended by 30 agitation cycles. The centrifuge tubes were washed, and the washes were dounced by 30 agitation cycles. The resuspended flocculations and washes were combined in a clean container to obtain an OMPC concentration of approximately 7.8 mg / mL. Solid EDTA and DTT were dissolved in N2-purged activation buffer and added to the reaction at a ratio of 0.106 mg DTT / mg OMPC and 0.57 mg EDTA / mg OMPC. After gentle mixing, NAHT was dissolved in N2-purged water and added to the reaction at a ratio of 0.89 mg NaHT / mg OMPC. The reaction was carried out at ambient temperature in the dark for 3 hours. At completion, OMPC clumped as described above and was resuspended in a Dürns homogenate in N2-purged conjugation buffer (25 mM sodium borate, pH 8.5, 0.15 M NaCl). Aliquots were taken for determination of free thiols by the Ellman assay, and batches were stored in the dark on ice until use. The bromoacetylated peptide was dissolved at 10 mg / mL in N2-purged conjugation buffer and slowly added to the thiolized OMPC solution. The reaction was incubated in the dark at ambient temperature for approximately 16 hours. Residual free OMPC thiols were quenched for 1 hour at ambient temperature with a 5-fold molar excess of N-ethylmaleimide. A thiolized OMPC control was obtained using a parallel conjugation protocol. Upon completion of quenching, the conjugate and control were transferred to a 100,000 Da molecular weight cutoff dialysis unit and thoroughly dialyzed for at least five changes of the conjugation buffer. The finally purified conjugate was stored in sterile polypropylene tubes at 4°C. Analysis of Aβ peptide-OMPC conjugate. Total protein was determined using a modified Lowry assay, and conjugate and control samples were analyzed by quantitative amino acid analysis (AAA). OMPC-specific concentrations were determined from hydrolyzed stable residues not present in the peptide sequence and therefore unique to OMPC proteins. The assay was performed using Shuler et al. (Shuler, KR, Dunham, RG, and Kanda, P.). J. Immunol. Methods The improved least-squares algorithm described in [156 (1992), 137-149] calculates the molar ratio of peptide to protein by quantitatively comparing the amino acid composition of the conjugate and the control (without peptide). The peptide loading ratio of the conjugate is 3963 moles of peptide per mole of OMPC. The mass loading of the peptide can be calculated from this ratio using the peptide molecular weight and the average OMPC mass of 40,000,000 Da. Peptides conjugated with thiol-activated OMPC are listed in Table 5 below. Table 5. Peptides conjugated with thiol-activated OMPC Example 5: Preparation of AB peptide-KLH conjugate A 4 mg / mL suspension of marine-cultured keyhole lepidocrocite was prepared by adding water to Imject polyethylene glycol-modified maleimide-activated mcKLH (ThermoFisher Scientific, Waltham, MA, USA). 0.5 mL of the mcKLH suspension was added directly to 2 mg of pE3_9-GC solid peptide, and the peptide and activated mcKLH were gently mixed and allowed to react overnight at room temperature. The next day, the mixture was centrifuged at 3000 rpm to remove any precipitate formed during the reaction. The supernatant was transferred to a Slide-A-Lyzer 20K MWCO dialysis cartridge (ThermoFisher Scientific, Waltham, MA, USA) for dialysis against PBS buffer. The osmotic residue was collected and sterilized by filtration through a 0.2 μm Millix filter unit (Millipore Corp, Bedford, MA, USA). After 70 hours of acid hydrolysis, the amount of peptide incorporated into the conjugate was estimated by amino acid analysis. The peptide concentration was determined to be 0.17 mg / mL. A negative control was prepared by adding 5 μL of 0.5M N-acetylcysteine ​​solution to 0.5 mL of the activated mcKLH suspension described above. After reacting overnight at room temperature, the mixture was centrifuged at 3000 rpm, and the supernatant was transferred to a 20K MWCO dialysis chamber for dialyzing against PBS buffer. The osmotic residue was collected and sterilized by filtration through a 0.2 u filter unit. Peptides conjugated with maleimide-activated KLH are listed in Table 6 below. Table 6. Peptides conjugated with maleimide-activated KLH Example 6: Preparation of AB peptide-VLP conjugate The Aβ peptide was conjugated to the virus-like particle (VLP) of the AP205 phage capsid protein using the SpyTag / SpyCatcher system. A 1 mg / mL solution of the Aβ peptide containing the SpyTag sequence (SEQ ID NO: 36) was prepared in 25 mM HEPES pH 7.3 and 150 mM NaCl. 0.5 mg of the AP205-SpyCatcher VLP (SEQ ID NO: 37) was added to the peptide at a 1:1 molar ratio and incubated at 4°C for 4 hours. The SpyTag and SpyCatcher sequences are shown in Table 7 below. Table 7. SpyTag and SpyCatcher sequences The conjugates were separated from unreacted peptides using a 30 kDa Amicon rotary filter (Millipore Corp., Bedford, MA, USA) via buffer exchange. The conjugates were sterilized by filtration through a 0.2 μm filter unit (Millipore Corp., Bedford, MA, USA). The amount of peptide incorporated into the conjugates was estimated by shortened-time-of-flight mass spectrometry. Peptide concentrations were determined to be between 20 and 40 μg / mL. The peptides conjugated with VLP are listed in Table 8 below. Table 8. VLP-based conjugates Quality analysis. For reduced mass analysis, a 0.1 mg / mL Aβ peptide-VLP conjugate was prepared in a 25 mM 1,4-dithiothreitol (DTT) solution. The sample was incubated at 50 °C for 10 min. The sample (0.5 μg / sample) was injected into an Agilent 6230 LC-QToF-MS system (capillary voltage: 5 K, desolvation temperature: 400 °C) equipped with an Agilent PLRP-S column (1000A 5 μm, 2.1 × 50 mm). Water containing 0.1% (v / v) formic acid and acetonitrile containing 0.1% (v / v) formic acid were used as mobile phases A and B, respectively. Analysis was performed at 60 °C using the gradients shown in Table 9 below. Table 9. Gradient Conditions for Quality Analysis Example 7: Preparation of adjuvant Aluminum hydroxide. Amorphous aluminum hydroxyphosphate sulfate adjuvant (AAHS) was prepared by precipitating alum with sodium hydroxide. Based on aluminum (Al) 3+The adjuvant concentration was calculated based on the content. The aluminum concentration in each vaccine formulation was 450 μg / ml. In animal studies, the final aluminum dose per injection was 45 μg in a 100 μL volume. Alum + CpG (Type B ODN 1018) Amorphous aluminum hydroxyphosphate sulfate adjuvant (AAHS) was prepared by precipitating alum with sodium hydroxide. Based on aluminum (Al... 3+ Adjuvant concentrations were calculated based on the content of the ingredients. CpG (type B ODN 1018, TriLink) was dissolved in a 20 mM histidine, 100 mM NaCl, pH 6.5 buffer. The stock CpG solution was then filtered through a 0.22 μm PVDF membrane filter (4 mm diameter). AAHS was buffer-exchanged to 20 mM histidine, 100 mM NaCl, pH 6.5 and concentrated by centrifugation. CpG 1018 was added to the AAHS in the formulation buffer and mixed by pipetting. The aluminum concentration in each vaccine formulation was 450 μg / ml. The final aluminum dose per injection in animal studies was 45 μgAl. 3+ Mix 5 μg CpG or 30 μg CpG in a 100 μL volume. Liposomes. Thin-film evaporation was used to prepare a product containing QS-21 (a type of...). Quillaja sciponctria Liposomes containing DOPC (Desert King International, Product 120-2-177), 1,2-dioleoyl-sn-glycero-3-phosphocholine (Avanti™, Product 850375), cholesterol (Avanti™, Product 700100), and GLA were prepared. DOPC, cholesterol, and GLA were dissolved in ethanol. Ethanol was evaporated using RotoVap™ in a round-bottom flask. The lipid membrane was resuspended in 50 mM Na / K phosphate, 100 mM NaCl pH 6.2 buffer after being placed in a water bath at 50°C. The resulting liposomes were extruded through a 0.1 μm polycarbonate filter six times at 50°C. QS-21 and additional 50 mM Na / K phosphate, 100 mM NaCl pH 6.2 buffer were added to the formulation, followed by aseptic filtration through a PES 0.2 μm pore membrane. In some embodiments, AVT5 is an exemplary liposome adjuvant comprising DOPC, cholesterol, GLA, and QS-21 components. AS04-class; TLR4 + Alum.The TLR4 agonist GLA was dissolved in 0.2% triethylamine. The solution was heated, homogenized, and sonicated to achieve complete dissolution and produce uniformly sized particles. The particles were then filtered through a 0.22 μm PES sterile filter. Next, the filtered GLA was added to AAHs in 10 mM histidine, 325 mM NaCl, 0.01% PS80, pH 6.2. The formulation was equilibrated at 2–8 °C for at least 4 hours to ensure complete GLA adsorption to AAHs. A final buffer exchange was performed with 10 mM histidine, 325 mM NaCl, 0.01% PS80, pH 6.2. The supernatant and wash buffer were collected to quantify the amount of unbound GLA (if any). Matrix-M type. Dissolve QS-21 in 150 mM NaCl, 10 mM K / Na Pi pH 6.2. Dissolve DPPC and cholesterol in 20% N-decanoyl-N-methylglucosamine and pipette to mix. Add the dissolved QS-21 to a liposome and mix by pipetting and gentle vortexing. Add 150 mM NaCl, 10 mM K / Na Pi pH 7.4 buffer and mix. Incubate overnight at 30°C with stirring. Dialyze for 24 hours to 150 mM NaCl, 10 mM K / Na Pi pH 7.4, then perform 3x buffer exchange to 150 mM NaCl, 10 mM K / Na Pi pH 6.2 at 24-hour intervals. Filter aseptically through a 0.22 μm pore size PES filter. In animal studies, the final dose per injection was 0.2 μg or 5 μg of GLA in a 100 μL volume. SNE + L608 Squalene, PS-20, Span-85, and L608 ((12Z,15Z)-N,N-dimethyl-2-nonyldocosa-12,15-diene-1-amine) (as described in WO2017070623A1, the contents of which are incorporated herein by reference in their entirety) were combined to generate oil phases at target concentrations of 15, 1.5, 1.5, and 15 mg / mL, respectively. An aqueous buffer (20 mM histidine, pH 5.8) was added to the oil phase and mixed on a stirring plate. A two-step high-pressure homogenization process was employed, followed by aseptic filtration using a PES 0.22 μm pore filter (catalog number 12992). The filtered formulation was diluted with a pH 5.8 buffer of 20 mM histidine, 300 mM NaCl, and 0.2% PS-20 to obtain the final SNE adjuvant formulation targeting 2.4 mg / mL L608. SNE + TLR7 / 8TLR7 / 8 agonist compounds of formula I, Ia, II, IIa, III, IIIa, IV, or IVa, or pharmaceutically acceptable salts thereof, are described in International Patent Application No. PCT / US2024 / 029596, the entire contents of which are incorporated herein by reference. In some embodiments, the TLR7 / 8 agonist compound is N -(5-(4-(4-((5-amino-7-(butylamino)-2 H -pyrazolo[4,3- d Pyrimidin-2-yl)methyl)-3,5-dimethoxyphenyl)pyrazin-1-yl)-5-oxopentyl)stearamide, N -(5-(4-(4-((5-amino-7-(butylamino)-2 H -pyrazolo[4,3- d [Pyrimidin-2-yl)methyl)-3-methoxyphenyl)piperazin-1-yl)-5-oxopentyl)stearamide or N -(4-((4-((5-amino-7-(butylamino)-2 H -pyrazolo[4,3- d Pyrimidin-2-yl)methyl)-3,5-dimethoxybenzyl)methyl)amino)butyl)stearamide. In some exemplary embodiments, the TLR7 / 8 agonist compound is N -(5-(4-(4-((5-amino-7-(butylamino)-2 H -pyrazolo[4,3- d Pyrimidin-2-yl)methyl)-3-methoxyphenyl)piperazin-1-yl)-5-oxopentyl)stearamide. TLR7 / 8 agonist compounds were combined with squalene, PS-20 or PS-80, and Span-85, and diluted with a pH 5.8 buffer of histidine, PS-20, NaCl, L-met, and EDTA to produce SNE adjuvant formulations. LNPLNPs containing L608, DSPC, cholesterol, and PEG-DMG were precipitated via T-mix. Lipids were dissolved in ethanol at a molar ratio of 58 / 10 / 30 / 2 to generate AVT1, an exemplary LNP adjuvant. The lipid / ethanol stream was introduced into an aqueous stream (10 mM citrate buffer, pH 5) using a syringe pump in a t-mix configuration. Two downstream buffer diluents were introduced into the product stream (20 mM sodium citrate, 300 mM NaCl, pH 6.0, and 1X Dulbecco PBS). The resulting LNPs were annealed at room temperature for 30 min, followed by tangential membrane filtration with buffer exchange (20 mM Tris, 10% sucrose, pH 7.5) and concentration. Aliquots were stored at -20°C until the day of animal studies, during which they were thawed at room temperature and diluted to 20 mM Tris, 10% sucrose, pH 7.5. Example 8: In vivo immunogenicity study The immunogenicity of the peptide was tested by preparing a vaccine formulation containing a peptide antigen conjugated to a carrier protein / particle, co-formulated with a vaccine adjuvant. The peptide antigen was conjugated to a carrier protein or particle selected from CRM197, KLH, OMPC, or AP205 virus-like particles (VLPs). The conjugated peptide was co-formulated with the adjuvant described in Example 7. In vivo study protocol in mice.Female C57B16 / NTAC mice (Taconic Biosciences) arrived at the facility and were housed in groups of four on corn cob bedding, with free access to food and water under normal light cycles (lights on at 700 h, off at 1900 h). Mice arrived at 8 weeks of age, and those between 9 and 11 weeks of age were allowed at least one week of acclimatization before the start of the study. On day 0, mice were intramuscularly vaccinated with 0.05 mL of vaccine per quadriceps muscle, for a total infusion volume of 0.1 mL per mouse. The treatment group consisted of eight mice, and the animals were ear-tagged for identification purposes. On day 15, mice were placed in an incubator to promote tail vasodilation and were bled from the tail. Blood was collected in serum separation tubes (SST), centrifuged at 10,000 rpm for 6 minutes, and ~100 μL of serum was transferred to 96-well plates according to the plate plot. On day 28, mice received a second vaccination with the same formulation administered on day 0 (0.05 mL IM per quadriceps muscle, total infusion volume 0.1 mL per mouse). On day 42, mice were euthanized with CO2, CSF was collected, and transferred to 96-well plates according to the plate plot. The thoracic cavity was opened, blood was collected into SST (and processed and plated as described on day 15), the spleen was dissected and placed in a collection vial held on moist ice, and then transcardially perfused to the mice with ice-cold phosphate-buffered saline via syringe. The brain was removed, cut in half, and freshly frozen on dry ice. The tissue was then processed as described in this application. Research protocol in rhesus monkeys. All animal studies were conducted at the New Iberia Primate Research Center (NIRC) (New Iberia, LA) and approved by the Institutional Animal Care and Use Committee (IACUC). These studies used healthy adult Indian rhesus monkeys of either sex. Animals were pre-screened prior to study enrollment and assigned to experimental groups with the aim of minimizing variability based on age, sex, weight, and pre-existing immunity to the vaccine components. Animals were vaccinated according to an established NIRC procedure, which included sedation, shaving of the injection site, and injection of test vaccine material. The vaccine was delivered intramuscularly (IM) into the deltoid muscle, with each group receiving 0.5 ml of vaccine (total volume 1.0 ml per animal). Animals were administered the vaccine on days 0 and 28 post-immunization, and Draize scores at the injection site were monitored to determine reactivity. To assess the immunogenicity of the vaccine test material, venous blood was collected longitudinally at appropriate time points to separate serum, plasma, and peripheral blood mononuclear cells (PBMCs). Serum was separated from whole blood using appropriately sized non-additive serum separator vacuum tubes (SST), allowed to coagulate, centrifuged to harvest the serum, and transferred to long-term storage vials. Plasma was separated from whole blood by collecting it into tubes containing EDTA, centrifuged, and collected for long-term storage. PBMCs were isolated by collecting 30 ml of whole blood into appropriate vacuum tubes containing EDTA, processed by density gradient centrifugation according to NIRC standard operating procedures, and frozen before long-term storage. Example 9: Binding of vaccine-treated animal serum with AB peptide To determine the immunogenicity of the vaccine formulation, mice were immunized twice, four weeks apart. Two weeks after each immunization, blood samples were collected, and serum levels of Aβ were tested by ELISA. pE3-42 and Aβ 1-42 The antibody titers are shown in Table 11 below for Aβ. pE3-42 and Aβ 1-42 The results are PD1 and PD2 after administration. To further evaluate the immunogenicity of the vaccine formulation, non-human primates were immunized twice, four weeks apart. Two weeks after each immunization, blood samples were collected, and serum levels against Aβ were tested by ELISA. pE3-42 and Aβ 1-42 Antibody titer for Aβ. pE3-42 and Aβ 1-42 These titers are shown in Table 12. Using Aß pE3-42 Immunogenicity was assessed by titer and compared with that of Aβ. pE3-42 With Aβ 1-42 To assess the titer for Aß pE3-42 The specificity of the enzyme is as described in Example 3 of International Patent Application Publication WO2010005858A (the entire contents of which are incorporated herein by reference), by means of enzyme-linked immunosorbent assay (ELISA) to detect Aβ peptide and Aβ peptide in mouse or non-human primate (NHP) serum. pE3-42 and Aβ 1-42Evaluation of the binding. Black 384-well immunoassay plates (Thermo Fisher Scientific, Rochester, NY) were filled with 25 μL per well in PBS at a concentration of 0.25 μg / mL Aβ. pE3-42 or Aβ 1-42 The peptides were coated and stored overnight at 4°C. Vaccine-treated animal serum was prepared in milk-PBST, with an initial 1:50 serum dilution followed by 4-fold serial dilutions to achieve 10-point, 4-fold titrations of animal serum in milk-PBST across the serum-blocking plate. Each individual animal serum sample was plated across the serum-blocking plate in this manner. The assay plate was then washed six times with PBS (PBST) containing 0.05% Tween-20 and blocked for 1 hour with 80 μL of 3% skim milk in PBST per well (milk-PBST). Next, the plate was washed once, and 20 μL of serum was flushed from the serum-blocked plate into the assay plate. The assay plate with serum in the wells was incubated in a humidified incubator at 22°C for 2 hours. The assay plate was then washed six times with PBS (PBST) containing 0.05% Tween-20. Next, 20 μL of freshly prepared HRP-conjugated secondary antibody was applied to each well and incubated in a humidified incubator at 22°C for 1 hour. The antibodies used in this ELISA assay are shown in Table 10 below. Table 10. ELISA Antibodies The assay plate was then placed outdoors and incubated at room temperature for 10 min. The plate was washed six times with PBS (PBST) containing 0.05% Tween-20. West Pico Plus chemiluminescent substrate was prepared according to the manufacturer's protocol (ThermoFisher Scientific, Rochester, NY). 20 μL of the freshly prepared chemiluminescent substrate was added to each well of the assay plate and incubated outdoors at room temperature for 15 min. The luminescence was read on an Envision Multimode plate reader (Perkin Elmer, Waltham, MA) set to read ultrasensitive luminescence at 0.1 sec / well. Then, the interpolated ELISA titer was calculated from the raw data of the plate reader using a threshold of 50,000 relative luminous units (RLU) counts. The titer calculation is as follows. Titer = (Initial dilution / Successive dilution factor) x (Successive dilution factor^t) Where t = x - [(cutoff value - L) / (HL)] H = High-hole count = First hole count exceeding the cutoff value L = Low-hole count = First hole count below the cutoff value x = Number of low-hole holes = Column # of "Low-hole count" Cutoff value = 50,000 counts The interpolated titer is calculated at the x-dilution point, where the line intersects at 50,000 RLU between data points above and below the 50,000 RLU threshold. Samples that do not intersect the threshold at dilution are assigned a placeholder titer of "25". The results of this determination are summarized in Tables 11 and 12 below. Figure 3A and Figure 3B The figure shows the individual animal data, the geometric mean of the data points for each vaccine treatment group, and the 95% CI. Table 11. Summary of mouse titers for all vaccine conjugates Table 12. Geometric mean of interpolated ELISA titers in NHP animal groups Analysis of CRM197-conjugated antigens using AVT1 adjuvant (lipid nanoparticle adjuvant containing cationic lipids / cholesterol / DSPC / PEG-DMG in a molar ratio of 40 / 48 / 10 / 2, and prepared as described in WO2015 / 130584A2, the entire contents of which are incorporated herein by reference) showed that it was effective against Aβp. E3-42 Relative to Aβ 1-42 Immunogenicity and specificity can vary depending on the antigen sequence and adaptor. Further analysis of the data in Tables 11 and 12 shows that carrier proteins or particles and adjuvants can also affect immunogenicity and specificity. The pE3-9-CRM197+AVT1 formulation represents the desired immunogenicity and specificity against Aβp. E3-42 Relative to Aβ 1-42 Selective formulations. Example 10: Rhesus monkey PBMC restimulation assay and intracellular cytokine staining Evaluation using Aβ pE3-42 or Aβ 1-42 The T-cell response following stimulation is used to determine whether the vaccine induces a response against Aβ. pE3-42 or Aβ 1-42T-cell response. Cryopreserved rhesus monkey PBMCs were rapidly thawed in a 37°C water bath and washed with R10 medium (RPMI-1640, supplemented with 10% fetal bovine serum (FBS), 10 mM HEPES buffer (pH 7.2-7.5), 2 mM L-glutamine, 1x penicillin-streptomycin, 1 mM sodium pyruvate, and 50 μM 2-mercaptoethanol). Cells were incubated overnight at 37°C with 5% CO2. After overnight recovery, cells were counted and allocated into 96-well round-bottom plates and treated with 2 μg / ml transhuman Aβ. 1-42 Sequence (15mer, overlapping 14 amino acids), human Aβ pE3-42 The plates were cultured with either the 15-mer sequence (14 overlapping amino acids) or the CRM197 protein (15-mer, 11 overlapping amino acids) peptide and CD28 / CD49d mouse anti-human co-stimulatory antibody at 1.25 μg / ml. The plates were incubated at 37°C for 60 minutes. After incubation, freshly diluted brevidin A at a final concentration of 12.5 μg / ml was added, and the plates were incubated for another 5 hours. DMSO was added to the simulated control wells instead of the peptide to determine background cytokine expression levels. Following stimulation, PBMCs were washed with phosphate-buffered saline (PBS) and stained with mouse anti-human CCR7-BV650 (clone G043H7, Biolegend) at 37°C for 10 minutes. Live / Dead-fixing Aqua staining agent (Invitrogen) was added to each well and incubated at room temperature for 15 minutes. Cells were then washed with FACS buffer (PBS containing 1% FBS and 0.01% sodium azide) and stained at room temperature for 30 minutes with a mixture of fluorescently labeled antibodies targeting surface markers. Antibodies targeting surface markers included mouse anti-human CD14-BV711 (clone M5E2, Biolegend), mouse anti-human CD20-BV711 (clone 2H7, Biolegend), mouse anti-human CD3-APC-Cy7 (clone SP34.2, BD Biosciences), mouse anti-human CD4-BV605 (clone L200, BD Biosciences), mouse anti-human CD8-BUV395 (clone RPA-T8, BD Biosciences), and mouse anti-human CD95-PE-Cy5 (clone DX2, BD Biosciences). Antibody mixtures for surface staining were prepared in FACS buffer supplemented with Brilliant Stain Buffer Plus (BD Biosciences). After surface staining incubation, samples were washed with FACS buffer, then fixed and permeabilized at 4°C for 25 min with BD cytofix / cytoperm (BD Biosciences). Cells were washed twice with BD perm / wash buffer (BD Biosciences) and then stained at room temperature for 60 minutes with a mixture of fluorescently labeled antibodies targeting intracellular cytokines. Antibodies targeting intracellular cytokines included rat anti-human IL-2-PE (clone MQ1-17H12, BD Biosciences), mouse anti-human TNF-PE-Cy7 (clone Mab11, BD Biosciences), rat anti-human IL-4-PE-CF594 (clone MP4-25D2, BD Biosciences), rat anti-human IL-5-Vio515 (clone JES1-39D10, Miltenyi Biotec), and mouse anti-human IFNg-R718 (clone B27, BD Biosciences). Antibody mixtures for intracellular cytokine staining were prepared in BD perm / wash buffer supplemented with Brilliant Stain Buffer Plus.After incubation, the samples were washed with BD perm / wash buffer and fixed overnight at 4°C with BD stabilizing fixative (BD Biosciences), followed by sample collection on a flow cytometer. All samples were acquired using FACSDiva (BD Biosciences) software on a Symphony A5 flow cytometer. Data analysis was performed using OMIQ (Dotmatics) and a custom R script using Rstudio (Posit). Data cleaning was performed using the OMIQ implementation from flowAI before compensation, scaling, and gating. 1-42 Aβ pE3-42 The percentage of cells that specifically responded to peptide stimulation was calculated by subtracting the frequency of cells expressing each cytokine from those stimulated by the CRM197 peptide library. Figures 4A-4D The data shown in the figure indicate that no significant T-cell response was observed in cells isolated from any vaccinated animal. Example 11: Mouse spleen cell restimulation assay and intracellular cytokine staining To determine the magnitude of the T-cell response to the test vaccine material, spleens from vaccinated mice were harvested, processed into single-cell suspensions, and used to target Aβ. 1-42 Aβ pE3-42 Restimulation with a peptide library of CRM197. Briefly, spleens and R10 medium were placed in 60 mm tissue culture dishes containing steel wire loops (S-3770, Sigma) and mechanically dissociated using a plunger from a sterile 10 ml syringe (BDBiosciences). The cell suspension was collected in 15 ml Erlenmeyer flasks, centrifuged to clump the cells, and then resuspended in ACK lysis buffer (Gibco) to lyse red blood cells. The reaction was then quenched with R10 medium, and the cells were washed twice with R10 medium. The cell suspension was resuspended in a final volume of 2 ml and filtered through a 70 μm cell filter (Cellart) to obtain the final single-cell spleen cell suspension. Cells were counted and aliquoted into 96-well round-bottom plates and stimulated with 2 μg / ml transmolyzed mouse Aβ. 1-42 Sequence (15-mer, overlapping 14 amino acids), mouse Aβ pE3-42Peptides of either the CRM197 protein (15-mer, overlapping 14 amino acids) or the CRM197 protein (15-mer, overlapping 11 amino acids) were cultured together with co-stimulated antibodies against hamster anti-mouse CD28 (clone 37.51, BD Biosciences) and rat anti-mouse CD49d (clone R1-2, BD Biosciences) at 1.25 μg / ml. Plates were incubated at 37°C for 60 min. After incubation, freshly diluted brevidin A was added to a final concentration of 12.5 μg / ml, and the plates were incubated for another 5 h. DMSO was added to simulated control wells instead of the peptide to determine background cytokine expression levels. Following stimulation, spleen cells were washed with phosphate-buffered saline (PBS) and stained with Live / Dead-fixable Aqua stain (Invitrogen) for 15 minutes at room temperature. Samples were washed with FACS buffer (PBS containing 1% FBS and 0.01% sodium azide) and stained with mouse Fc blocks (BD Biosciences) in FACS buffer for 5 minutes at 4°C. Subsequently, a mixture of fluorescently labeled antibodies targeting surface markers was added, and the samples were incubated at 4°C for 30 minutes. Antibodies targeting surface markers included hamster anti-mouse CD3-APC-Cy7 (clone 145-2C11, BD Biosciences), rat anti-mouse CD4-BUV737 (clone RM4-5, BD Biosciences), and rat anti-mouse CD8a-BUV395 (clone 53-6.7, BD Biosciences). The antibody mixture for surface staining was prepared in FACS buffer supplemented with Brilliant Stain Buffer Plus (BD Biosciences). After surface staining incubation, samples were washed with FACS buffer, then fixed and permeabilized at 4°C with BD cytofix / cytoperm (BD Biosciences) for 25 min. Cells were washed with BD perm / wash buffer (BD Biosciences), then stained at 4°C with mouse Fc blocks (BD Biosciences) in BD perm / wash buffer for 5 min. Subsequently, a mixture of fluorescently labeled antibodies targeting the surface markers was added, and the samples were incubated at 4°C for 35 min. Antibodies targeting intracellular cytokines included rat anti-mouse IFNγ-APC (clone XMG1.2, BD Biosciences), rat anti-mouse IL-2-PE-CF594 (clone JES6-5H4, BD Biosciences), rat anti-mouse TNF-PE-Cy7 (clone MP6-XT22, BD Biosciences), rat anti-mouse IL-4-AF488 (clone 11B11, BD Biosciences), rat anti-mouse IL-5-PE (clone TRFK5, BD Biosciences), and rat anti-mouse IL-10-BV421 (clone JES5-16E3, BD Biosciences). Antibody mixtures for intracellular cytokine staining were prepared in BDperm / wash buffer supplemented with Brilliant Stain Buffer Plus.After incubation, the samples were washed twice with BDperm / wash buffer and fixed overnight at 4°C with BD stabilizer (BD Biosciences). Samples were then collected on a flow cytometer. All samples were acquired using FACSDiva (BD Biosciences) software on a Symphony A5 flow cytometer. Data analysis was performed using OMIQ (Dotmatics) and a custom R script using Rstudio (Posit). Data cleaning was performed using the OMIQ implementation from flowAI before compensation, scaling, and gating. Data was analyzed using data from samples processed with Aβ... 1-42 Aβ pE3-42 The percentage of cells that specifically responded to peptide stimulation was calculated by subtracting the frequency of cells expressing each cytokine from those stimulated by the CRM197 peptide library. Example 12: IHC in AD tissue To demonstrate that the vaccine formulation induces antibodies associated with human Alzheimer's disease (AD), the binding of serum to human AD brain tissue was tested. Immunohistochemistry was used to test the reactivity of serum collected from animals treated with PE3-9-GC-CRM + AVT1 for two weeks with PD2 to human AD tissue. Affinity purification of anti-αHPE3 antibody from NHP serum. For anti-Aβ pE3 The antibody was purified by affinity bonding according to the manufacturer's instructions, using pyroglutamic acid Aβ. 3–42 protein (Aβ) pE3-42 AnaSpec was coupled with superparamagnetic Dynabeads M280 TosylActivated (ThermoFisher Scientific). The prepared Aβ was then coupled at room temperature. pE3-42 - The beads were incubated with NHP serum from the vaccine by rotation for 30 min. The bound antibodies were eluted with 0.2 M glycine at pH 2.7 and immediately neutralized with 1 M Tris-HCl at pH 8.0. Immunohistochemistry (IHC) and image analysis.Cerebral cortical blocks from individuals diagnosed with advanced Alzheimer's disease (AD) and having Braak stage 5 or 6 were purchased from Analytical Biological Services Inc (ABS). These samples were rapidly autopsied within a 4-hour postmortem interval prior to freezing. To obtain frozen sections, brain tissue was mounted on a cryostat (Thermo Cryostar NX70, CT=-18°C, OT=-14°C) and sectioned at a thickness of 10 μm. IHC staining with either vaccine-prescribed mouse serum or a positive control antibody was performed on a LeicaBond Rx automated staining instrument using the Bond PolymerRefine Detection System IHC protocol F (DS9800; Leica Biosystems, UK). Briefly, after treatment with a Background Punisher (BP974M, Biocare Medical) using Protein Block and Peroxide Block, sections were immunostained with primary antibody / vaccinated animal serum diluted in Da Vinci Green Diluent (PD900M, Biocare Medical). Starting with a 500-fold dilution of initial serum or 1 mg / mL antibody, perform 8-point 3X serial dilutions of serum. After washing the primary antibody, administer Post Primary (in Tris-buffered saline / 0.1% ProClin). TMRabbit anti-mouse IgG was detected in 10% (v / v) animal serum in 950. After further rinsing, the sections were treated with a polymer (10% (v / v) animal serum containing anti-rabbit poly-HRP-IgG in Tris-buffered saline / 0.1% ProClin™ 950). The sections were rinsed again and then treated with diaminobenzidine tetrahydrochloride (DAB) and hydrogen peroxide to produce visible reaction products. Hematoxylin was used as a nuclear counterstain at the end of staining. After staining, the slides were dehydrated with fractionated alcohol, mounted with DPX mounting medium (06522; Sigma, USA) and covered with coverslips. The slides were imaged using a digital pathology slide scanner - Zeiss Axioscan Z1 (Zeiss) and the images were analyzed using HALO v3.4 software provided by Indica Labs. Experiments were analyzed batch by batch. A deep learning algorithm was trained to classify the images into amyloid plaques and background regions. For this purpose, representative selections for each category were annotated, and the algorithm (Halo AlDensenet V2) was trained using these annotations. Gray matter was annotated as regions of interest (ROIs) for analysis. Image analysis results were output from HALO as .csv files and analyzed in Pivot Charts / Tables in Excel. The percentage of amyloid plaques was quantified, and statistical analysis was performed using GraphPad Prism 9. Figure 6 As shown, serum from animals immunized with pE3-9-G_C-CRM197 highly reacted with AD plaques in brain tissue. Immunohistochemical (IHC) procedure for NHP serum. Cerebral cortical blocks from individuals diagnosed with advanced AD and having Braak stage 5 or 6 were purchased from PrecisionMed. These samples were rapidly autopsied within a 4-hour postmortem interval prior to freezing. To obtain frozen sections, brain tissue was mounted on a cryostat (Thermo Cryostar NX70, CT=-18℃, OT=-14℃) and sectioned at a thickness of 10 μm. Staining was performed using the modified Bond Polymer Refine Detection System IHC protocol F (DS9800; Leica Biosystems, UK) on a Leica Bond Rx automated staining instrument using anti-Aβ. pE3 IHC staining of the antibody. In short, prior to staining, anti-Aβ antibodies were labeled with digoxigenin using the Human-on-Human HRP-Polymer Kit (BRR4056KG; Biocare Medical) according to the manufacturer's instructions. pE3Antibody. After treatment with Protein Block and Peroxide Block using Background Punisher (BP974M; Biocare Medical), anti-Aβ antibodies were administered using digoxigenin-labeled anti-Aβ antibodies diluted in Da Vinci Green Diluent (PD900M; Biocare Medical). pE3 Immunostaining of slides was performed using antibodies. Serum was serially diluted 8 times (2X) starting with 2 μg / ml antibody. After washing the primary antibody, Post Primary (mouse anti-digoxigenin secondary (BRR4055G; Biocare Medical)) was applied. After further rinsing, Polymer (MACH 2 mouse HRP-polymer (mHRP520G; Biocare Medical)) was used. Slides were rinsed again and then treated with DAB and hydrogen peroxide to produce visible reaction products. Hematoxylin was used as the nuclear counterstain at the end of staining. After staining, slides were dehydrated with fractionated alcohol, mounted with DPX mounting medium (06522; Sigma, USA), and covered with coverslips. Slides were imaged using a digital pathology slide scanner – Zeiss Axioscan Z1 – and image analysis was performed using HALO v3.6 software provided by Indica Labs. Experiments were analyzed batch by batch. A deep learning algorithm was trained to classify images into amyloid plaques and background regions. For this purpose, representative selections for each category were annotated, and the algorithm (Halo AI Densenet V2) was trained using these annotations. Gray matter was annotated as regions of interest (ROIs) for analysis. Image analysis results were output from HALO as .csv files and analyzed in Pivot Charts / Tables in Excel. The percentage of amyloid plaques was quantified, and the results are shown in Table 13 below. Statistical analysis was performed using GraphPad Prism 9. Table 13. Summary of binding spectra of natural plaques Example 13: Microglia phagocytosis The functional activity of vaccine-induced serum antibodies was further evaluated using mouse and human microglia phagocytosis assays. Assay for phagocytosis by mouse microglia.A mouse microglia phagocytosis assay was performed to evaluate the functional activity of the Aβ vaccine candidate. Mouse microglia were obtained from Transnetyx tissue (C57PMWB) on day 2 after birth. Cells were seeded at a density of 10,000 cells per well in PDL-coated 384-well plates (Perkin Elmer, PEMSD-6057500) using a liquid processor in NB MicroPro medium (NBMicroPro500). The medium was replaced every 2–3 days by removing 50% of the growth medium and adding an equal volume of fresh medium. Cells were allowed to proliferate for 4–5 days, and experiments were performed within one week of seeding. β-amyloid (pE3-42) peptide (AnaSpec; AS-29907) was reconstructed using 100 μL of 1% NH4OH (AnaSpec; AS-61322) and diluted to 0.1 mg / mL by adding an additional 900 μL of PBS buffer. The solution was incubated at 37°C for 10–15 mins to ensure complete dissolution, aliquoted, and then stored at -20°C as a 20 μM stock solution. On the day of assay, the 20 μM stock solution was diluted to 0.5 mM Aβ in NB Micropro medium. pE3-42 The vaccine serum and vaccine conjugate were added to a master block plate (Griener, 781270). For each test combination and vaccine serum sample, a 2% (final) concentration was added initially and serially diluted 2-fold to obtain a 10-point curve. The serum and peptide conjugate were incubated at 37°C for 1 hour. Then, the microglia culture medium was replaced with the peptide and vaccine serum conjugate, and the cells were incubated at 37°C for 1 hour. After this, the cells were washed with PBS and fixed with 4% paraformaldehyde (Electron Microscopy Sciences; 1224SK) for 15 minutes. The cells were then washed with PBS and subjected to immunocytochemistry. The plates were blocked for 1 hour with 10% normal goat serum (Sigma; G9023) and 0.3% Triton-x-100 (Sigma; T8787) in PBS. Afterward, the cells were incubated overnight at 4°C with primary antibodies rabbit Iba-1 (Wako; 019-19741; 1:500) and mouse 6E10 antibody (Biolegend; 803003; 1:1000) in 5% NGS in PBS. The next day, the cells were washed three times with PBS for 5 mins each time. Then, at room temperature for 1 hour, secondary antibodies AlexaFluor rabbit 488 (Molecular probes; A32731; 1:1000) and mouse 555 (Molecular probes; A32727; 1:1000) were added to 5% BSA and 0.3% Tx-100 / PBS. Cells were then washed twice with PBS and incubated with Hoesct (AnaSpec; 83218; 1:5000) for 5 mins. Cells were washed a final time with PBS and then imaged on an Operetta CLS High Content plate imager. Multiple fields of view (15–20) per well and n=3 per treatment group were imaged for vaccine serum evaluation. The images were then analyzed using the built-in Operetta module to assess the Aβ phagocytosis of each microglia. pE3-42 The number of spots. Next, this data is output for final statistical analysis using GraphPad Prism software. For example... Figure 7 As shown, the pE3-9_g_c-CRM197 vaccine group exhibited the strongest phagocytic activity even at lower serum dilutions. Assay for induced phagocytosis by human microglia (iMGl). On day 42, a human phagocytosis assay was performed using human microglia derived from human induced pluripotent stem cells (iPSCs) to assess the functional activity of non-human primate sera with different adjuvants. Non-human primate sera are shown in Table 14 below. Table 14. Non-human primate serum According to the supplier's protocol, the human BX-0900-CS-2M iPS cell line (BrainXell) was cultured and induced to differentiate into human microglia (iMGL). The reagents and culture medium formulations used for culturing and differentiating BX-0900-CS-2M are shown in Tables 15 and 16 below. Table 15. Reagent List Table 16. Basal and Differentiation Culture Media The phagocytosis of HF-488-labeled Aβ peptide by human iMGLs was observed over 24 hours using live-cell imaging. On the day of the experiment, half of the culture medium (50 μL) was removed from the multi-well plate and replaced with 2X cell tracer (ThermoFisher, C34552) at a final concentration of 1:4000 and 1 drop / mL NucBlue (ThermoFisher; R37605), and incubated for 1 hour. During this period, 0.5 μM of labeled Aβ pyro E3-42 peptide (AnaSpec; 83960-3) was prepared in microglia complete differentiation medium and incubated at 37°C in a first plate with 2% NHP serum and a second plate with 1 μg / mL purified NHP day 42 serum for 1 hour. The microglia conditioned medium was replaced with 100 μL of Aβ peptide and serum or antibody complex and incubated at 37°C, while live-cell imaging was performed for 24 hours. Culture plates were imaged at 40x magnification on an Operetta CSL high-content imager. Multiple fields of view per well and n=3 per treatment group were imaged for vaccine serum evaluation. Images were analyzed using Harmony software, and the number of Aβ spots phagocytosed by each cell was determined as a measure of the outcome. Data were output and further analyzed on GraphPad Prism software. A significant increase in phagocytosis was noted in the serum on day 42 compared to day 0 serum. Figure 15A Similarly, on day 42, all groups were given purified NHP serum at a concentration of 1 μg / ml, followed by the addition of labeled Aβ. pE3-42 The phagocytic process and imaging over 24 hours ( Figure 15B The data were plotted as a time progression in hours (X-axis), showing the number of Aβ cells phagocytosed per cell for each treatment group. pE3-42 Number of spots (Y-axis). HMC3 human microglia phagocytosis assay. The phagocytic activity assay was performed using the human microglia cell line HMC3 to assess the functional activity of non-human primate serum with different adjuvants on day 42. HMC3 cells were rotated at 280g for 5 min at room temperature (RT), washed, and resuspended in Maxcyte electroporation buffer to 1×10⁻⁶. 8 The final cell density was determined by cells / ml. The resuspended cells were then treated with 2 μL of 1 μg / μL FCGR1A DNA (100 μL aliquots, 2 μg per 100 cells). 6Electroporation was performed on cells (cells per well). Electroporated cells were transferred to warm medium and seeded in 96-well plates at a density of 1:5000 cells / well. The seeded cells were incubated at 37°C, 5% CO2, and high humidity for 24 hours. On the day of the experiment, half of the medium (50 μL) was removed and replaced with 2X erythrocyte tracer and NucBlue (1 drop / mL) at a final concentration of 1:4000, and incubated for 1 hour. During this period, 0.5 μM of labeled Aβ pyro E3-42 peptide was prepared in HMC3 medium and incubated at 37°C with 1 μg / mL purified NHP day 42 serum for 1 hour. The microglial conditioned medium was replaced with 100 μL of Aβ peptide and serum or antibody complex and incubated at 37°C while the cells were imaged in real time for 24 hours. Cells were imaged in real-time against Abeta HF488 using a 20X cell tracer, and the number of phagocytosed spots was examined using Harmony software. Cells were then fixed for 15 mins with 4% PFA paraformaldehyde (Electron Microscopy Sciences; 1224SK). Plates were imaged at 40X magnification on an Operetta CSL high-content imager. Multiple fields of view per well and n=3 per treatment group were imaged for vaccine serum evaluation. Images were analyzed using Harmony software, and the number of phagocytosed spots per cell was measured as a result. Data were output and further analyzed on GraphPad Prism software. Data were plotted as time over hours (X-axis) for the number of Aβ phagocytosed per cell per treatment group. pE3-42 Number of spots (Y-axis). Example 14: Analysis of the antigen-CRM197 adapter Multiple analyses were performed on pE3-9-CRM197 samples containing different linkers to evaluate their physical stability. Samples were prepared in 364-well plates, and their thermal stability was assessed using a Prometheus NanoTemper differential scanning fluorometry (nanoDSF) instrument. In nanoDSF, proteins in solution were exposed to temperature gradients that caused protein unfolding. The intrinsic fluorescence of the proteins, which mainly originated from the aromatic side chains of tyrosine and tryptophan residues, was examined, and the data were displayed on... Figure 8 In addition, the melting temperature of the pE3-9-CRM197 conjugate and the first derivative of the fluorescence signal at 350 nm were determined relative to the melting temperature of each connector type, as shown below. Figure 9 and Figure 10 As shown. In addition, the possibility of aggregation caused by joints was examined in a tumbling stirring stress experiment. For the experiment, samples were diluted to a concentration of 0.18 mg / mL in a buffer solution containing 25 mM HEPES, 150 mM NaCl, and pH 7.4. The diluted samples were then placed on a magnetic tumbling stirring plate set to 60% power. At specific time intervals (0, 4, 6, and 24 hours), aliquots were removed and transferred to 96-well plates for dynamic light scattering analysis, which measured the intensity of scattered light to determine particle size and aggregation state. These data were displayed in… Figure 11 middle. Additionally, stressed samples were plated in black-walled 96-well plates and treated with PROTEOSTAT dye. This dye selectively binds to aggregated proteins and can be used as an indicator of protein aggregation. Fluorescence was measured on a SpectraMax M5 plate reader, with excitation and emission set to 550 nm and 600 nm, respectively. These data were displayed on... Figure 12 middle. Similar assays were used to evaluate the effects of polysorbate 80 and sucrose on formulation stability. For these experiments, samples were diluted to a concentration of 0.18 mg / mL in buffer solutions containing 25 mM HEPES, 150 mM NaCl, and pH 7.4, and at concentrations of 0, 0.01, 0.02, 0.05, 0.1, or 0.2% PS80. These samples were then placed on a magnetically stirred plate set to 60% power. At specific time intervals (0, 4, 6, and 24 hours), aliquots were removed and transferred to 96-well plates for dynamic light scattering analysis, which measured the intensity of scattered light to determine particle size and aggregation state. Stressed samples were also plated in black-walled 96-well plates and treated with PROTEOSTAT dye. This dye selectively binds to aggregated proteins and can be used as an indicator of protein aggregation. Fluorescence was measured on a SpectraMax M5 plate reader, with excitation and emission set to 550 nm and 600 nm, respectively. Results are shown below. Figure 13 These data confirm that pE3-9_G_C-CRM197 formulated with polysorbate 80 inhibits aggregation. A similar assay was used to assess the effect of sucrose on formulation stability. For this experiment, samples were diluted to a concentration of 0.18 mg / mL in a buffer solution containing 25 mM HEPES, 150 mM NaCl, 10% sucrose, and pH 7.4. Samples underwent 0, 1, 2, or 3 freeze-thaw cycles. After each freeze-thaw cycle, samples were plated in 96-well plates dyed with Proteostat. These data were displayed in… Figure 14 middle. The subject matter disclosed herein is not limited to the specific embodiments and examples described herein. In fact, various modifications to this disclosure beyond those described will become apparent to those skilled in the art, based on the foregoing description and drawings. Such modifications are intended to fall within the scope of the appended claims. All references cited herein (e.g., publications, patents, or patent applications) are incorporated herein in their entirety by reference, and for all purposes, to the extent that each individual reference (e.g., publications, patents, or patent applications) is specifically and individually indicated to be incorporated herein in its entirety by reference. Other embodiments are within the scope of the following claims.

Claims

1. A pharmaceutical composition comprising an immunogenic peptide of at least six consecutive amino acids of SEQ ID NO: 1 and an immunogenic carrier protein.

2. The pharmaceutical composition of claim 1, wherein the immunogenic peptide is deficient in 1-10 amino acids at the N-terminus or 1-33 amino acids at the C-terminus of SEQ ID NO:

1.

3. The pharmaceutical composition of claim 1, wherein the immunogenic peptide is deficient in 1-10 amino acids at the N-terminus and 1-33 amino acids at the C-terminus of SEQ ID NO:

1.

4. The pharmaceutical composition of any one of the preceding claims, wherein the immunogenic peptide comprises at least 10 consecutive amino acids of SEQ ID NO:

1.

5. The pharmaceutical composition of any one of the preceding claims, wherein the immunogenic peptide comprises 1-5 modified amino acids.

6. The pharmaceutical composition of claim 5, wherein the immunogenic peptide comprises a pyroglutamic acid residue at amino acid position 3 and / or 11 of SEQ ID NO:

1.

7. The pharmaceutical composition of any one of the preceding claims, wherein the immunogenic peptide is selected from the group consisting of SEQ ID NO: 2-13.

8. The pharmaceutical composition of any one of the preceding claims, wherein the immunogenic carrier protein is selected from the group consisting of: CRM197; diphtheria toxin B fragment (DTFB); DTFB C8; diphtheria toxoid (DT); tetanus toxoid (TT); TT fragment C; pertussis toxoid; cholera toxoid; Escherichia coli LT; Escherichia coli ST; Neisseria meningitidis outer membrane protein complex (OMPC); exotoxin A from Pseudomonas aeruginosa; marine cultured keyhole leucine (mcKLH); and bacteriophage AP205 coat protein.

9. The pharmaceutical composition of any one of the preceding claims, wherein the immunogenic carrier protein is conjugated at the N-terminus or C-terminus of the immunogenic peptide.

10. The pharmaceutical composition of claim 9, wherein the immunogenic carrier protein is conjugated at the C-terminus of the immunogenic peptide.

11. The pharmaceutical composition of any one of the preceding claims, wherein the immunogenic carrier protein is conjugated to the immunogenic peptide with a linker.

12. The pharmaceutical composition of claim 11, wherein the linker is selected from the group consisting of: N-γ-maleimide butyryl-oxysuccinimide ester (GMBS); polyethylene glycol (PEG); aminocaproic acid (Ahx); thiol-reactive crosslinking agent; maleimide (MA) linker; oligopeptide; dendritic polymer; cyclodextrin; and glycine-rich peptide.

13. The pharmaceutical composition of claim 12, further comprising a spacer comprising 1-10 amino acids adjacent to the linker.

14. The pharmaceutical composition of any one of the preceding claims, wherein the immunogenic peptide comprises SEQ ID NO: 2 and the immunogenic carrier protein is CRM197.

15. The pharmaceutical composition of claim 14, wherein the immunogenic peptide is linked to CRM197 via a GMBS linker, and wherein the composition further comprises a glycine-cysteine ​​spacer between the immunogenic peptide and the GMBS linker.

16. The pharmaceutical composition of any one of the preceding claims, wherein the immunogenic peptide is a monomer.

17. The pharmaceutical composition of any one of the preceding claims, wherein the immunogenic peptide is a polymer.

18. The pharmaceutical composition of any one of the preceding claims further comprises a pharmaceutically acceptable adjuvant.

19. The pharmaceutical composition of claim 18, wherein the pharmaceutically acceptable adjuvant is selected from the group consisting of: glucopyranosyl lipid adjuvants (GLA); AVT1; AVT2; AVT3; AVT4; AVT5; AVT6; AVT7; QS-21; aluminum-based adjuvants; saponin-based adjuvants; and TLR7 / 8 agonists.

20. The pharmaceutical composition of claim 19, wherein the pharmaceutically acceptable adjuvant is AVT1, AVT5, or AVT7.

21. A method for preventing or treating a disease associated with Aβ amyloid deposits in the brain of a patient in need of such treatment, comprising administering an effective dose of a pharmaceutical composition comprising an immunogenic peptide of at least six consecutive amino acids of SEQ ID NO: 1 and an immunogenic carrier protein.

22. The method of claim 21, wherein the immunogenic peptide lacks 1-10 amino acids at the N-terminus or 1-33 amino acids at the C-terminus of SEQ ID NO:

1.

23. The method of claim 21, wherein the immunogenic peptide is deficient in 1-10 amino acids at the N-terminus and 1-33 amino acids at the C-terminus of SEQ ID NO:

1.

24. The method of any one of claims 21-23, wherein the immunogenic peptide comprises at least 10 consecutive amino acids of SEQ ID NO:

1.

25. The method of any one of claims 21-24, wherein the immunogenic peptide comprises 1-5 modified amino acids.

26. The method of claim 25, wherein the immunogenic peptide comprises a pyroglutamic acid residue at amino acid position 3 and / or 11 of SEQ ID NO:

1.

27. The method of any one of claims 21-26, wherein the immunogenic peptide is selected from the group consisting of SEQ ID NO: 2-13.

28. The method of any one of claims 21-27, wherein the immunogenic carrier protein is selected from the group consisting of: CRM197; diphtheria toxin B fragment (DTFB); DTFB C8; diphtheria toxoid (DT); tetanus toxoid (TT); fragment C of TT; pertussis toxoid; cholera toxoid; Escherichia coli LT; Escherichia coli ST; Neisseria meningitidis outer membrane protein complex (OMPC); exotoxin A from Pseudomonas aeruginosa; marine cultured keyhole leucine (mcKLH); and bacteriophage AP205 coat protein.

29. The method of any one of claims 21-28, wherein the immunogenic carrier protein is conjugated at the N-terminus or C-terminus of the immunogenic peptide.

30. The method of claim 29, wherein the immunogenic carrier protein is conjugated at the C-terminus of the immunogenic peptide.

31. The method of any one of claims 21-29, wherein the immunogenic carrier protein is conjugated to the immunogenic peptide using a linker.

32. The method of claim 31, wherein the connector is selected from the group consisting of: N-γ-maleimide butyryl-oxysuccinimide ester (GMBS); polyethylene glycol (PEG); aminocaproic acid (Ahx); thiol-reactive crosslinking agent; maleimide (MA) connector; oligopeptide; dendritic polymer; cyclodextrin; and glycine-rich peptide.

33. The method of claim 32, further comprising a spacer comprising 1-10 amino acids adjacent to the linker.

34. The method of any one of claims 21-33, wherein the immunogenic peptide comprises SEQ ID NO: 2 and the immunogenic carrier protein is CRM197.

35. The method of claim 34, wherein the immunogenic peptide is linked to CRM197 via a GMBS linker, and wherein the composition further comprises a glycine-cysteine ​​spacer between the immunogenic peptide and the GMBS linker.

36. The pharmaceutical composition of any one of claims 21-35, wherein the immunogenic peptide is a monomer.

37. The pharmaceutical composition of any one of claims 21-35, wherein the immunogenic peptide is a polymer.

38. The method of any one of claims 21-37, further comprising a pharmaceutically acceptable adjuvant.

39. The method of claim 38, wherein the pharmaceutically acceptable adjuvant is selected from the group consisting of: glucopyranosyl lipid adjuvants (GLA); AVT1; AVT2; AVT3; AVT4; AVT5; AVT6; AVT7; QS-21; aluminum-based adjuvants; saponin-based adjuvants; and TLR7 / 8 agonists.

40. The method of claim 39, wherein the pharmaceutically acceptable adjuvant is AVT1, AVT5, or AVT7.

41. The method of any one of claims 21-40, wherein the disease associated with amyloid deposits of Aβ in the brain is selected from the group consisting of: Alzheimer's disease (AD); cerebral amyloid angiopathy (CAA); inflammatory CAA; and cerebral amyloid tumor.

42. The method of claim 41, wherein the disease associated with amyloid deposits of Aβ in the brain is AD.

43. Use of the pharmaceutical composition of any one of claims 1-20 in the preparation of a medicament for the prevention or treatment of diseases associated with Aβ amyloid deposits in the brain of patients in need of it.

44. The use as claimed in claim 43, wherein the diseases associated with amyloid deposits of Aβ in the brain are selected from the group consisting of: Alzheimer's disease (AD); cerebral amyloid angiopathy (CAA); inflammatory CAA; and cerebral amyloid tumor.

45. The use as claimed in claim 44, wherein the disease associated with amyloid deposits of Aβ in the brain is AD.

46. ​​A method for inducing an immune response to an Aβ peptide in a patient in need of it, comprising administering to the patient an immunologically effective dose of the pharmaceutical composition according to any one of claims 1-20.

47. The method of claim 46, wherein the disease associated with amyloid deposits of Aβ in the brain is selected from the group consisting of: AD; CAA; inflammatory CAA; and brain amyloidoma.

48. The method of claim 47, wherein the disease associated with amyloid deposits of Aβ in the brain is AD.

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