Peptide immunogen compositions and uses thereof

Abstract

Described herein are improved peptide immunogen compositions comprising a peptide immunogen, and no adjuvant or an effective amount of an aluminum salt adjuvant, wherein the peptide immunogen comprises a target antigenic site linked to a Th epitope. Also described herein are uses of such peptide immunogen compositions for eliciting an immune response to the target antigen. In some embodiments, the immune response is IgGl-based and / or does not involve IgM or innate immunity.

Description

[0001]Attorney Docket No. VXH-00225 ^ PEPTIDE IMMUNOGEN COMPOSITIONS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 611,633, filed December 18, 2023, which is incorporated by reference herein in its entirety. FIELD The present invention relates to compositions comprising a peptide immunogen and no adjuvant or an effective amount of an aluminum salt adjuvant, and uses of such compositions for eliciting an immune response to a target antigenic site, wherein the immune response is IgG1-based and / or does not induce substantial IgM or innate immunity. BACKGROUND Recently peptide immunogen vaccines have been disclosed and tested in the treatment of, e.g., neurodegenerative diseases. Such vaccines are based on artificial peptide immunogens comprising a target epitope (e.g., a B cell epitope) and a T helper (Th) cell epitope. Induction of a specific and effective immune response to a target epitope (e.g., a B cell epitope) requires composition design that focuses the immune response on production of antibodies against the target epitope, and avoids non-specific and / or inflammatory immune responses. Thus, there is a need to develop peptide immunogen compositions that can effectively enhance desired immunogenicity with reduced inflammation and / or non-specific immunogenicity. In particular, there is a long-standing need to develop peptide immunogen compositions that induce effective and specific immune response to self-antigens associated with chronic or neurodegenerative diseases, e.g., those that require administration of such compositions to a patient over a long period of time. There is a long-standing need in the art to improve peptide immunogen compositions such that specific immune response to target antigens can be induced without also inducing severe undesired side effects (e.g., non-specific and / or inflammatory immune responses). ^ ^ Attorney Docket No. VXH-00225 ^ SUMMARY OF THE INVENTION In some aspects, the present disclosure provides a peptide immunogen composition comprising a peptide immunogen comprising a heterologous Th epitope linked to a target antigenic site (e.g., a B cell epitope or an immunologically reactive analogue thereof), wherein the target antigenic site (e.g., B cell epitope or an immunologically reactive analogue thereof) ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ wherein the peptide immunogen composition does not comprise an adjuvant or comprises a compatible adjuvant in an amount of up to about 1.6 mg / mL, wherein the compatible adjuvant is aluminum-based (such as one or more aluminum salts). In some embodiments, the peptide immunogen composition further comprises a polyanionic CpG oligonucleotide but does not comprise an adjuvant other than the compatible adjuvant. In some embodiments, the one or more aluminum salts is aluminum phosphate and / or aluminum hydroxide. In some embodiments, the one or more aluminum salts is aluminum phosphate. In some embodiments, the one or more aluminum salts is aluminum hydroxide. In some embodiments, the compatible adjuvant is in an amount of about 0.8 mg / mL to about 1.6 mg / mL. In some embodiments, the compatible adjuvant is in an amount of about 1.6 mg / mL. In some embodiments, the compatible adjuvant is in an amount of about, less than, or no more than 0.8 mg / mL. In other embodiments, the peptide immunogen composition does not comprise any adjuvant, i.e., does not comprise a compatible adjuvant. In some embodiments, the peptide immunogen composition comprises a polyanionic CpG oligonucleotide. In some embodiments, the polyanionic CpG oligonucleotide is CpG1, CpG2 or CpG3 (e.g., CpG1). In some embodiments, CpG1 comprises the amino acid sequence 5’ TCgTCgTTTTgTCgTTTTgTCgTTTTgTCgTT 3’ of SEQ ID NO: 81 (e.g., which is fully phosphorothioated). In some embodiments, the polyanionic CpG oligonucleotide is present in an amount up to about 200 µg / mL. In some embodiments, the polyanionic CpG oligonucleotide is present in an amount of about 100 µg / mL to about 200 µg / mL. In some embodiments, the polyanionic CpG oligonucleotide is present in an amount of about 200 µg / mL. In some embodiments, the polyanionic CpG oligonucleotide is present in an amount of about 100 µg / mL. In some embodiments, the heterologous Th epitope is an artificial Th epitope. In some embodiments, the heterologous Th epitope is a promiscuous Th epitope. In some embodiments, the heterologous Th epitope is an artificial and promiscuous Th epitope. In some embodiments, the heterologous Th epitope comprises or has an amino acid sequence according to the formula ISIXEIXXVIVIVXXIEXILF (SEQ ID NO: 132), wherein X is any ^ ^ Attorney Docket No. VXH-00225 ^ amino acid. In some embodiments, the heterologous Th epitope comprises or has the amino acid sequence ISITEIKGVIVHRIETILF (SEQ ID NO: 32) or ISISEIKGVIVHKIETILF (SEQ ID NO: 30). In some embodiments, the heterologous Th epitope has the amino acid sequence ISITEIKGVIVHRIETILF (SEQ ID NO: 32). In some embodiments, the target antigenic site (e.g., B cell epitope) does not comprise any Th epitope. In some embodiments, the peptide immunogen does not comprise an endogenous Th epitope. In some embodiments, the peptide immunogen does not comprise a naturally occurring Th epitope. In some embodiments, the peptide immunogen does not comprise a Th epitope naturally occurring in a pathogen protein (e.g., wherein the pathogen protein is Measles Virus Fusion (MVF) protein, Hepatitis B Surface Antigen (HBsAg), influenza protein, Clostridium tetani protein, Bordetella protein, Diphtheria protein, Plamsodium falciparum protein, Schistosoma mansoni protein, MCMV protein, or Epstein- Barr virus (EBV) protein). In some embodiments, the target antigenic site (e.g., B cell epitope) is a peptide from a protein associated with or involved in pathogenesis of a disease or condition. In some embodiments, the disease or condition is a chronic disease or condition. In some embodiments, the disease or condition is a neurodegenerative or allergic disease or condition. In some embodiments, the disease or condition is an inflammatory disease or condition (e.g., chronic inflammation). In some embodiments, the disease or condition is an autoimmune disease or condition. In some embodiments, the disease or condition is cancer. In some embodiments, the neurodegenerative, chronic or allergic disease or condition is tauopathy, Alzheimer’s, synucleinopathy, Parkinson’s, dementia with Lewy bodies (DLB), multiple system atrophy (MSA), migraine, hypercholesterolemia, hyperlipidemia, or atopic dermatitis. In some embodiments, the target antigenic site (e.g., B cell epitope) is 7 to 50 amino acids in length, 7 to 25 amino acids in length, 7 to 20 amino acids in length, or 7 to 15 amino acids in length. In some embodiments, the target antigenic site (e.g., B cell epitope) is a peptide from alpha-synuclein protein, Tau protein, ^ amyloid protein, calcitonin gene-related peptide (CGRP), proprotein convertase subtilisin / kexin type 9 (PCSK9), interleukin-31, or membrane-bound IgE. In some embodiments, the B cell epitope is or comprises the amino acid sequence of EMPSEEGYQD of SEQ ID NO: 8 (which is from alpha-synuclein). In some embodiments, the B cell epitope is or comprises the amino acid sequence of VPTNVGSKAF of SEQ ID NO: 51 (which is from CGRP). In some embodiments, the B cell epitope is or comprises the amino acid sequence of SIPWNLERIT of SEQ ID NO: 55 (which is from PCSK9). In some embodiments, the B cell epitope is or comprises the amino acid ^ ^ Attorney Docket No. VXH-00225 ^ sequence of DAEFRHDSGYEVHH of SEQ ID NO: 1 (which is from amyloid ^ protein). In some embodiments, the B cell epitope is or comprises the amino acid sequence of IKHVPGGGSVQIVYK of SEQ ID NO: 13 (which is from Tau protein). In some embodiments, the B cell epitope is or comprises the amino acid sequence of DHAGTYGLGD of SEQ ID NO: 15 (which is from Tau protein). In some embodiments, the B cell epitope is or comprises the amino acid sequence of AILSSTNVGSNTY of SEQ ID NO: 50 (which is from IAPP). Immunologically reactive analogues of such B cell epitopes are also contemplated herein. In some embodiments, the target antigenic site (e.g., B cell epitope) is not or does not comprise the amino acid sequence EMPSEEGYQD (SEQ ID NO: 8). In some embodiments, the target antigenic site (e.g., B cell epitope) is not or does not comprise the amino acid sequence VPTNVGSKAF (SEQ ID NO: 51). In some embodiments, the target antigenic site (e.g., B cell epitope) is not or does not comprise the amino acid sequence SIPWNLERIT (SEQ ID NO: 55). In some embodiments, the target antigenic site (e.g., B cell epitope) is not or does not comprise the amino acid sequence DAEFRHDSGYEVHH (SEQ ID NO: 1). In some embodiments, the target antigenic site (e.g., B cell epitope) is not or does not comprise the amino acid sequence IKHVPGGGSVQIVYK (SEQ ID NO: 13). In some embodiments, the target antigenic site (e.g., B cell epitope) is not or does not comprise the amino acid sequence DHAGTYGLGD (SEQ ID NO: 15). In some embodiments, the target antigenic site (e.g., B cell epitope) is not or does not comprise the amino acid sequence AILSSTNVGSNTY (SEQ ID NO: 50). In some embodiments, the heterologous Th epitope is covalently linked to a B cell epitope with a heterologous linker comprising one or more naturally occurring amino acids and / or non-naturally occurring amino acids. In some embodiments, the heterologous linker comprises one or more lysine (e.g., a polylysine linker). In some embodiments, the heterologous linker comprises epsilon lysine (^K). In some embodiments, the heterologous linker comprises three or four lysines. In some embodiments, the linker is ^K-KKK (SEQ ID NO: 130) or KKK-^k (SEQ ID NO: 129). In some embodiments, the peptide immunogen is amidated (comprises an amide group), e.g., at the C-terminal end. In some embodiments, the peptide immunogen is not amidated (does not comprise an amide group), e.g., at the C-terminal end. In some embodiments, the peptide immunogen comprises one of the following formulae: (Th)m-(A)n-(B)-X ^ ^ Attorney Docket No. VXH-00225 ^ (B)-(A)n-(Th)m-X, wherein: Th is the heterologous ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ A is an amino acid ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ B is the B cell epitope, optionally wherein the B cell epitope ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ X is an -COOH or - CONH2of an amino acid. In particular, X is -CONH2when the peptide immunogen has an amide group or is amidated. In some embodiments, n is 1 to 4. In some embodiments, n is 1. In some embodiments, m is 1. In some embodiments, the peptide immunogen does not comprise any other epitope, peptide or protein sequence. In some embodiments, the peptide immunogen is or comprises the amino acid sequence ISITEIKGVIVHRIETILF-^K-KKK-EMPSEEGYQD (SEQ ID NO: 92). In some embodiments, the peptide immunogen is or comprises the amino acid sequence ISITEIKGVIVHRIETILF-^K-KKK-VPTNVGSKAF (SEQ ID NO: 107). In some embodiments, the peptide immunogen is or comprises the amino acid sequence SIPWNLERIT-KKK-^K-ISITEIKGVIVHRIETILF (SEQ ID NO: 113). In some embodiments, the peptide immunogen is or comprises the amino acid sequence DAEFRHDSGYEVHH-^K-KKK-ISITEIKGVIVHRIETILF (SEQ ID NO: 88). In some embodiments, the peptide immunogen is or comprises the amino acid sequence DAEFRHDSGYEVHH-^K-KKKIITITRIITIITTID (SEQ ID NO: 89). In some embodiments, the peptide immunogen is or comprises the amino acid sequence ISITEIKGVIVHRIETILF- ^K-KKK-IKHVPGGGSVQIVYK (SEQ ID NO: 98). In some embodiments, the peptide immunogen is or comprises the amino acid sequence DHAGTYGLGD-KKK-^K- ISITEIKGVIVHRIETILF (SEQ ID NO: 100). In some embodiments, the peptide immunogen composition comprises the peptide immunogen of amino acid sequence DAEFRHDSGYEVHH-^K-KKK-ISITEIKGVIVHRIETILF (SEQ ID NO: 88) and the peptide immunogen of amino acid sequence DAEFRHDSGYEVHH-^K- KKKIITITRIITIITTID (SEQ ID NO: 89). In some embodiments, the peptide immunogen is not or does not comprise (or the composition does not comprise) the amino acid sequence ISITEIKGVIVHRIETILF-^k-kkk- EMPSEEGYQD (SEQ ID NO: 92). In some embodiments, the peptide immunogen is not or does not comprise (or the composition does not comprise) the amino acid sequence ISITEIKGVIVHRIETILF-^k-kkk-VPTNVGSKAF (SEQ ID NO: 107). In some embodiments, the peptide immunogen is not or does not comprise (or the composition does not comprise) the amino acid sequence SIPWNLERIT-KKK-^K-ISITEIKGVIVHRIETILF ^ ^ Attorney Docket No. VXH-00225 ^ (SEQ ID NO: 113). In some embodiments, the peptide immunogen is not or does not comprise (or the composition does not comprise) the amino acid sequence DAEFRHDSGYEVHH-^K-KKK-ISITEIKGVIVHRIETILF (SEQ ID NO: 88). In some embodiments, the peptide immunogen is not or does not comprise (or the composition does not comprise) the amino acid sequence DAEFRHDSGYEVHH-^K-KKKIITITRIITIITTID (SEQ ID NO: 89). In some embodiments, the peptide immunogen is not or does not comprise (or the composition does not comprise) the amino acid sequence ISITEIKGVIVHRIETILF- ^K-KKK-IKHVPGGGSVQIVYK (SEQ ID NO: 98). In some embodiments, the peptide immunogen is not or does not comprise (or the composition does not comprise) the amino acid sequence DHAGTYGLGD-KKK-^K-ISITEIKGVIVHRIETILF (SEQ ID NO: 100). In some embodiments, the peptide immunogen composition comprises the peptide immunogen in an amount from about 10 to 2000 µg / mL. In some embodiments, the peptide immunogen composition comprises the peptide immunogen in an amount from about 10 to about 1000 µg / mL. In some embodiments, the peptide immunogen composition comprises the peptide immunogen in an amount from about 10 to 500 µg / mL. In some embodiments, the peptide immunogen composition comprises the peptide immunogen in an amount from about 100 to 250 µg / mL. In some embodiments, the peptide immunogen composition comprises the peptide immunogen in an amount from about 10 to up to 2000 µg. In some embodiments, the peptide immunogen composition comprises the peptide immunogen in an amount from about 10 to about 1000 µg. In some embodiments, the peptide immunogen composition comprises the peptide immunogen in an amount from about 10 to 500 µg. In some embodiments, the peptide immunogen composition comprises the peptide immunogen in an amount from about 50 to 400 µg. In some embodiments, the peptide immunogen composition comprises the peptide immunogen in an amount from about 100 to 400 µg. In some embodiments, the peptide immunogen composition, when administered to a mammal induces production of IgG1 isotype antibodies to the target antigenic site or B cell epitope (e.g., wherein IgG1 antibody production is assessed from about week 1 to about week 12 after administration). In some embodiments, the peptide immunogen composition, when administered to a mammal induces substantially higher production of IgG antibodies than IgM antibodies to the target antigenic site or B cell epitope (e.g., wherein antibody production is assessed from about week 1 to about week 12 after administration). In some embodiments, the substantially higher is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher. In some embodiments, the IgG antibodies are of IgG1 isotype. In some embodiments, the peptide immunogen composition, when administered to a mammal substantially does not ^ ^ Attorney Docket No. VXH-00225 ^ induce production, or induces no detectable production, of IgM antibodies (e.g., wherein IgM antibody production is assessed from about week 1 to about week 12 after administration). In some embodiments, the peptide immunogen composition, when administered to a mammal induces substantially higher production of IgG1 isotype antibodies than IgG2, IgG3 and / or IgG4 isotype antibodies to the target antigenic site or B cell epitope (e.g., wherein antibody production is assessed from about week 1 to about week 12 after administration). In some embodiments, the substantially higher is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher. In some embodiments, the peptide immunogen composition, when administered to a mammal substantially does not induce production, or induces no detectable production, of IgG2, IgG3 and / or IgG4 isotype antibodies (e.g., wherein antibody production is assessed from about week 1 to about week 12 after administration). In some embodiments, the peptide immunogen composition, when administered to a mammal substantially does not induce, or induces no detectable, innate immunity (e.g., wherein the innate immunity is assessed from about week 1 to about week 12 after administration). The innate immunity can be assessed by any method known in the art or described herein. In some embodiments, the peptide immunogen composition, when administered to a mammal substantially does not induce, or induces no detectable, T cell inflammation (e.g., wherein the T cell inflammation is assessed from about week 1 to about week 12 after administration). In some embodiments, the assessment of any of these parameters can be made at week 6 to week 9 after administration. In some embodiments, the assessment of any of these parameters can be made at week 6 after administration of the peptide immunogen composition. In some embodiments, the assessment of any of these parameters can be made at week 9 after administration of the peptide immunogen composition. In some of these embodiments, the peptide immunogen composition is administered to a human or a non-human primate (i.e., the mammal is a human or non-human primate). In other embodiments, the mammal is an experimental animal, e.g., a mouse, a rat or a guinea pig. In some aspects, the present disclosure provides a method of inducing production of IgG1 antibodies but not IgM antibodies against a target antigenic site (e.g., a B cell epitope) in a subject in need thereof, comprising administering to the subject the peptide immunogen composition described herein. In some aspects, the present disclosure provides a method of inducing production of antibodies against a target antigenic site (e.g., a B cell epitope) in a subject suffering from, or at risk of, a disease or condition associated with, or caused by, a target antigen, comprising administering to the subject the peptide immunogen composition described herein. 7 ^ ^ Attorney Docket No. VXH-00225 ^ In some aspects, the present disclosure provides a method of treating or preventing a disease or condition associated with, or caused by, a target antigen, comprising administering to the subject the peptide immunogen composition described herein. In some embodiments, administering is parenteral. In some embodiments, administering is intramuscular. In some embodiments, administering is intradermal. In some embodiments, the disease or condition is a chronic disease or condition. In some embodiments, the disease or condition is an autoimmune disease or condition, a chronic inflammation, a neurodegenerative disease or condition, or an allergic disease or condition. In some embodiments, the disease or condition is cancer. In some embodiments, the method comprises administering the peptide immunogen composition to the subject over a period of time of at least or more than 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, or 15 years (e.g., multiple times over such period, such as at least 4, 6, 8, 10, 12, 15, 20, or 25 times over such period, or at least every 1 month, 2 months, 3 months, 4 months or 6 months). In some aspects, the present disclosure provides a method of inducing long-term production of antibodies against a target antigenic site (e.g., a B cell epitope), or preventing or treating a disease or condition associated with, or caused by, a target antigen, in a subject in need thereof, comprising administering a peptide immunogen composition to a subject over a period of time of at least or more than 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, or 15 years, wherein the peptide immunogen composition comprises a heterologous Th epitope linked to the target antigenic site (e.g., the B cell epitope), wherein the peptide immunogen composition does not comprise an adjuvant or comprises a compatible adjuvant in an amount up to about 1.6 mg / mL, wherein the compatible adjuvant is one or more aluminum salts. In some embodiments, the one or more aluminum salts is aluminum phosphate and / or aluminum hydroxide. In some embodiments, the target antigenic site (e.g., B cell epitope) does not comprise an endogenous Th epitope. In some embodiments, the disease or condition is a chronic disease or condition. In some embodiments, the disease or condition is an autoimmune disease or condition, a chronic inflammation, a neurodegenerative disease or condition, or an allergic disease or condition. In some embodiments, the disease or condition is cancer. In some embodiments, the peptide immunogen composition further comprises a polyanionic CpG oligonucleotide but does not comprise another adjuvant. In some embodiments, the peptide immunogen composition is any peptide immunogen composition described herein. In some embodiments of any of the methods described herein, administering comprises administering at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 ^ ^ Attorney Docket No. VXH-00225 ^ times to the subject. In some embodiments, administering comprises administering every 4 weeks to 6 months. In some embodiments, administering comprises administering every 8 weeks to 6 months. In some embodiments, administering comprises administering at least or about every 1 month. In some embodiments, administering comprises administering at least or about every 2 months. In some embodiments, administering comprises administering at least or about every 3 months. In some embodiments, administering comprises administering at least or about every 4 months. In some embodiments, administering comprises administering at least or about every 5 months. In some embodiments, administering comprises administering at least or about every 6 months. In some embodiments, administering comprises administering a priming regimen of 1 to 3 doses within about 4-12 weeks, such as within 4 weeks, 6 weeks, 8 weeks, 10 weeks or 12 weeks (e.g., followed by administering of a booster dose every 4 weeks to 6 months). In some embodiments, administering comprises administering a priming regimen of 1 to 3 doses within about 4-8 weeks, such as within 4 weeks, 6 weeks, or 8 weeks (e.g., followed by administering of a booster dose every 8 weeks to 6 months). In some embodiments, the priming regimen comprises 2 or 3 doses. In some embodiments, the priming regimen is administered at weeks 0, 3 and 6. In some embodiments, the priming regimen is followed by one boosting dose or multiple (e.g., at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 20) boosting doses (e.g., every 1, 2, 3, 4, 5, or 6 months). In some embodiments, the subject does not experience inflammation associated with the administration of the peptide immunogen composition. In some embodiments, the method does not comprise conjoint administration of an anti-inflammatory drug to counteract inflammation associated with administration of the peptide immunogen composition. In some embodiments, the method does not comprise administration of an anti-inflammatory drug conjointly with the peptide immunogen composition. In some embodiments, the method does not comprise administration of an anti-inflammatory drug at least daily, twice a week, once a week, or once in two weeks for at least 1 month, 2 months, 3 months, 4 months, 5 months or 6 months after administering the peptide immunogen composition. In some embodiments, the anti-inflammatory drug is a corticosteroid, a nonsteroidal anti- inflammatory drug (NSAID), an antileukotriene, and / or an immune selective anti- inflammatory derivative (ImSAID). In some embodiments of any of the methods described herein, the subject is a human. In some embodiments, administering the peptide immunogen composition induces production of IgG1 isotype antibodies to the target antigenic site (e.g., B cell epitope) in the subject (e.g., 9 ^ ^ Attorney Docket No. VXH-00225 ^ wherein IgG1 antibody production is assessed from about week 1 to about week 16 after administration). In some embodiments, administering the peptide immunogen composition induces substantially higher production of IgG antibodies than IgM antibodies to the target antigenic site (e.g., B cell epitope) in the subject (e.g., wherein antibody production is assessed from about week 1 to about week 16 after the administering). In some embodiments, the substantially higher is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher. In some embodiments, the IgG antibodies are of IgG1 isotype. In some embodiments, administering the peptide immunogen composition substantially does not induce production, or induces no detectable production, of IgM antibodies in the subject (e.g., wherein IgM antibody production is assessed from about week 1 to about week 16 after administration). In some embodiments, administering the peptide immunogen composition induces substantially higher production of IgG1 isotype antibodies than IgG2, IgG3 and / or IgG4 isotype antibodies to the target antigenic site (e.g., B cell epitope) in the subject (e.g., wherein antibody production is assessed from about week 1 to about week 16 after administration). In some embodiments, the substantially higher is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher. In some embodiments, administering the peptide immunogen composition substantially does not induce production, or induces no detectable production, of IgG2, IgG3 and / or IgG4 isotype antibodies in the subject (e.g., wherein antibody production is assessed from about week 1 to about week 16 after administration). In some embodiments, administering the peptide immunogen composition substantially does not induce, or induces no detectable, innate immunity in the subject (e.g., wherein the innate immunity is assessed from about week 1 to about week 16 after administration). The innate immunity can be assessed by any method known in the art or described herein. In some embodiments, administering the peptide immunogen composition substantially does not induce, or induces no detectable, T cell inflammation in the subject (e.g., wherein the T cell inflammation is assessed from about week 1 to about week 16 after administration). BRIEF DESCRIPTION OF FIGURES Figure 1 has graphs showing immunogenicity of the vaccine formulation with p4796kb, CpG1, and ADJU-PHOS® injected into Guinea pigs, rats, and monkeys. Figures 2A and 2B are graphs showing antibody responses of IgG (Figure 2A) and IgM (Figure 2B)^in rats following vaccination with p4796kb formulated in ADJU-PHOS® (AP) or ISA-51VG (ISA) over time^^arrows indicate injection points. ^ ^ Attorney Docket No. VXH-00225 ^ Figures 3A-3C are graphs showing IgG isotype titers from sera of rats vaccinated with p4796kb formulated in ADJU-PHOS® (AP) (Figure 3A), ISA-51VG (ISA) (Figure 3B), or from non-human primates (NHP) vaccinated with p4796kb formulated in ADJU- PHOS® (AP) (Figure 3C). Figures 4A-4B are graphs showing representative images of ELISpot assays of IFNgamma secretion from splenocytes collected from adjuvant control rats, p4796kb- vaccinated rats, or p5830kb-vaccinated rats, stimulated with Th epitope (UBITh1), corresponding CGRP B cell epitope, or the entire peptide immunogen, (Figure 4A) and quantification of spot count per million cells from the IFNgamma ELISpot of splenocytes from rats vaccinated with p4796kb and p5380kb compared to Adjuvant control (Figure 4B!^ data are presented as means + / - SEM. Figures 5A-5B are graphs showing binding potency (Figure 5A) and in vitro efficacy of inhibition of CGRP-induced cAMP stimulation in SK-N-MC cells (Figure 5B) of antibodies from guinea pigs vaccinated with p4796kb compared with the therapeutic mAb Galcanezumab. Figures 6A-6F are graphs showing antibody responses (Figures 6A, 6C, 6E) and LDL-C reductions (Figures 6B, 6D, 6F) in cynomolgus monkeys vaccinated with VXX-401 (which is a peptide immunogen composition comprising p5494kb peptide immunogen). Cynomolgus monkeys received 3 IM injections of 300 ug of p5494kb formulated with CpG3 (50 ug / dose) in ADJU-PHOS® (0.8 mg / dose) or ADJU-PHOS® adjuvant only at week 0, 3, and 6, and 3 IM injections of 300 ug of p5494kb formulated with CpG3 (50 ug / dose) in ISA51 VG (50% / dose) or ISA51 VG adjuvant only at week 13, 16 and 19, as indicated by arrows (Figures 6A, 6B). Cynomolgus monkeys received 3 or 4 IM injections of VXX-401 at 100 ug peptide immunogen or ADJU-PHOS® adjuvant only at week 0, 3, 6, and / or 24, as indicated by arrows (Figures 6C, 6D). Cynomolgus monkeys received 5 IM injections of VXX-401 at 100 ug peptide immunogen or ADJU-PHOS® adjuvant only on day 1, 22, 43, 64, and 85, as indicated by arrows (Figures 6E, 6F). VXX-401 was formulated with PCSK9 peptide immunogen (p5494kb), 200 "g / ml of CpG1, and 1.6 mg / ml of ADJU-PHOS®. Figures 7A-7E are graphs showing antibody responses (Figures 7A, 7D) and LDL-C reductions (Figures 7B, 7C, 7E) in cynomolgus monkeys vaccinated with p5494kb at ranging doses of peptide immunogens. Cynomolgus monkeys received 4 IM injections of VXX-401 at indicated doses of peptide immunogen, ADJU-PHOS® adjuvant only, or PBS control at week 0, 3, 6, and 24, as indicated by arrows (Figures 7A, 7B, 7C). Injection at week 24 restored anti-PCSK9 antibody titers and decreased LCL-C levels. Cynomolgus ^ ^ Attorney Docket No. VXH-00225 ^ monkeys received 5 IM injections of VXX-401 at 100 ug peptide immunogen or ADJU- PHOS® adjuvant only on day 1, 22, 43, 64, and 85, as indicated by arrows (Figures 7D, 7E). Antibody titers and LDL-C reductions were maintained. Figures 8A-8E are graphs showing PCSK9 binding potency comparing affinity purified antibodies from the 100 "g VXX-401 dosage group to evolocumab (Figure 8A), quantification of uptake of pHrodo-conjugated LDL-C in HepG2 cells + / - PCSK9 and the protective effect of affinity-purified VXX-401 antibodies (Figure 8B), and representative images of pHrodo-LDL-C uptake in HepG2 cells at baseline, with PCSK9 treatment, and rescue of uptake by VXX-401 derived antibodies (Figures 8C-8E).^VXX-401 induced the production of highly potent and functionally active anti-PCSK9 antibodies. Figures 9A-9B are graphs showing IgG and IgM responses (Figure 9A) and IgG isotype titers (Figure 9B) in monkeys treated with VXX-401 at 100 ug peptide.^VXX-401 induced an IgG1-dominant immune response. Figures 10A-10F are graphs showing quantification of spot count per million cells in ELISpot assays of IFNgamma and IL-4 secretions from PBMCs^collected from NHPs prior to (Figures 10A-10B) and post (Figures 10C-10D) immunization with VXX-401 at 100 ug peptide, and representative images of spot forming units (Figures 10E-10F). Figures 11A-11D are graphs showing quantification of spot count per million cells in ELISpot assays of IFNgamma and IL-4 secretions from PBMCs^collected from NHPs prior to (Figures 11A-11B) and post (Figures 11C-11D) immunization with VXX-401 at ranging peptide doses.^VXX-401 did not induce autoimmunity against endogenous PCSK9. DETAILED DESCRIPTION In certain aspects, provided herein are peptide immunogen compositions comprising a peptide immunogen comprising a T helper cell (Th) epitope (e.g., a heterologous Th epitope) linked to a target antigenic site (e.g., a B cell epitope), wherein the peptide immunogen composition does not comprise an adjuvant. In other aspects, provided herein are peptide immunogen compositions comprising a peptide immunogen comprising a Th epitope (e.g., a heterologous Th epitope) linked to a target antigenic site (e.g., a B cell epitope), wherein the peptide immunogen composition comprises an adjuvant in an amount of up to about 1.6 mg / mL, wherein the adjuvant is one or more aluminum salts. In some such embodiments, the one or more aluminum salts is aluminum phosphate and / or aluminum hydroxide. In some embodiments, the adjuvant is aluminum phosphate. In some embodiments, the adjuvant is present in an amount from about ^ ^ Attorney Docket No. VXH-00225 ^ 0.8 mg / mL to about 1.6 mg / mL, 1 mg / mL to 1.6 mg / mL, or 1.2 mg / mL to about 1.6 mg / mL. In some embodiments, the adjuvant is present in an amount of about or less than 0.8 mg / mL. In some embodiments, the B cell epitope does not comprise an endogenous Th epitope. In some embodiments, the B cell epitope does not comprise any Th epitope. In some embodiments, the Th epitope in the peptide immunogen described herein is a heterologous Th epitope. In some embodiments, the Th epitope is an artificial Th epitope. In some embodiments, the Th epitope is a promiscuous Th epitope. In some embodiments, the Th epitope is heterologous and promiscuous. In some embodiments, the Th epitope is artificial and promiscuous. In some embodiments, the peptide immunogens described herein comprise only one or more (e.g., 2) heterologous Th epitopes and do not comprise any endogenous Th epitope. In some embodiments, the peptide immunogens described herein further comprise a CpG oligonucleotide. In some embodiments, the peptide immunogen described herein does not comprise any adjuvant other than the aluminum salt adjuvant as described herein. Without being bound by any theory, the inventors found that the peptide immunogen compositions described herein induce a specific, targeted immune response. In particular, the peptide immunogen compositions described herein induce production of IgG antibodies against the target antigenic site, with no (no detectable) or low (not significant) IgM response in a mammal (e.g., a primate or a human). In some embodiments, the peptide immunogen compositions described herein induce no detectable IgM response in a mammal (e.g., a primate or a human). In some embodiments, the peptide immunogen compositions described herein induce production of specific IgG1 antibodies against the target antigenic site in a mammal. In some embodiments, the peptide immunogen compositions described herein do not induce production of IgG2, IgG3, and / or IgG4 antibodies against the target antigenic site in a mammal (e.g., a primate or a human). In certain aspects, described herein are methods of treatment and prevention, and uses, of the peptide immunogen compositions described herein. In some embodiments, the peptide immunogen compositions can be used for inducing production of IgG (e.g., IgG1) antibodies but no substantial or no detectable IgM antibodies against a target antigenic site in a subject. In some embodiments, the peptide immunogen compositions can be used for inducing production of IgG (e.g., IgG1) antibodies but not IgM antibodies against a target antigenic site in a subject. ^ ^ Attorney Docket No. VXH-00225 ^ In some embodiments, the peptide immunogen compositions can be used for inducing production of antibodies against a target antigenic site (e.g., a B cell epitope) by administering to a subject any peptide immunogen composition described herein comprising the target antigenic site. In some embodiments, the peptide immunogen compositions can be used for inducing production of antibodies against a target antigenic site (e.g., a B cell epitope) in a subject suffering from, or at risk of, a disease or condition associated with, or caused by the target antigen. The disease or condition can be any described herein or known in the art. In some embodiments, the disease or condition is an autoimmune disease or condition, a chronic inflammation, a neurodegenerative disease or condition, a chronic disease or condition, an allergic disease or condition, or a cancer. In some embodiments, the peptide immunogen compositions can be used for treatment or prevention of any disease or condition requiring repeated (e.g., at least 4, 5, 6, 7, 8, 9, or 10 times) administration of the compositions over a period of time (e.g., at least 1, 2, 3, 4, 5, 10, or 15 years or more). In some embodiments, the peptide immunogen compositions can be used for treatment or prevention of any disease or condition described herein. In some embodiments, the peptide immunogen compositions can be used for the treatment or prevention of a chronic disease (e.g., migraine, hypercholesterolemia or hyperlipidemia). In some embodiments, the peptide immunogen compositions can be used for the treatment or prevention of an autoimmune disease. In some embodiments, the peptide immunogen compositions can be used for the treatment or prevention of an allergic disease (e.g., atopic dermatitis). In some embodiments, the peptide immunogen compositions can be used for the treatment or prevention of a neurodegenerative disease (e.g., a synucleinopathy, a tauopathy, Alzheimer’s disease, or Parkinson’s disease). In some embodiments, the peptide immunogen compositions can be used for the treatment or prevention of cancer. In some embodiments, the subject treated in accordance with the methods described herein is a human. The examples set forth herein support the compositions and methods provided herein by demonstrating that, inter alia, the peptide immunogen compositions of the invention can elicit a specific humoral immune response to target antigenic sites. The examples also show that the peptide immunogen compositions provided herein induce no or low inflammation, non-specific immunogenicity or IgM antibody production, and specifically induce IgG1 antibodies against target antigenic sites. The examples further show that the peptide immunogen compositions provided herein are effective in inducing production of antibodies capable of inhibiting the activity of target antigens. 14 ^ ^ Attorney Docket No. VXH-00225 ^ Terminology Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The singular terms “a,” “an,” and “the” include plural referents unless context clearly indicates otherwise. In case of conflict, the present specification, including definitions of terms, will control. The term “about,” as used herein, refers to a range of + / - 10% of the stated value. In some embodiments, the range is + / - 5%, + / - 3%, + / - 2%, + / - 1%, + / - 0.5%, or + / - 0.1% of the stated value. The term “peptide immunogen,” as used herein, refers to peptides comprising an artificial T helper cell epitope covalently linked to a target antigenic site. The covalent linkage may be through a covalent peptide bond, thioester or a linker. In some embodiments, the linker is or comprises an amino acid sequence. The term “artificial,” as used herein in connection with the peptide immunogen or Th epitopes, refers to amino acid sequences that are not naturally occurring. The term “endogenous,” as used herein in connection with Th epitopes, refers to Th epitopes naturally occurring in the target protein or peptide. The term “promiscuous,” as used herein in connection with Th epitopes, refers to Th epitopes that are reactive across species and across individuals of a single species. The term “heterologous,” as used herein in connection with Th epitopes, refers to an amino acid sequence that is not part of, or not at least 80%, 85% or 90% homologous to, the wild-type amino acid sequence of the target protein or peptide or the target antigenic site (e.g., a B cell epitope). When a peptide immunogen comprises a “heterologous” Th epitope covalently linked to a B cell epitope of a target protein, the natural amino acid sequence of the B cell epitope is not extended in either the N-terminal or C-terminal directions to encompass the natural sequence of the Th epitope of the target protein, or a sequence at least 80%, 85% or 90% homologous thereto. The term “heterologous,” as used herein in connection with linkers, refers to an amino acid sequence that is not part of the wild-type amino acid sequence of the target antigenic site, such that the natural amino acid sequence of the target antigenic site is not extended in either the N-terminal or C-terminal directions of the target protein or peptide to create a linker. The term "preventing" a disease or condition in a subject, as used herein, refers to administering a medicament (e.g., the peptide immunogen construct described herein or an 15 ^ ^ Attorney Docket No. VXH-00225 ^ antibody elicited by such construct) to the subject prior to the onset of the disease or condition, when administration of the medicament to a statistical sample prior to the onset of the disease or condition reduces the occurrence of the disease or condition in the treated sample relative to an untreated control sample, or delays the onset or reduces the occurrence or severity of one or more symptoms of the disease or condition relative to the untreated control sample. The term “treating” a disease or condition in a subject, as used herein, refers to administering a medicament (e.g., the peptide immunogen construct described herein or an antibody elicited by such construct) to the subject having or suspected of having a disease or condition (i.e., after the onset of the disease or condition), such that at least one symptom of the disease or condition is decreased or prevented from worsening. Target Antigenic Sites In some aspects, the disclosure describes peptide immunogen compositions and methods that can be used to provide peptide immunogens that elicit antibodies to a desired target antigenic site. The target antigenic site can be a B cell epitope, a peptide hapten, a non- peptide hapten, or an immunologically reactive variant thereof. In some embodiments, the target antigenic site is a B cell epitope or a peptide hapten. In some embodiments, the target antigenic site comprises a B cell epitope or an immunologically reactive analogue thereof. In some embodiments, the target antigenic site comprises a peptide hapten. A peptide hapten is generally a peptide amino acid sequence that can specifically bind to an antibody but does not itself initiate antibody production^^In some embodiments, the target antigenic site comprises a non-peptide hapten. A non-peptide hapten can be any non-peptide low molecular weight compound, such as a carbohydrate, a nucleic acid, a lipid or a small molecule, that can specifically bind to an antibody but does not itself initiate antibody production. The target antigenic site can include any amino acid sequence from any target peptide or protein. In some embodiments, the target antigenic site is a peptide from a protein associated with or involved in pathogenesis of a disease or condition. In some embodiments, the target antigenic site comprises a self peptide (self-antigen), or an immunologically reactive analogue thereof. The target antigenic site can be a cancer or tumor antigen-related carbohydrate. In certain embodiments, the target antigenic site comprises any amino acid sequence from a self peptide or protein, such as a self-antigen. In some embodiments, the target antigenic site is taken from a tumor-associated neoantigen target that is normally ^ ^ Attorney Docket No. VXH-00225 ^ immunosilent. Examples of antigens or targets include, without limitation, amyloid ^ (A^) protein, A^, Tau, alpha-synuclein, CGRP, PCSK9, IgE, IL-6, IL-31, Amylin, Dipeptide protein, EMPD, LHRH, neoantigens. In certain embodiments, the target antigenic site comprises any peptide or protein sequence known in the art or described herein. Non- limiting, representative examples of target antigenic sites, including self-antigens and tumor- associated neoantigen sites are shown in Table 1. Other non-limiting, representative examples of target antigenic sites or B cell epitopes that can be used in the peptide immunogens described herein are disclosed in U.S. Pat. No^#^$^^^%^&^%^^^^^&&'^^^(^^^^)#*#^ Pat. Pub. Nos. US2022-^^%'^^^^^)*%^%'-^%^(&^(^^)*%^%^-^^'(^^$^^)*%^%^-^'^&(^^^^ US2022-^^&'^(%^^)*%^%'-^^^^^$^^^)*%^%'-^^$'^&(^^)*%^%^-0400634 or Int. Pat. Pub. +^^#^,-%^%'.^'^$^^^^,-%^%^.^^^^^^^^,-%^%^.^^(^$^, each of which is incorporated by reference herein in its entirety and specifically for the disclosure of target antigenic sites or B cell epitopes and peptide immunogens. In some embodiments, the target antigenic site is derived from portions of any one or more of: luteinizing hormone-releasing hormone (LHRH) (e.g., U.S. Pat. Nos.6,025,468, ^^%%(^$(&^^^^^^$^%(%^^^^^^)*^ / ^^^^^^^^^^^+^#^)*%^^&.^%^^^^(!^^^^0^^^^^^ (A^) (e.g., U.S. / ^^#^+^^#^^^$^^^^^$^^&^$^^^$^$^^(^%'%^'&'^^^^^^$^^^%^&^%!^^tau and amyloid ^ (A^) 1,-%^%^.^^(^$^!^^IgE (e.g., U.S. Pat. Nos.7,648,701 and 6,811,782)^ alpha-synuclein ( - Syn) (2^^^^^^^^^^^^^ / 3^^4^^#^+^#^ / 3^.)*%^^(.^'&$'(^^WO2018 / 232369^ US Publication No.2021 / 138049^ WO2023 / 034914)^ the extracellular membrane-proximal domain of membrane-bound IgE (or IgE EMPD) (International PCT Application No. PCT / US2017 / 069174)^ Tau (International PCT App. No. PCT / US2018 / 057840^^ ,-%^%^.^^^^^^^^WO2019 / 084488^^)*^ / ^^^^^^+^#^^^^&&'^^^()^^Interleukin-31 (IL-31) (International PCT Application No. PCT / US2018 / 065025)^^ / 3*5$^(International PCT Application No. PCT / US%^%^.^^^^%'^^,-%^%^.^^^$^&^^)*^ / ^^^^^^^^^^^+^#^ US2023 / 093678)^^367 / ^(International PCT Application No. / 3^.)*%^^$.^^$^^&^^ WO2020 / 142522^^)*^ / ^^^^^^^^^^^+^#^%^%%.^&'^(%)^ CETP for prevention and treatment of ^^^^^^^^^^^^^^^^^^24 / / ^14^0^^^!^^^^^^^^^^^^8^^^^^^^^^^^^^^^^^^^^^^^ type 2 diabetes (US2024- ^^^^^'^^^,-%^%^.^^'%'$!^^ / 434 / ^1)*%^%'-^^^^^$^^^,-%^%^.^^^$^^!^^^^^^^^^^^^^^^^^^^ proteins from C9ORF72 (US2021-^'^&(^^^^,-%^%^.^&%^%(!^^and any other peptide or protein sequence. Each of the target antigenic sites or B cell epitopes disclosed in the above- cited references is provided herein. More specifically, target antigenic sites or B cell epitopes include, without limitation, A^1-14(as described in U.S. Pat. No.9,102,752), -Syn126-135(as described in International PCT Application No. PCT / US2018 / 037938^^,-%^^(.%'%'^$^^)*^ 17 ^ ^ Attorney Docket No. VXH-00225 ^ Publication No.2021 / 138049), IgE EMPD1-39 (as described in International PCT Application No. PCT / US2017 / 069174), Tau379-408 (as described in International PCT Application No. PCT / US2018 / 057840^^,-%^^$.^(^^((^^)*^ / ^^^^^^+^#^^^^&&'^^^(), and IL-3197-144 (as described in International PCT Application No. PCT / US2018 / 065025), and others listed in Table 1. In some embodiments, the target antigenic site is derived from portions of CGRP as described in International PCT Application No. / 3^.)*%^^$.^^$^^&^^,-%^%^.^^%^%%^^)*^ Publication No.2022 / 073582. In some embodiments, the target antigenic site of CGRP is CGRP amino acids 28-37 or VPTNVGSKAF (SEQ ID NO: 51). In some embodiments, the target antigenic site is derived from portions of PCSK9 as described in International PCT Application No. PCT / US%^%^.^^^^%'^^,-%^%^.^^^$^&^^)*^ / ^^^^^^^^^^^+^#^ US2023 / 093678. In some embodiments, the target antigenic site is or comprises the amino acid sequence of EMPSEEGYQD of SEQ ID NO: 8 (which is from alpha-synuclein). In some embodiments, the target antigenic site is or comprises the amino acid sequence of VPTNVGSKAF of SEQ ID NO: 51 (which is from CGRP). In some embodiments, the target antigenic site is or comprises the amino acid sequence of SIPWNLERIT of SEQ ID NO: 55 (which is from PCSK9). In some embodiments, the target antigenic site is or comprises the amino acid sequence of DAEFRHDSGYEVHH of SEQ ID NO: 1 (which is from amyloid ^ protein). In some embodiments, the target antigenic site is or comprises the amino acid sequence of IKHVPGGGSVQIVYK of SEQ ID NO: 13 (which is from Tau protein). In some embodiments, the target antigenic site is or comprises the amino acid sequence of DHAGTYGLGD of SEQ ID NO: 15 (which is from Tau protein). In some embodiments, the target antigenic site is not or does not comprise the amino acid sequence EMPSEEGYQD (SEQ ID NO: 8). In some embodiments, the target antigenic site is not or does not comprise the amino acid sequence VPTNVGSKAF (SEQ ID NO: 51). In some embodiments, the target antigenic site is not or does not comprise the amino acid sequence SIPWNLERIT (SEQ ID NO: 55). In some embodiments, the target antigenic site is not or does not comprise the amino acid sequence DAEFRHDSGYEVHH (SEQ ID NO: 1). In some embodiments, the target antigenic site is not or does not comprise the amino acid sequence IKHVPGGGSVQIVYK (SEQ ID NO: 13). In some embodiments, the target antigenic site is not or does not comprise the amino acid sequence DHAGTYGLGD (SEQ ID NO: 15). ^ ^ Attorney Docket No. VXH-00225 ^ In some embodiments, the target antigenic site is not from SARS-COV-2. In some embodiments, the target antigenic site is not a receptor binding domain (RBD) of the S protein of a SARS-CoV-2 spike protein or a variant thereof. In some embodiments, the target antigenic site is a non-peptide hapten, including tumor associated carbohydrate antigens (TACA) and small-molecule drug compounds. Examples of TACAs include GD3, GD2, Globo-H, GM2, Fucosyl GM1, GM2, PSA, Ley, Lex, SLex, SLea, Tn, TF, and STn. In some embodiments, the target antigenic site (e.g., B cell epitope) does not comprise an endogenous Th epitope. In some embodiments, the target antigenic site (e.g., B cell epitope) does not comprise any Th epitope. The patents and patent publications referenced herein are specifically incorporated by reference herein in their entireties in respect to their disclosure of various target antigenic sites. T helper (Th) epitopes Evocation of a T helper cell response requires a T helper cell receptor to recognize a complex on the membrane of an antigen-presenting cell that is formed between a processed peptide fragment of a target antigen and an associated class II major histocompatibility complex (MHC). Thus, peptide processing of the target protein and three-way recognition are required for a T helper cell response. The immune responsiveness to a particular T helper cell (Th) epitope is, in part, determined by the MHC genes of the host, and the reactivity of Th epitopes differ among individuals of a population. In some embodiments, the Th epitope described herein allows for a broad MHC class II response. In certain embodiments, the peptide immunogens described herein comprise a target antigenic site (e.g., a B cell epitope) covalently linked to a Th epitope (e.g., heterologous Th epitope) directly or through a linker (e.g., heterologous linker). In some embodiments, any Th epitopes described herein can be used in peptide immunogens. In some embodiments, the Th epitope is artificial. Any artificial Th epitopes described herein can be used in peptide immunogens. In some embodiments, the Th epitope is promiscuous. Any promiscuous Th epitopes described herein can be used in peptide immunogens. In some embodiments, the Th epitope is artificial and promiscuous. Heterologous Th epitopes can enhance the immunogenicity of the target antigenic site and facilitate the production of specific high titer antibodies directed against it. The use of heterologous Th epitopes can contribute to reduction or avoidance of inflammation, such as T ^ ^ Attorney Docket No. VXH-00225 ^ cell-associated inflammation associated with use of endogenous Th epitopes in peptide immunogens. The use of heterologous Th epitopes in peptide immunogens can also contribute to reduction or avoidance of innate immune response. The use of heterologous Th epitopes in peptide immunogens can also contribute to induction of IgG-specific or IgG1- specific immune response. In some embodiments, the heterologous Th epitopes are artificial and / or promiscuous. The Th epitope can have an amino acid sequence derived from any species (e.g., human, pig, cattle, dog, rat, mouse, guinea pigs, etc.) or from a pathogen (e.g., a measles virus or a hepatis virus (e.g., a hepatitis virus surface protein, etc.). The Th epitope can also have promiscuous binding motifs to MHC class II molecules of multiple species. In certain embodiments, the Th epitope comprises multiple promiscuous MHC class II binding motifs to allow maximal activation of T helper cells leading to initiation and regulation of immune responses. The Th epitope is preferably immunosilent on its own, i.e., few or none of the antibodies generated by the peptide immunogens will be directed to the Th epitope, thus allowing a very focused immune response directed to the targeted antigenic site (e.g., B cell epitope). In some embodiments, a Th epitope is immunosilent, i.e., no detectable antibodies generated by the peptide immunogen that comprises it are directed to the Th epitope. Th epitopes can range in size from 10 to approximately 50 amino acid residues. In some embodiments, Th epitopes can have 15, 19, 20, 25, 30, 35, 40, 45 or 50 amino acid residues, or any range of amino acid residue numbers in between any of these values. The Th epitopes and disclosures of WO1999 / 066957, and corresponding US Patent No.6,713,301 are incorporated by reference herein in their entireties. The idealized artificial Th epitopes can also be modeled on the natural Th epitopes and “SSAL peptide prototypes” disclosed in WO1995 / 11998, incorporated by reference herein in its entirety. Any Th epitopes, and in particular artificial promiscuous Th epitopes, described in US Patent Publication No. US2022 / 0023400, incorporated by reference herein in its entire, can also be used in peptide immunogens described herein. Any Th epitopes, and in particular artificial promiscuous Th epitopes, described in US Patent Publication No. US2023 / 0218748, incorporated by reference herein in its entirety, can also be used in peptide immunogens described herein. In some embodiments, artificial Th epitopes of the disclosure are contiguous sequences of natural or non-natural amino acids that comprise a class II MHC molecule binding site, and are capable of enhancing or stimulating an antibody response to a target 20 ^ ^ Attorney Docket No. VXH-00225 ^ antigenic site when present in a peptide immunogen. In some embodiments, a Th epitope comprises discontinuous amino acid segments. In some embodiments, not every amino acid of a Th epitope is involved in MHC recognition. Th epitopes that can be used in peptide immunogens described herein include, but are not limited to, amino acid sequences derived from foreign pathogens, as exemplified in Table 2 (SEQ ID NOs: 19-47). Further, Th epitopes that can be used in peptide immunogens described herein include idealized artificial Th epitopes and combinatorial idealized artificial Th epitopes (e.g., SEQ ID NOs: 20 and 27-33). In some embodiments, the Th epitope is UBITh1. The heterologous Th epitope peptides presented as a combinatorial sequence (e.g., SEQ ID NOs: 28-31) contain a mixture of amino acid residues represented at specific positions within the peptide framework based on the variable residues of homologues for that particular peptide. An assembly of combinatorial peptides can be synthesized in one process by adding a mixture of the designated protected amino acids, instead of one particular amino acid, at a specified position during the synthesis process. Such combinatorial heterologous Th epitope peptide assemblies can allow broad Th epitope coverage for animals having a diverse genetic background. Representative combinatorial sequences of heterologous Th epitope peptides include SEQ ID NOs: 28-31, which are shown in Table 2. In some embodiments, the Th epitope used in peptide immunogens described herein has the amino acid sequence of SEQ ID NO: 30. In some embodiments, the Th epitope used in peptide immunogens described herein has the amino acid sequence of SEQ ID NO: 32. In some embodiments, the Th epitope used in peptide immunogens described herein has the amino acid sequence of SEQ ID NO: 33. In some embodiments, Th epitope peptides of the present disclosure provide broad reactivity and immunogenicity to animals and patients from genetically diverse populations. In some embodiments, promiscuous Th epitopes contain a Rothbard sequence, wherein the promiscuous Th epitope contains a charged residue followed by two to three hydrophobic residues, followed by a charged or polar residue (Rothbard and Taylor, EMBO 9^^^$((^^&:$'-101). Promiscuous Th epitopes can obey the 1, 4, 5, 8 rule, wherein a positively charged residue is followed by hydrophobic residues at the fourth, fifth and eighth positions, consistent with an amphipathic helix having positions 1, 4, 5 and 8 located on the same face. In some embodiments, the 1, 4, 5, 8 pattern of hydrophobic and charged and polar amino acids is repeated within a single Th epitope. In some embodiments, a promiscuous T cell ^ ^ Attorney Docket No. VXH-00225 ^ epitope contains one or more Rothbard sequence or an epitope that obeys the 1, 4, 5, 8 rule. In some embodiments, the Th epitope contains two or more Rothbard sequences. In some embodiments, Th epitopes comprise an additional charged residue Glu or Asp at position 1 to increase the charge surrounding the hydrophobic face of the Th. In some embodiments, the hydrophobic face of an amphipathic helix is maintained by hydrophobic residues at 2, 5, 8, 9, 10, 13 and 16. In some embodiments, amino acid residues at 2, 5, 8, 9, 10, and 13 are varied to provide a facade with the capability of binding to a wide range of MHC restriction elements. In some embodiments, the disclosed variations in amino acid residues can enlarge the range of immune responsiveness of the artificial Th epitopes. In some embodiments, the immunogenicity of the Th epitopes is improved by extending the N terminus with a non-polar and a polar uncharged amino acid, e.g., Ile and Ser, and extending the C terminus by a charged and hydrophobic amino acid, e.g., Lys and Phe. In some embodiments, the addition of a lysine residue or multiple lysine residues (e.g., KKK) to the Th epitopes improves the solubility of the peptide in water. In some embodiments, the C-terminus of the Th epitope is substituted by a common MHC-binding motif AxTxIL (see Meister et al, 1995, Vaccine 13(6):581-591). Th epitopes also include immunologically functional analogues of Th epitopes. Immunologically functional Th analogues include immune-enhancing analogs, cross-reactive analogs, and fragments of any of these Th epitopes that are sufficient to enhance or stimulate an immune response to the target antigenic site. Table 2 identifies another variation of a functional analogue for Th epitope peptide. In particular, SEQ ID NOs: 20 and 27 of MvF1 and MvF2 Th are functional analogues of SEQ ID NOs: 30 and 32 of MvF4 and MvF5 in that they differ in the amino acid frame by the deletion (SEQ ID NOs: 20 and 27) or the inclusion (SEQ ID NOs: 30 and 32) of two amino acids each at the N- and C-termini. The differences between these two series of analogous sequences would not affect the function of the Th epitopes contained within these sequences. Functional immunological Th analogues can, for example, include several versions of the Th epitope derived from Measles Virus Fusion protein MvF1-4 Ths (SEQ ID NOs: 20, 27, 28, 30, and 32) and from Hepatitis Surface protein HBsAg 1-3 Ths (SEQ ID NOs: 29, 31, and 33). The patents and patent publications referenced herein are incorporated by reference herein in their entireties, and specifically in respect to their disclosure of various Th epitopes. ^ ^ Attorney Docket No. VXH-00225 ^ Linkage between Th epitope and Target Antigenic Site In some embodiments, the peptide immunogens described herein comprise a Th epitope covalently linked to the target antigenic site (e.g., B cell epitope) via a linker. In other embodiments, the peptide immunogens described herein comprise a Th epitope covalently linked to the target antigenic site (e.g., B cell epitope) directly. In some embodiments, the peptide immunogens described herein comprise one or more linkers that covalently link the target antigenic site (e.g., B cell epitope) and one, two or more of the Th epitopes described herein. In some embodiments, the linker is heterologous. In some embodiments, the linker is not part of the wild type sequence of the target antigenic site (such as a B cell epitope). In some embodiments, the linker is not part of the wild type sequence of the target antigen (such as the target protein or peptide). In some embodiments, the natural amino acid sequence of the target antigenic site is not extended in either the N-terminal or C-terminal direction when the linker covalently links the target antigenic site and the Th epitope(s), because the linker is heterologous to the target antigenic site or the target antigen. The linker can be any molecule or chemical structure capable of linking two amino acids and / or peptides together. The linker can vary in length and polarity. The linker attachment can be through an amide- or carboxyl-linkage but other functionalities are possible as well. The linker can include a chemical compound, a naturally occurring amino acid, or a non-naturally occurring amino acid. Naturally occurring amino acids include alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. Non-naturally occurring amino acids include, but are not limited to, ^-N Lysine, ^- alanine, ornithine, norleucine, norvaline, hydroxyproline, thyroxine, ;-amino butyric acid, homoserine, citrulline, aminobenzoic acid, 6-aminocaproic acid (Aca; 6-aminohexanoic acid), hydroxyproline, mercaptopropionic acid (MPA), 3-nitro-tyrosine, pyroglutamic acid, and the like. In some embodiments, the linker comprises or consists of an amino acid sequence. In some embodiments, the linker has at least 1, at least 2, at least 3, or at least 4 amino acids (e.g., where at least one, two, three or all amino acids are lysine). In some embodiments, the linker has less than 6 or 5 amino acids. In some embodiments, the linker has 3 amino acids (e.g., where at least one, two, or all three amino acids are lysine). In some embodiments, the linker has 4 amino acids (e.g., where at least one, two, or all three amino acids are lysine). ^ ^ Attorney Docket No. VXH-00225 ^ In certain embodiments, the heterologous linker comprises or consists of one naturally occurring amino acid or non-naturally occurring amino acid. In other embodiments, the linker contains more than one naturally occurring and / or non-naturally occurring amino acid (e.g., the linker is a peptide). The linker can provide structural features to the peptide immunogen construct. In particular, the linker can provide physical separation between the Th epitope and the antigenic site (e.g., B cell epitope). Such physical separation can disrupt any artificial secondary structures created by the proximity of the Th epitope to the B cell epitope. Additionally, such physical separation can eliminate interference between the Th cell and B cell responses. Furthermore, the linker can be designed to create or modify a secondary structure of the peptide immunogen. In some embodiments, a linker is designed to act as a flexible hinge. A flexible hinge can enhance the separation of Th and B cell epitopes and / or permit more efficient interactions between the presented peptide immunogen and the appropriate T helper and B cells to enhance the immune response to the B cell epitope. Non- limiting examples of sequences of flexible hinges are found in the immunoglobulin heavy chain hinge region, which are often proline rich. One particularly useful flexible hinge that can be used as a linker is provided by the sequence Pro-Pro-Xaa-Pro-Xaa-Pro (SEQ ID NO: 131), where Xaa is any amino acid, for example, aspartic acid. The linker can also provide functional features to the peptide immunogen. For example, the spacer can be designed to change the overall charge of the peptide immunogen, which can affect the solubility of the peptide immunogen. Changing the overall charge of the peptide immunogen can also affect the ability of the peptide immunogen to associate with other compounds and reagents. For example, the overall charge of the peptide immunogen is important for the formation of stable immunostimulatory complexes described herein. In some embodiments, the linker comprises or consists of one of the following amino acids: Lys-, Gly-, Lys-Lys-Lys-, ( , ^-N)Lys, Lys-Lys-Lys-^Lys (SEQ ID NO: 129), ^-N-Lys- Lys-Lys-Lys (SEQ ID NO: 130), and Pro-Pro-Xaa-Pro-Xaa-Pro (SEQ ID NO: 131), wherein Xaa is any amino acid or is aspartic acid. In some embodiments, the linker comprises or consists of the amino acid sequence Lys-Lys-Lys, ^-Lys-Lys-Lys-Lys (SEQ ID NO: 130) or Lys-Lys-Lys-^-Lys (SEQ ID NO: 129).^^In some embodiments, the sequence of the spacer comprises or consists of ^-Lys-Lys-Lys-Lys (SEQ ID NO: 130) or Lys-Lys-Lys-^-Lys (SEQ ID NO: 129). In some embodiments, the heterologous linker is Lys-Lys-Lys-^Lys (SEQ ID NO: 129). In some embodiments, the heterologous linker is ^Lys-Lys-Lys-Lys (SEQ ID NO: 130)^^ ^ ^ Attorney Docket No. VXH-00225 ^ As is understood in the art, for a construct including ^-Lys as or within a linker, the C- terminus of a first peptide sequence is conjugated to the epsilon amino group of the lysine to form a first amide bond, and the N-terminus of a second peptide sequence is conjugated to the carboxyl group of the lysine to form a second amide bond. The structure of the Lys- ^-Lys (K-^K) linkage is shown below: In other embodiments, a bifunctional chemical compound is used as a linker. Such chemical compounds include, but are not limited to, (2-aminoethoxy) acetic acid (AEA), 5- aminovaleric acid (AVA), 6-aminocaproic acid (Ahx), 8-amino-3,6-dioxaoctanoic acid (AEEA, mini-PEG1), 12-amino-4,7,10-trioxadodecanoic acid (mini-PEG2), 15-amino- 4,7,10,13-tetraoxapenta-decanoic acid (mini-PEG3), trioxatridecan-succinamic acid (Ttds), 12-amino-dodecanoic acid, Fmoc-5-amino-3-oxapentanoic acid (O1Pen), and the like. The linker in peptide immunogens can be covalently linked at either N- or C-terminal end of the Th epitope. Similarly, the linker in peptide immunogens can be covalently linked at either N- or C-terminal end of the antigenic site (e.g., B cell epitope). In some embodiments, the linker is covalently linked to the C-terminal end of the Th epitope and to the N-terminal end of the B cell epitope. In other embodiments, the linker is covalently linked to the C-terminal end of the B cell epitope and to the N-terminal end of the Th epitope. In certain embodiments, more than one linker can be used, for example, when more than one Th epitope is present in the peptide immunogen. When more than one linker is used, each linker can be the same or different. Additionally, when more than one Th epitope is present in the peptide immunogen, the Th epitopes can be separated with a linker, which can be the same as, or different from, the linker used to separate the Th epitope from the B cell epitope. There is no limitation in the arrangement of the linker in relation to the Th epitope or the B cell epitope. Peptide Immunogens Provided herein are peptide immunogens comprising a Th epitope covalently linked to a target antigenic site (e.g., B cell epitope). In some embodiments, the Th epitope is ^ ^ Attorney Docket No. VXH-00225 ^ covalently linked to the target antigenic site directly. In other embodiments, the Th epitope is covalently linked to the target antigenic site through a linker. In some embodiments, provided herein are peptide immunogens comprising a heterologous Th epitope covalently linked to the target antigenic site (e.g., B cell epitope) via a heterologous linker. In some embodiments, the peptide immunogen does not comprise an endogenous Th epitope. In some embodiments, the peptide immunogen does not comprise any Th epitope other than the heterologous Th epitope. In some embodiments, the peptide immunogen comprises one heterologous Th epitope, such as any heterologous Th epitope described herein (which can be an artificial and / or promiscuous Th epitope). In some embodiments, the peptide immunogen comprises more than one heterologous Th epitope. The Th epitope in the peptide immunogens described herein can be covalently linked at either N- or C-terminal end of the target antigenic site (e.g., B cell epitope). In some embodiments, the Th epitope is covalently linked to the N-terminal end of the target antigenic site (e.g., B cell epitope). In other embodiments, the Th epitope is covalently linked to the C- terminal end of the target antigenic site (e.g., B cell epitope). In certain embodiments, more than one Th epitope is covalently linked to the target antigenic site (e.g., B cell epitope). When more than one Th epitope is linked to the target antigenic site (e.g., B cell epitope), each Th epitope can have the same amino acid sequence or different amino acid sequences. In addition, when more than one Th epitope is linked to the target antigenic site (e.g., B cell epitope), the Th epitopes can be arranged in any order. For example, the Th epitopes can be consecutively linked to the N-terminal end of the target antigenic site (e.g., B cell epitope), or consecutively linked to the C-terminal end of the target antigenic site (e.g., B cell epitope), or a Th epitope can be covalently linked to the N-terminal end of the target antigenic site while a separate Th epitope is covalently linked to the C-terminal end of the target antigenic site. There is no limitation in the arrangement of the Th epitopes in relation to the target antigenic site. In some embodiments, the peptide immunogen is represented by, essentially consists of or consists of the formula (Th)m-(A)n-(B)-X or (B)-(A)n-(Th)m-X, wherein Th is the heterologous T helper epitope^ m is from 1, 2, 3 or 4 (e.g., m is 1)^ A is an amino acid of a linker^^n is from 0 to 10 (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10), e.g., n is 1^ B is the target antigenic site (e.g., a B cell epitope), X is an -COOH or -CONH2of an amino acid (i.e., the peptide immunogen has or does not have an amide at the C-terminus). In some embodiments, m is 1 or 2. In some embodiments, n is 1 to 4 (e.g., 3 or 4). In some embodiments, the target antigenic site (e.g., a B cell epitope) comprises 6 to 50 contiguous amino acid residues of a 26 ^ ^ Attorney Docket No. VXH-00225 ^ target antigenic protein, e.g., 8 to 15 contiguous amino acid residues of a target antigenic protein. In some embodiments, the B cell epitope is any B cell epitope described herein. In some embodiments, the Th epitope is any Th epitope described herein. In some embodiments, (A)nis any linker described herein. In some embodiments, the peptide immunogen or a B cell epitope is acetylated (e.g., on the N-terminus). In some embodiments, the B cell epitope is cyclized (using any bridge, linkage or methodology known in the art or described herein, e.g., due to the presence of cysteine residues naturally occurring in the B cell epitope sequence or inserted by substitution of a naturally occurring residue). In some embodiments, the peptide immunogen does not comprise any other epitope, peptide and / or protein sequence that is not part of the formulae. In other embodiments, the peptide immunogens described herein is represented, essentially consists of, or consists of the formula: (A)n-(Target antigenic site)-(B)o-(Th)m-X or (A)n-(B)o -(Th)m-(B)o-(Target antigenic site)-X or (A)n-(Th)m-(B)o-(Target antigenic site)-X or (Target antigenic site)-(B)o -(Th)m-(A)n-X or (Th)m-(B)o-(Target antigenic site)-(A)n-X, wherein: ^^^^^4^^^^^^^^^^^^^^^^0^^^^^^^^^^^^^^^ each B is independently an amino acid, -NHCH(X)CH2SCH2CO-, - NHCH(X)CH2SCH2CO(EN)Lys-, -NHCH(X)CH2S-succinimidyl(EN)Lys-, or - NHCH(X)CH2S-(succinimidyl)-^ each Th is independently an artificial Th cell epitope, an analog, or segment thereof, each Target antigenic site is a B cell epitope, a peptide hapten, or an immunologically reactive analogue ^^^^^^^^ X is -COOH or -CONH2 group (of the C-terminal amino acid)^ n is 0, 1, 2, 3, 4, 5, 6, 7, (^^$^^^^^^^^ ^^^^^^^^%^^'^^^^^^^^^^^ o is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. ^ ^ Attorney Docket No. VXH-00225 ^ In some embodiments, the Th epitope, the target antigenic site and / or the linker can be any of those described herein. The peptide immunogens described herein can comprise about or less than 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, or about 100 amino acid residues. In some embodiments, the peptide immunogens described herein can comprise about or less than 20, about 30, about 40, about 50, about 60, about 70, or about 80 amino acid residues. Non-limiting, representative examples of peptide immunogens that can be used in the peptide immunogen compositions and methods described herein are shown in Table 4. Other non-limiting, representative examples of peptide immunogens that can be used in the peptide immunogen compositions and methods described herein are disclosed in U.S. Pat. Nos. $^^^%^&^%^^^^^&&'^^^(^^^^)#*#^Pat. Pub. Nos. US2022-^^%'^^^^^)*%^%'-^%^(&^(^^)*%^%^- ^^'(^^$^^)*%^%^-^'^&(^^^^)*%^%%-^^&'^(%^^)*%^%'-^^^^^$^^^)*%^%'-^^$'^&(^^ US2024-^^^^^'^^^^^2^^#^ / ^^#^ / ^^#^+^^#^,-%^%'.^'^$^^^^,-%^%^.^^^^^^^^ WO2024 / 158596, each of which is incorporated by reference herein in its entirety and specifically for the disclosure of peptide immunogens and their constituent parts. For example, and without limitation, peptide immunogens disclosed in Tables 5-7 of US2023- 0218748 and WO2020 / 132275 are specifically provided herein. In some embodiments, the peptide immunogens for use in the present invention are any of those disclosed in US Pat.9,102,752, Pat. Pubs. US2014-0271690 or WO2014 / 143087 (amyloid beta peptide immunogens)^^Pat. Pubs. US2022-0023400 or WO2019 / 213555^^ US2023-0218748 or WO2020 / 132275^^WO2023 / 034914 (alpha-synuclein peptide immunogens)^^WO2024 / 015611 (tau peptide immunogen)^^WO2024 / 158596 (tau and amyloid beta peptide immunogens)^^US2021-0138049 or WO2018 / 232369 (alpha-synuclein peptide immunogens)^^US Pat.11,773,148, US2021-0101948, or WO2019 / 084488 (tau peptide immunogens)^^US2021-0347866 or WO2020 / 072428 (dipeptide repeat proteins from C9ORF72 peptide immunogens)^^US2022-0073582 or WO2020 / 142522 (CGRP peptide immunogens)^^US2023-0146694 or WO2021 / 150910 (PACAP peptide immunogens)^^ US2023-0093678 or WO2021 / 154947 (PCSK9 peptide immunogens)^^and / or US2024- 0400634 or WO2021 / 163239 (IAPP peptide immunogens). In some embodiments, a peptide immunogen is selected from any one or more listed in Table 4. In some embodiments, a peptide immunogen is a tau B cell epitope-containing peptide immunogen provided in Table 4. In some embodiments, a peptide immunogen is an alpha-synuclein B cell epitope- containing peptide immunogen provided in Table 4. In some embodiments, a peptide ^ ^ Attorney Docket No. VXH-00225 ^ immunogen is an amyloid beta B cell epitope-containing peptide immunogen provided in Table 4. In some embodiments, a peptide immunogen is a CGRP B cell epitope-containing peptide immunogen provided in Table 4. In some embodiments, a peptide immunogen is a PACAP B cell epitope-containing peptide immunogen provided in Table 4. In some embodiments, a peptide immunogen is a IAPP B cell epitope-containing peptide immunogen provided in Table 4. In some embodiments, a peptide immunogen is a PCSK9 B cell epitope- containing peptide immunogen provided in Table 4. In some embodiments, the peptide immunogen is or comprises the amino acid sequence ISITEIKGVIVHRIETILF-^K-KKK-EMPSEEGYQD (SEQ ID NO: 92). In some embodiments, the Th epitope, the ^K-KKK linker and / or the B cell epitope of the peptide immunogen can be substituted by another, e.g., another known in the art or described herein (e.g., another alpha-synuclein B epitope, another linker described herein, or another Th epitope). In other embodiments, the peptide immunogen is not or does not comprise the amino acid sequence ISITEIKGVIVHRIETILF-^K-KKK-EMPSEEGYQD (SEQ ID NO: 92). In some embodiments, the peptide immunogen is or comprises the amino acid sequence ISITEIKGVIVHRIETILF-^K-KKK-VPTNVGSKAF (SEQ ID NO: 107). In some embodiments, the Th epitope, the ^K-KKK linker and / or the B cell epitope of the peptide immunogen can be substituted by another, e.g., another known in the art or described herein (e.g., another CGRP B epitope, another linker described herein, or another Th epitope). In other embodiments, the peptide immunogen is not or does not comprise the amino acid sequence ISITEIKGVIVHRIETILF-^K-KKK-VPTNVGSKAF (SEQ ID NO: 107). In some embodiments, the peptide immunogen is or comprises the amino acid sequence SIPWNLERIT-KKK-^K-ISITEIKGVIVHRIETILF (SEQ ID NO: 113). In some embodiments, the Th epitope, the KKK-^K linker and / or the B cell epitope of the peptide immunogen can be substituted by another, e.g., another known in the art or described herein (e.g., another PCSK9 B epitope, another linker described herein, or another Th epitope). In other embodiments, the peptide immunogen is not or does not comprise the amino acid sequence SIPWNLERIT-KKK-^K-ISITEIKGVIVHRIETILF (SEQ ID NO: 113). In some embodiments, the peptide immunogen is or comprises the amino acid sequence DAEFRHDSGYEVHH-^K-KKK-ISITEIKGVIVHRIETILF (SEQ ID NO: 88). In some embodiments, the Th epitope, the ^K-KKK linker and / or the B cell epitope of the peptide immunogen can be substituted by another, e.g., another known in the art or described herein (e.g., another amyloid beta B epitope, another linker described herein, or another Th ^ ^ Attorney Docket No. VXH-00225 ^ epitope). In other embodiments, the peptide immunogen is not or does not comprise the amino acid sequence DAEFRHDSGYEVHH-^K-KKK-ISITEIKGVIVHRIETILF (SEQ ID NO: 88). In some embodiments, the peptide immunogen is or comprises the amino acid sequence ISITEIKGVIVHRIETILF-^K-KKK-IKHVPGGGSVQIVYK (SEQ ID NO: 98). In some embodiments, the Th epitope, the ^K-KKK linker and / or the B cell epitope of the peptide immunogen can be substituted by another, e.g., another known in the art or described herein (e.g., another Tau B epitope, another linker described herein, or another Th epitope). In other embodiments, the peptide immunogen is not or does not comprise the amino acid sequence ISITEIKGVIVHRIETILF-^K-KKK-IKHVPGGGSVQIVYK (SEQ ID NO: 98). In some embodiments, the peptide immunogen is or comprises the amino acid sequence DHAGTYGLGD-KKK-^K-ISITEIKGVIVHRIETILF (SEQ ID NO: 100). In some embodiments, the Th epitope, the KKK-^K linker and / or the B cell epitope of the peptide immunogen can be substituted by another, e.g., another known in the art or described herein (e.g., another Tau B epitope, another linker described herein, or another Th epitope). In other embodiments, the peptide immunogen is not or does not comprise the amino acid sequence DHAGTYGLGD-KKK-^K-ISITEIKGVIVHRIETILF (SEQ ID NO: 100). The patents and patent publications referenced herein are specifically incorporated by reference herein in their entireties in respect to their disclosure of various peptide immunogens. Peptide Immunogen and Adjuvant Compositions In some embodiments, described herein are pharmaceutical compositions comprising any peptide immunogen described herein and an adjuvant. In some embodiments, the adjuvant is an aluminum adjuvant. In some embodiments, the adjuvant is an aluminum salt. In some embodiments, the aluminum salt is aluminum phosphate (ADJU-PHOS®) or AlPO4. In some embodiments, the aluminum salt is aluminum hydroxide (ALHYDROGEL®) or Al(OH)3. In some embodiments, the aluminum salt is potassium aluminum sulfate. In some embodiments, the aluminum salt is aluminum oxyhydroxide or AlOOH. In some embodiments, the aluminum salt is aluminum hydroxyphosphate or Al(OH)x(PO4)y. In some embodiments, the aluminum salt is aluminum hydroxyphosphate sulfate (AAHS). In some embodiments, described herein are pharmaceutical compositions comprising any peptide immunogen described herein and two or more adjuvants. In some embodiments, the two or more adjuvants are aluminum salts. In some embodiments, the adjuvant is a ^ ^ Attorney Docket No. VXH-00225 ^ mixture of aluminum salts. In some embodiments, the aluminum salts are aluminum phosphate (ADJU-PHOS®) and aluminum hydroxide (ALHYDROGEL®). In some embodiments, the peptide immunogens are adsorbed to aluminum gels. In some embodiments, the peptide immunogen is precipitated with an aluminum adjuvant. An adjuvant may enhance or prolong the immune response to the peptide immunogen (without eliciting an antigenic response on its own). In some embodiments, an adjuvant described herein facilitates or mediates induction of a specific immune response against the target antigenic site. In some embodiments, an adjuvant described herein facilitates or mediates induction of a specific IgG-based or IgG1-based immune response against the B cell epitope with no or low IgM or innate immunity. In some embodiments, the pharmaceutical compositions described herein do not comprise an adjuvant. In some embodiments, the pharmaceutical composition that does not comprise any adjuvant facilitates or mediates induction of a specific immune response against the target antigenic site. In some embodiments, the pharmaceutical composition that does not comprise any adjuvant facilitates or mediates induction of a specific IgG-based or IgG1- based immune response against the B cell epitope with no or low IgM or innate immunity. In some embodiments, the pharmaceutical compositions described herein comprise the adjuvant (such as the compatible adjuvant) described herein in the amount up to about 0.1 mg / mL, 0.2 mg / mL, 0.3 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, 0.7 mg / mL, 0.8 mg / mL, 0.9 mg / mL, 1 mg / mL, 1.1 mg / mL, 1.2 mg / mL, 1.3 mg / mL, 1.4 mg / mL, 1.5 mg / mL or 1.6 mg / mL, or any value in between the stated values. In some embodiments, the pharmaceutical compositions described herein comprise the adjuvant described herein in the amount up to about 1.6 mg / mL, or up to about 0.8 mg / mL. In some embodiments, the pharmaceutical compositions described herein comprise aluminum salt in the amount up to about 1.6 mg / mL, or up to about 0.8 mg / mL. In some embodiments, the pharmaceutical compositions described herein comprise aluminum salt adjuvant in an amount of about 0.8 mg / mL to about 1.6 mg / mL. In some embodiments, the pharmaceutical compositions described herein comprise aluminum salt adjuvant in an amount from about 0.1 mg / mL to about or less than 0.8 (or to about or less than 0.7) mg / mL. In some embodiments, the pharmaceutical compositions described herein comprise aluminum phosphate in the amount up to about 1.6 mg / mL, or up to about 0.8 mg / mL. In some embodiments, the pharmaceutical compositions described herein comprise aluminum hydroxide in the amount up to about 1.6 mg / mL, or up to about 0.8 mg / mL. In some embodiments, the pharmaceutical compositions described herein comprise aluminum salt adjuvant in an amount of about 0.8 mg / mL to about 31 ^ ^ Attorney Docket No. VXH-00225 ^ 1.6 mg / mL. In some embodiments, the pharmaceutical compositions described herein comprise aluminum phosphate adjuvant in an amount of about 0.8 mg / mL to about 1.6 mg / mL. In some embodiments, the pharmaceutical compositions described herein comprise aluminum hydroxide adjuvant in an amount of about 0.8 mg / mL to about 1.6 mg / mL. In some embodiments, the pharmaceutical compositions described herein comprise aluminum salt adjuvant in the amount of about 1.6 mg / mL. In some embodiments, the pharmaceutical compositions described herein comprise aluminum phosphate adjuvant in the amount of about 1.6 mg / mL. In some embodiments, the pharmaceutical compositions described herein comprise aluminum hydroxide adjuvant in the amount of about 1.6 mg / mL. In some embodiments, the pharmaceutical compositions described herein comprise aluminum phosphate (as an adjuvant) in the amount up to about 0.1 mg / mL, 0.2 mg / mL, 0.3 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, 0.7 mg / mL, 0.8 mg / mL, 0.9 mg / mL, 1 mg / mL, 1.1 mg / mL, 1.2 mg / mL, 1.3 mg / mL, 1.4 mg / mL, 1.5 mg / mL or 1.6 mg / mL, or any value in between the stated values. Peptide Immunogen and Anionic Molecule / CpG Compositions In some embodiments, the pharmaceutical compositions described herein comprise a peptide immunogen and an anionic molecule (e.g., an anionic oligonucleotide or an anionic polynucleotide). In some embodiments, the pharmaceutical composition comprises a peptide immunogen, and an anionic oligonucleotide or polynucleotide. In some embodiments, the anionic oligonucleotide or polynucleotide is CpG oligonucleotide. In some embodiments, the peptide immunogen is cationic or positively charged at a pH in the range of 5.0 to 8.0, or has a portion that is cationic or positively charged. In some embodiments, the peptide immunogen (or a portion thereof) has a positive charge of at least <^^^^^^^^^^^^^^^^<^^^^^^^^^^^^<%^^^^^^^^^^^^^^^<%^^^^^^^^^^^<'^^^^^^^^^^^^^^^<'#^^^^^^^^^^^^^^^^ calculated by assigning +1 charge for each lysine (K), arginine (R) or histidine (H), a -1 charge for each aspartic acid (D) or glutamic acid (E), and a charge of 0 to other amino acids of the amino acid sequence. In some embodiments, the anionic molecule is negatively charged at a pH in the range of 5.0 to 8.0. In some embodiments, the anionic molecule has a negative charge of at least -1, or more than -^^^^^^^^^^^^-2, or more than -%^^^^^^^^^^^-3, or more than -3. The charge is calculated by assigning -1 charge for each phosphodiester or phosphorothioate group in the molecule. ^ ^ Attorney Docket No. VXH-00225 ^ In some embodiments, the pharmaceutical composition comprises a peptide immunogen and an anionic oligonucleotide (e.g., a CpG oligonucleotide). In some embodiments, a peptide immunogen and an anionic oligonucleotide (e.g., a CpG oligonucleotide) complex is in the form of particles. The size of particles can be in the range from 1 to 50 microns. In some embodiments, said particles are capable of providing “adjuvantation” and upregulation of a specific immune response in vivo. However, as used herein, an anionic molecule such as an anionic oligonucleotide, and in particular CpG, is not referred to as an “adjuvant.” In other words, the term “adjuvant,” as used herein does not encompass an anionic oligonucleotide such as CpG. In some embodiments, the pharmaceutical composition comprises CpG1, CpG2, and / or CpG3. In some embodiments, the pharmaceutical composition comprises a CpG1 oligonucleotide. In some embodiments, the pharmaceutical composition comprises a CpG2 oligonucleotide. In some embodiments, the pharmaceutical composition comprises a CpG3 oligonucleotide. In some embodiments, the CpG oligonucleotide acts as a peptide immunogen stabilizer. In some embodiments, the peptide immunogen and CpG oligonucleotide are in the form of a particulate. In some embodiments, the peptide immunogen and CpG oligonucleotide are formulated as a suspension. In some embodiments, the pharmaceutical composition comprises a single stranded oligonucleotide with 8 to 64 nucleotide bases, with the number of repeats of CpG motif in the range of 1 to 10. In some embodiments, the pharmaceutical composition comprises a single stranded oligonucleotide with 8 to 48 nucleotide bases, with the number of repeats of CpG motif in the range of 3 to 8. In some embodiments, the pharmaceutical composition comprises an anionic oligonucleotide 5’-X1-C-G-X2-3’, wherein C and G are u^^^^^0^^^^^^^ =^^^^^^^^^^^^^^^^^^^^^^^^^^^14!^^^^^^^^^^16!^^^^^^^0^^^^^1^!^^^^^^=%^^^^^0^^^^^^^13!^^^^ thymine (T). In some embodiments, the pharmaceutical composition comprises an anionic oligonucleotide 5’-X1-C-G-(X2)2-'>^^?^^^^^^^3^^^^^6^^^^^^^^^^^0^^^^^^^=^^^^^^^^^^^^^^^^^^^ ^^^^^^^^14!^^^^^^^^^^16!^^^^^^^0^^^^^1^!^^^^^^=%^^^^^0^^^^^^^13!^^^^^^0^^^^^1^!# In some embodiments, a composition comprising a peptide immunogen and an anionic molecule (e.g., CpG) further comprises an adjuvant as described herein. In some embodiments, the pharmaceutical compositions described herein do not comprise an anionic molecule (e.g., an anionic oligonucleotide or an anionic polynucleotide). In some embodiments, the pharmaceutical compositions described herein do not comprise CpG1, CpG2 and / or CpG3. In some embodiments, the pharmaceutical compositions described herein do not comprise CpG1. In some embodiments, the pharmaceutical ^ ^ Attorney Docket No. VXH-00225 ^ compositions described herein do not comprise CpG2. In some embodiments, the pharmaceutical compositions described herein do not comprise CpG3. In some embodiments, the CpG oligonucleotide is as described in WO 03 / 068169, which is incorporated by reference herein in its entirety and specifically as it relates to CpG oligonucleotides. In some embodiments, the CpG comprises or consists of a sequence of CpG1 (tcgtcgtttt gtcgttttgt cgttttgtcg tt^^*@A^2B^+-:^(^), CpG2 (tcgtcgtttt gtcgttttgt cgtt^^*@A^ ID NO: 82), or CpG3 (tcgtcgtttt gtcgttttgt cgtt^^*@A^2B^+-:^('). In some embodiments, the CpG oligonucleotide (e.g., CpG1, CpG2, or CpG3) is a phosphorothioate oligonucleotide. In some embodiments, CpG1 comprises the sequence of 5’ TCgTCgTTTTgTCgTTTTgTCgTTTTgTCgTT 3’ (SEQ ID NO: 81), which is fully phosphorothioated. Non-limiting examples of CpG oligonucleotides are provided in Table 3. Immunostimulatory complexes between peptide immunogens and CpG oligonucleotides are in the form of particles with a size typically in the range from 1-50 microns (depending on factors including the relative charge stoichiometry and molecular weight of the interacting species). Such stabilized immunostimulatory complexes are suitable for preparing pharmaceutical compositions by various processes including water-in-oil emulsions, mineral salt suspensions, and polymeric gels. In some embodiments, CpG oligonucleotide (e.g., CpG1) is present in the peptide immunogen compositions described herein in an amount up to about 300 µg / mL. In some embodiments, CpG oligonucleotide (e.g., CpG1) is present in the peptide immunogen compositions described herein in an amount up to about 200 µg / mL. In some embodiments, CpG oligonucleotide (e.g., CpG1) is present in the peptide immunogen compositions described herein in an amount about 100 µg / mL to about 200 µg / mL. In some embodiments, CpG oligonucleotide (e.g., CpG1) is present in the peptide immunogen compositions described herein in an amount of about 200 µg / mL. In some embodiments, CpG oligonucleotide (e.g., CpG1) is present in the peptide immunogen compositions described herein in an amount of about or less than 100 µg / mL. In some embodiments, CpG oligonucleotide (e.g., CpG1) is present in the peptide immunogen compositions described herein in an amount of about or less than150 µg / mL. Pharmaceutical Peptide Immunogen Compositions In some embodiments, described herein are pharmaceutical compositions comprising any peptide immunogen described herein and a pharmaceutically acceptable carrier, excipient or another additive. The specific adjuvants and CpG oligonucleotides for use in the ^ ^ Attorney Docket No. VXH-00225 ^ pharmaceutical compositions described herein are discussed in other sections of this application. In some embodiments, the pharmaceutical compositions described herein comprise a stabilizing agent, a diluent, a preservative, a solubilizing agent, or a buffer. The appropriate pharmaceutically acceptable carrier and delivery system can be determined by a skilled artisan. In some embodiments, the pharmaceutical composition comprises Tween® 80 (Polysorbate 80 or Polyoxyethylene (2)) sorbitan monooleate. In some embodiments, the pharmaceutical composition is a mineral salt suspension. In some embodiments, the pharmaceutical composition is a gel. In some embodiments, the pharmaceutical composition is a polymeric gel. In some embodiments, the pharmaceutical composition is a wet gel suspension. In some embodiments, the pharmaceutical composition is a water-in-oil emulsion. In some embodiments, the pharmaceutical composition is a water-in-oil-in-water (i.e., w / o / w) emulsion. In some embodiments, the pharmaceutical composition described herein comprises a peptide immunogen and a CpG oligonucleotide. In some embodiments, the pharmaceutical composition comprises a peptide immunogen, a CpG oligonucleotide and a mineral salt. In some embodiments, the pharmaceutical composition comprises a peptide immunogen, a CpG oligonucleotide, and a gelling polymer. In some embodiments, the pharmaceutical composition comprises a peptide immunogen, a CpG oligonucleotide, a mineral salt and a gelling polymer. In some embodiments, the pharmaceutical composition described herein comprises a peptide immunogen, an adjuvant described herein (such as in the amount described herein), and optionally a CpG oligonucleotide. In some embodiments, the pharmaceutical composition comprises a peptide immunogen, an adjuvant described herein, optionally a CpG oligonucleotide, optionally one or more excipients (such as inactive or inert excipients), and optionally no adjuvant. In some embodiments, the pharmaceutical composition comprises no excipients. In some embodiments, the pharmaceutical composition comprises a peptide immunogen, an adjuvant described herein or no adjuvant, a CpG oligonucleotide or no CpG oligonucleotide, and if any excipient then only one or more inactive or inert excipients. In some embodiments, the pharmaceutical composition described herein does not comprise any adjuvant. In some embodiments, the pharmaceutical composition described herein does not comprise an aluminum salt-based adjuvant. In some embodiments, the pharmaceutical composition described herein that comprises no adjuvant induces a specific ^ ^ Attorney Docket No. VXH-00225 ^ immune response against the target antigenic site. In some embodiments, the pharmaceutical composition described herein that comprises no adjuvant induces a specific IgG-based or IgG1-based immune response against the B cell epitope with no or low IgM or innate immunity. In some embodiments, the pharmaceutical composition described herein does not comprise any adjuvant but comprises a CpG oligonucleotide. In some embodiments, the pharmaceutical composition described herein does not comprise any adjuvant and does not comprise a CpG oligonucleotide. In some embodiments, the pharmaceutical composition described herein comprises a peptide immunogen in a saline solution, optionally a CpG oligonucleotide, optionally one or more excipients (such as inactive or inert excipients), and optionally no adjuvant. In some embodiments, the pharmaceutical composition described herein does not comprise a CpG oligonucleotide irrespective of whether any adjuvant is present. In some embodiments, the pharmaceutical composition described herein comprises a CpG oligonucleotide irrespective of whether any adjuvant is present. In some embodiments, the peptide immunogen, the adjuvant described herein, and optionally a CpG oligonucleotide are the only components of the pharmaceutical composition that effect specificity (specificity against the target antigenic site and / or a specific IgG-based or IgG1-based immune response against the B cell epitope with no or low IgM or innate immunity), safety or efficacy of the pharmaceutical composition. In some embodiments, the pharmaceutical composition comprises, essentially consists of, or consists of: a peptide immunogen as described herein, an adjuvant as described herein, optionally a CpG oligonucleotide as described herein, and excipients (e.g., inert or clinically inert excipients). In some embodiments, the pharmaceutical compositions described herein do not comprise an adjuvant other than the adjuvants described herein (in particular, aluminum salt-based adjuvants). In other embodiments, the pharmaceutical compositions described herein may comprise another adjuvant (in particular, not an aluminum salt-based adjuvant) if the identity or amount of such other adjuvant does not interfere with the ability of the pharmaceutical composition to induce a specific IgG-based or IgG1-based immune response against the target antigenic site with no or low IgM or innate immunity. In such other embodiments, the pharmaceutical compositions described herein may comprise another adjuvant in addition to an aluminum salt-based adjuvant described herein, if the identity or amount of such other adjuvant does not interfere with the ability of the pharmaceutical composition to induce a specific IgG-based or IgG1-based immune response against the target antigenic site with no ^ ^ Attorney Docket No. VXH-00225 ^ or low IgM or innate immunity. In yet other embodiments, the pharmaceutical compositions described herein may comprise another adjuvant, and not comprise an aluminum salt-based adjuvant described herein, if the identity or amount of such other adjuvant does not interfere with the ability of the pharmaceutical composition to induce a specific IgG-based or IgG1- based immune response against the target antigenic site with no or low IgM or innate immunity. In some embodiments, the pharmaceutical compositions described herein do not comprise a mineral oil. In some embodiments, the pharmaceutical compositions described herein do not comprise Montanide™ISA-51VG. In some embodiments, the pharmaceutical compositions described herein do not comprise a squalene-based adjuvant. In some embodiments, the pharmaceutical compositions described herein do not comprise AddaVax™. In some embodiments, the pharmaceutical composition described herein is an immediate release formulation. In some embodiments, the pharmaceutical composition described herein is a sustained release formulation. The pharmaceutical compositions described herein may comprise excipients suitable for induction of systemic or localized mucosal immunity. The pharmaceutical compositions described herein can be formulated as liquid solutions or suspensions for administration by injection. In some embodiments, the pharmaceutical compositions are formulated for parenteral administration. In some embodiments, the pharmaceutical compositions are formulated for intravenous (IV), subcutaneous (SC), intramuscular (IM), intradermal (ID), or intraperitoneal (IP) administration. In some embodiments, the pharmaceutical compositions are formulated for intramuscular (IM) administration. In some embodiments, the pharmaceutical compositions are formulated for intranasal administration. In some embodiments, the pharmaceutical compositions are formulated for oral administration. In some embodiments, the pharmaceutical compositions described herein comprise an effective amount of the peptide immunogen, e.g., an amount effective to elicit an immune response (such as production of antibodies) against the B cell epitope. In some embodiments, the pharmaceutical compositions described herein comprise an effective amount of the adjuvant, e.g., an amount effective to elicit specific antibodies against the B cell epitope, in particular IgG1 antibodies, while eliciting no or low IgM antibodies (e.g., eliciting no detectable IgM antibodies) or innate immune response. ^ ^ Attorney Docket No. VXH-00225 ^ In some embodiments, the pharmaceutical compositions are formulated in a suitable dosage unit form (e.g., in a fixed dose composition). In some embodiments, the pharmaceutical composition comprises from about 10 µg to about 2 mg of the peptide immunogen. In some embodiments, the pharmaceutical composition comprises from about 10 µg to about 1 mg of the peptide immunogen. In some embodiments, the pharmaceutical composition comprises from about 10 µg to about 0.5 mg of the peptide immunogen. In some embodiments, the pharmaceutical composition comprises from about 10 to 2000 µg / mL of the peptide immunogen. In some embodiments, the pharmaceutical composition comprises from about 10 to about 1000 µg / mL of the peptide immunogen. In some embodiments, the pharmaceutical composition comprises from about 10 to 500 µg / mL of the peptide immunogen. In some embodiments, the pharmaceutical composition comprises from about 100 to 250 µg / mL of the peptide immunogen. In some embodiments, the pharmaceutical composition comprises from about 50 to 500 µg of the peptide immunogen. In some embodiments, the pharmaceutical composition comprises from about 100 to 400 µg of the peptide immunogen. In some embodiments, the pharmaceutical composition comprises from about 100 to 300 µg of the peptide immunogen. In some embodiments, the pharmaceutical composition comprises about 300 µg of the peptide immunogen. Effective doses of the peptide immunogen vary depending on a variety of factors, including means of administration, target site, patient (including age, weight and general health), concurrently administered medications, and the purpose of administration. In some embodiments, the pharmaceutical compositions comprise more than one peptide immunogen. Methods of Making Also described herein are methods of producing the peptide immunogens described herein. The peptide immunogen constructs of the disclosure can be made using chemical synthesis methods that are well known in the art (see, e.g., Fields et al., Chapter 3 in Synthetic Peptides: A User’s Guide, ed. Grant, W. H. Freeman & Co., New York, NY, 1992, p.77). For example, the peptide immunogen constructs can be synthesized using the automated Merrifield techniques of solid phase synthesis with the -NH2protected by either t-Boc or F-moc chemistry using side chain protected amino acids on, for example, an Applied Biosystems Peptide Synthesizer Model 430A or 431. Preparation of peptide immunogen constructs comprising combinatorial library peptides for Th epitopes can be accomplished by ^ ^ Attorney Docket No. VXH-00225 ^ providing a mixture of alternative amino acids for coupling at a given variable position. After complete assembly of a desired peptide immunogen construct, the resin can be treated according to standard procedures to cleave the peptide from the resin and the functional groups on the amino acid side chains can be deblocked. The free peptide can be purified by HPLC and characterized biochemically, for example, by amino acid analysis or by sequencing. The quality of peptides produced by this chemical process can be controlled and defined and, as a result, reproducibility of peptide immunogen constructs, immunogenicity, and yield can be assured. In some embodiments, the Th epitope(s) and B cell epitope(s) of the peptide immunogen are produced simultaneously in a single solid-phase peptide synthesis, in tandem. The peptide immunogen constructs can also be made using recombinant DNA technology including using nucleic acid molecules, vectors, and / or host cells. As such, nucleic acid molecules encoding the peptide immunogens described herein and immunologically functional analogues thereof are also encompassed by the present disclosure. Similarly, vectors, including expression vectors, comprising nucleic acid molecules as well as host cells containing the vectors are also encompassed by the present disclosure. In some embodiments, the longer synthetic peptide immunogens are synthesized by well-known recombinant DNA techniques. For example, methods can include a step of incubating a host cell containing an expression vector containing a nucleic acid molecule encoding a peptide immunogen under such conditions where the peptide is expressed. Such techniques are provided in well-known standard manuals with detailed protocols. To construct a gene encoding a peptide immunogen described herein, the amino acid sequence is reverse translated to obtain a nucleic acid sequence encoding the amino acid sequence, preferably with codons that are optimum for the organism in which the gene is to be expressed. Next, a synthetic gene is made typically by synthesizing oligonucleotides which encode the peptide and any regulatory elements, if necessary. The synthetic gene is inserted in a suitable cloning vector and transfected into a host cell. The peptide is then expressed under suitable conditions appropriate for the selected expression system and host. Purification and characterization methods for peptides are well known to those skilled in the art. ^ ^ Attorney Docket No. VXH-00225 ^ Methods for manufacturing of immunostimulatory complexes In some embodiments, the peptide immunogen compositions described herein include immunostimulatory complexes comprising peptide immunogens and CpG oligodeoxynucleotide (ODN) molecules. Stabilized immunostimulatory complexes (ISC) are derived from a cationic portion of the peptide immunogen and a polyanionic CpG ODN molecule. The self-assembling system is driven by electrostatic neutralization of charge. Stoichiometry of the molar charge ratio of cationic portion of the peptide immunogen construct to anionic oligomer determines extent of association. The non-covalent electrostatic association of peptide immunogen and CpG ODN is a reproducible process, and the complexes are easily characterized for quality control during manufacturing. The peptide / CpG ODN immunostimulatory complex aggregates, which facilitate presentation to the “professional” antigen-presenting cells (APC) of the immune system thus further enhancing of the immunogenicity of the complexes. The peptide / CpG ISC are well tolerated in vivo. In some embodiments, the CpG ODN in the peptide immunogen compositions described herein is 100% bound to the peptide immunogen in a process mediated by electrostatic neutralization of opposing charge, resulting in the formation of micron-sized particulates. In some embodiments, the CpG ODN in the peptide immunogen compositions described herein is at least 70%, 75%, 80%, 85%, 90%, or 95% bound to the peptide immunogen. The particulate form allows for a significantly reduced dosage of CpG from the conventional use of CpG adjuvants, which can lead to less potential for adverse innate immune responses. Characteristics and Advantages of the Peptide Immunogen Compositions The peptide immunogen compositions described herein induce (when administered to a mammal, e.g., a mouse, a rat, a primate, or a human) production of specific antibodies to target antigenic sites (e.g., B cell epitopes). In some embodiments, the produced antibodies are primarily or exclusively IgG antibodies. In some embodiments, at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% of the total amount of the produced antibodies are IgG antibodies (e.g., as measured after isolation of the anti-B cell epitope antibodies from the mammal). In some embodiments, the produced antibodies are primarily or exclusively IgG1 antibodies. In some embodiments, at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% of the total amount of the produced antibodies are IgG1 antibodies (e.g., as measured after isolation of the anti-B cell ^ ^ Attorney Docket No. VXH-00225 ^ epitope antibodies from the mammal). In some embodiments, very low or no IgM antibodies are produced after administration of the peptide immunogen compositions described herein. In some embodiments, less than 25%, 20%, 15%, 10%, 5%, 3%, 2% or 1% of the total amount of the antibodies produced after administration of the peptide immunogen compositions described herein are IgM antibodies (e.g., as measured after isolation of the anti-B cell epitope antibodies from the mammal). In some embodiments, low or no IgG2, IgG3 and / or IgG4 antibodies are produced after administration of the peptide immunogen compositions described herein. In some embodiments, less than 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 3%, 2% or 1% of the total amount of the antibodies produced after administration of the peptide immunogen compositions described herein are IgG2, IgG3 and / or IgG4 antibodies (e.g., as measured after isolation of the anti-B cell epitope antibodies from the mammal). In some embodiments, low or no IgG2 antibodies are produced. In some embodiments, low or no IgG3 antibodies are produced. In some embodiments, low or no IgG4 antibodies are produced. “No” antibodies in this context means that such antibodies are not detected or not detectable. In some of these embodiments, the B cell epitope is from CGRP. In some of these embodiments, the B cell epitope is from PCSK9. In some of these embodiments, the B cell epitope is from Tau. In some of these embodiments, the B cell epitope is from ^ amyloid protein. In some of these embodiments, the B cell epitope is from synuclein. In some embodiments, the levels of various antibodies, immune responses and cytokines referenced herein are compared between those before administration to a subject and after administration to the subject of the peptide immunogen compositions described herein. In some embodiments, the levels of various antibodies, immune responses and cytokines referenced herein are compared between those elicited by the peptide immunogen compositions described herein and those elicited by the same compositions without the peptide immunogen present. In some embodiments, the peptide immunogen compositions described herein do not induce substantial or any innate immunity (when administered to a mammal, e.g., a mouse, a rat, a primate, or a human) as measured by any means known in the art or described herein. In some embodiments, the peptide immunogen compositions described herein do not induce substantial or any inflammation or T cell inflammation (when administered to a mammal, e.g., a mouse, a rat, a primate, or a human) as measured by any means known in the art or described herein. ^ ^ Attorney Docket No. VXH-00225 ^ In some embodiments, the peptide immunogen compositions described herein do not increase production of inflammatory cytokines (e.g., any one, two, three, four, five or more of: IFN;, IL-1^, IL-4, IL-5, IL-6, IL-10, IL-13, KC / Gro and TNF- ) when administered to a mammal (e.g., a mouse, a rat, a primate, or a human) as measured by any means known in the art or described herein. In some embodiments, the peptide immunogen compositions described herein demonstrate target binding potency (when administered to a mammal, e.g., a mouse, a rat, a primate, or a human) similar (i.e., within 50%, 25% or 10%) to a monoclonal antibody against the target. For example, peptide immunogen compositions comprising a CGRP B cell epitope, such as those described herein, demonstrate anti-CGRP binding potency (when administered to a mammal, e.g., a mouse, a rat, a primate, or a human) similar (i.e., within 50%, 25% or 10%) to available (e.g., marketed) monoclonal antibodies against CGRP. In another example, peptide immunogen compositions comprising a PCSK9 B cell epitope, such as those described herein, demonstrate anti-PCSK9 binding potency (when administered to a mammal, e.g., a mouse, a rat, a primate, or a human) similar (i.e., within 50%, 25% or 10%) to available (e.g., marketed) monoclonal antibodies against CGRP. In some embodiments, the peptide immunogen compositions described herein demonstrate anti-target activity potency (when administered to a mammal, e.g., a mouse, a rat, a primate, or a human) similar (i.e., within 50%, 25% or 10%) to a monoclonal antibody against the target. For example, peptide immunogen compositions comprising a CGRP B cell epitope, such as those described herein, demonstrate anti-CGRP activity potency (when administered to a mammal, e.g., a mouse, a rat, a primate, or a human) similar (i.e., within 50%, 25% or 10%) to available (e.g., marketed) monoclonal antibodies against CGRP. In another example, peptide immunogen compositions comprising a PCSK9 B cell epitope, such as those described herein, demonstrate anti-PCSK9 activity potency (when administered to a mammal, e.g., a mouse, a rat, a primate, or a human) similar (i.e., within 50%, 25% or 10%) to available (e.g., marketed) monoclonal antibodies against CGRP. In some embodiments, the activity potency is the level of efficacy in blocking or inhibiting the function of the target antigen. In some embodiments, the activity potency is the level of efficacy in blocking or inhibiting a biological effect (e.g., a symptom of a disease or condition) associated with or caused by the target antigen. In some embodiments, the peptide immunogen compositions described herein induce robust antibody titers against the target antigen. In some embodiments, the peptide immunogen compositions described herein induce, or induce exclusively, target antigen- ^ ^ Attorney Docket No. VXH-00225 ^ specific antibody production. In some embodiments, the peptide immunogen compositions described herein induce primarily, or induce exclusively, humoral immune response. In some of these embodiments, the B cell epitope is from CGRP. In some of these embodiments, the B cell epitope is from PCSK9. In some of these embodiments, the B cell epitope is from Tau. In some of these embodiments, the B cell epitope is from ^ amyloid protein. In some of these embodiments, the B cell epitope is from alpha-synuclein. In some embodiments, peptide immunogen compositions described herein, when administered to a mammal, induce production of IgG antibodies to the target antigenic site (e.g., B cell epitope) of the peptide immunogen. In some embodiments, the IgG antibodies are of IgG1 isotype. In some embodiments, peptide immunogen compositions described herein, when administered to a mammal, induce substantially higher production of IgG (e.g., IgG1) antibodies than IgM antibodies to the B cell epitope (e.g., at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher). In some embodiments, peptide immunogen compositions described herein, when administered to a mammal, substantially do not induce production, or induce no detectable production, of IgM antibodies. In some embodiments, peptide immunogen compositions described herein, when administered to a mammal, induce substantially higher production of IgG1 isotype antibodies than IgG2, IgG3 and / or IgG4 isotype antibodies to the B cell epitope (e.g., at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher). In some embodiments, peptide immunogen compositions described herein, when administered to a mammal, substantially do not induce production, or induce no detectable production, of IgG2, IgG3 and / or IgG4 isotype antibodies. In some embodiments, antibody production is assessed about 1-12 weeks post-administration (e.g., in an animal model). In some embodiments, antibody production is assessed about 3 weeks post-administration. In some embodiments, antibody production is assessed about 6 weeks post-administration. In some embodiments, antibody production is assessed about 9 weeks post-administration. In some embodiments, administering of the peptide immunogen compositions described herein to a human induces production of IgG1 isotype antibodies to the B cell epitope. In some embodiments, administering of the peptide immunogen compositions described herein to a human induces substantially higher production of IgG (e.g., IgG1) antibodies than IgM antibodies to the B cell epitope (e.g., at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher). In some embodiments, administering of the peptide immunogen compositions described herein to a human induces substantially does not induce production, or induces no detectable production, of IgM antibodies. In some embodiments, administering of the peptide immunogen compositions described herein to a human induces substantially ^ ^ Attorney Docket No. VXH-00225 ^ higher production of IgG1 isotype antibodies than IgG2, IgG3 and / or IgG4 isotype antibodies to the B cell epitope (e.g., at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher). In some embodiments, administering of the peptide immunogen compositions described herein to a human substantially does not induce production, or induces no detectable production, of IgG2, IgG3 and / or IgG4 isotype antibodies. In some embodiments, administering of the peptide immunogen compositions described herein to a human substantially does not induce, or induces no detectable, innate immunity or T cell inflammation in the subject. In some embodiments, antibody production is assessed about 1-16 weeks post-administration (e.g., in a human subject). In some embodiments, antibody production is assessed about 3 weeks post- administration. In some embodiments, antibody production is assessed about 6 weeks post- administration. In some embodiments, antibody production is assessed about 9 weeks post- administration. In some embodiments, antibody production is assessed about 12 weeks post- administration. Antibodies Also provided herein is an antibody elicited by any of peptide immunogens described herein, or an antigen-binding (e.g., B cell epitope binding) fragment thereof. In some embodiments, provided herein is an isolated (and, optionally, purified) antibody elicited by any of peptide immunogens described herein, or an antigen-binding (e.g., B cell epitope binding) fragment thereof. In some embodiments, such antibodies are IgG antibodies. In some embodiments, such antibodies are IgG1 antibodies. In some embodiments, such antibodies are substantially free of IgM antibodies. In some embodiments, such antibodies are substantially free of IgG2, IgG3 and / or IgG4 isotype antibodies. In some embodiments, the antibodies elicited by the peptide immunogens described herein comprise substantially higher portion of IgG1 isotype antibodies (to the target antigenic site or B cell epitope) than IgM antibodies, where the substantially higher is at least 10, 15 or 20 times higher. In some embodiments, the antibodies elicited by the peptide immunogens described herein comprise substantially higher portion of IgG1 isotype antibodies than IgG2, IgG3 and / or IgG4 isotype antibodies (to the target antigenic site or B cell epitope), where the substantially higher is at least 5, 6, 7, 8, 9, 10, 15 or 20 times higher. Also provided herein are isolated antibodies, or epitope-binding fragments thereof, that specifically bind to the antigenic site (e.g., B cell epitope) of the disclosed peptide immunogens. In some embodiments, such antibodies are IgG antibodies. In some embodiments, such antibodies are IgG1 antibodies. ^ ^ Attorney Docket No. VXH-00225 ^ Antibodies for use in therapy can be generated using standard methods in the art and include, e.g., monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific and trispecific antibodies), and antibody fragments, provided that the desired antigen-binding activity and specificity is maintained. Antibody fragments include, for example, Fv, single-chain Fv (scFv), Fab, Fab’, di-scFv, sdAb (single domain antibody), and (Fab’)2(including a chemically linked F(ab’)2). Antibodies also include, e.g., chimeric antibodies, humanized antibodies, and antibodies of various species such as mouse, human, cynomolgus monkey, etc. In certain embodiments, provided herein are methods of making antibodies (such as IgG, in particular IgG1 antibodies), or epitope-binding fragments thereof, that specifically bind to the antigenic site (e.g., B cell epitope) of the disclosed peptide immunogens. In some embodiments, such methods comprise administering (e.g., parenterally, e.g., intramuscularly) a peptide immunogen to a subject (e.g., a mammal, such as a mouse, a rat, a non-human primate, or a human). In some embodiments, such methods further comprise, after a period of time sufficient to generate antibodies (e.g., at from about week 1 to about week 16 post- administration, or about week 6, week 9 and / or week 12 post-administration), recovering and isolating produced antibodies (such as IgG1 antibodies to the B cell epitope). Methods of Use The peptide immunogen compositions described herein are useful for eliciting an immune response to the target antigenic site or B cell epitope as described herein, particularly for eliciting IgG1 antibodies to the target antigenic site or B cell epitope. The peptide immunogen compositions described herein are useful in many diverse medical and veterinary applications. In certain aspects, any disease or condition can be treated or prevented using the peptide immunogen compositions described herein. In some aspects, the peptide immunogen compositions described herein are particularly useful against diseases and conditions which require chronic or long-term administration of such compositions, such as repeated administration over a period of time, e.g., at least or more than 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 times. A period of time can be over 6 months or more, e.g., at least 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, 7 years, 10 years, 12 years, 15 years, 20 years, or over a patient’s life time. In some aspects, the peptide immunogen compositions described herein are particularly useful against diseases and conditions which require administration to patients who are at risk of inflammation, e.g., chronic inflammation. Without being bound by any ^ ^ Attorney Docket No. VXH-00225 ^ theory, the peptide immunogen compositions described herein can act specifically against the target antigenic site and do not induce, or substantially do not induce, an IgM response or innate immunity. Furthermore, the peptide immunogen compositions described herein can act to induce specific humoral, and in particular IgG1 response (e.g., inducing production of robust titers of IgG1 antibodies specific to the target antigenic site in the treated patient). In some embodiments, the disease or condition treated or prevented in accordance with the methods described herein is a chronic disease or condition. In some embodiments, the disease or condition treated in accordance with the methods described herein is an allergic disease or condition. In some embodiments, the disease or condition treated in accordance with the methods described herein is an autoimmune disease or condition. In some embodiments, the disease or condition treated in accordance with the methods described herein is cancer. In some embodiments, the disease or condition treated in accordance with the methods described herein is a neurodegenerative disease or condition. In some embodiments, the disease or condition treated in accordance with the methods described herein is tauopathy or Alzheimer’s. In such embodiments, the target antigen can be tau and / or ^ amyloid protein. Suitable target antigenic sites of these proteins are known in the art. For example, target antigenic sites (e.g., B cell epitopes) of these proteins described herein can be used in design of the peptide immunogen suitable for the treatment or prevention of tauopathy or Alzheimer’s. In some embodiments, the disease or condition treated in accordance with the methods described herein is synucleinopathy, Parkinson’s, dementia with Lewy bodies (DLB), or multiple system atrophy (MSA). In such embodiments, the target antigen can be - synuclein protein. Suitable target antigenic sites of -synuclein are known in the art. For example, target antigenic sites (e.g., B cell epitopes) of -synuclein described herein can be used in design of the peptide immunogen suitable for the treatment or prevention of such diseases. In some embodiments, the disease or condition treated in accordance with the methods described herein is migraine. In such embodiments, the target antigen can be CGRP. Suitable target antigenic sites of CGRP are known in the art. For example, target antigenic sites (e.g., B cell epitopes) of CGRP described herein can be used in design of the peptide immunogen suitable for the treatment or prevention of migraine. In some embodiments, the disease or condition treated in accordance with the methods described herein is hypercholesterolemia. In such embodiments, the target antigen can be PCSK9. Suitable target antigenic sites of PCSK9 are known in the art. For example, ^ ^ Attorney Docket No. VXH-00225 ^ target antigenic sites (e.g., B cell epitopes) of PCSK9 described herein can be used in design of the peptide immunogen suitable for the treatment or prevention of hypercholesterolemia or hyperlipidemia. In other embodiments, the disease or condition treated or prevented in accordance with the methods described herein is a disease or condition that does not require or may not require long-term or chronic administration of the peptide immunogen compositions. In other embodiments, the disease or condition treated or prevented in accordance with the methods described herein can be any disease or condition that may benefit from use of a composition that does not induce an IgM response, innate immunity or T cell inflammation, and that does induce production of specific IgG1 antibodies to the target antigenic site. In some embodiments, the disease or condition is not COVID or caused by SARS-COV-2. In some embodiments, provided herein are methods of inducing production of antibodies against a B cell epitope in a subject suffering from, or at risk of, any disease or condition (e.g., an autoimmune disease or condition, a chronic inflammation, a neurodegenerative disease or condition, a chronic disease or condition, or an allergic disease or condition, a cancer) comprising administering to the subject the peptide immunogen composition described herein. In some embodiments, provided herein are methods of inducing production of IgG (e.g., IgG1) antibodies but not IgM antibodies against a B cell epitope in a subject in need thereof, comprising administering to the subject the peptide immunogen composition described herein. In some embodiments, the methods and uses described herein comprise administering the peptide immunogen composition to the subject over a period of time of at least 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, or 15 years. In some embodiments, the methods and uses described herein comprise administering, or anticipated need for administering of, the peptide immunogen composition to the subject over a period of time of at least 3 years or 5 years. In some embodiments, the methods and uses described herein comprise administering, or anticipated need for administering of, the peptide immunogen composition to the subject over a period of time of at least 10 years or 15 years. In some embodiments, the methods described herein comprise administering the peptide immunogen composition at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 times to the subject. In some embodiments, the methods described herein comprise administering the peptide immunogen composition every 4 weeks to 6 months. In some embodiments, the methods described herein comprise administering the peptide immunogen composition every 47 ^ ^ Attorney Docket No. VXH-00225 ^ 8 weeks to 6 months. In some embodiments, the methods described herein comprise administering the peptide immunogen composition every month or 6 weeks. In some embodiments, the methods described herein comprise administering the peptide immunogen composition every 8 weeks or 2 months. In some embodiments, the methods described herein comprise administering the peptide immunogen composition every 3 months. In some embodiments, the methods described herein comprise administering the peptide immunogen composition every 4 months. In some embodiments, the methods described herein comprise administering the peptide immunogen composition every 5 months. In some embodiments, the methods described herein comprise administering the peptide immunogen composition every 6 months. In some embodiments, the methods described herein comprise administering the peptide immunogen composition from every 1 month to every 1 year. In some embodiments, provided herein are methods of treatment rather than prevention of a disease or condition, e.g., treatment of one or more symptoms of a disease or condition. In some embodiments, provided herein are methods of inhibiting of progression of a disease, condition, or a symptom thereof. In other embodiments, provided herein are methods of prevention of a disease or condition in a subject at risk of such disease or condition. In some embodiments, the prevention methods contemplated herein require or can benefit from long-term administration of a peptide immunogen composition described herein (e.g., administration more than 4, 5, 6, 7, 8, 9, 10, or 15 times over a period of at least 6 months, 1 year, 3 years, 5 years, 10 years, or more). In some embodiments, the methods provided herein include a priming regimen, wherein the peptide immunogen composition is administered to a subject in 1 to 3 doses (e.g., 1 dose, 2 doses, or 3 doses) within the first 4 to 12 weeks. In some embodiments, the methods provided herein include a priming regimen, wherein the peptide immunogen composition is administered to a subject in 1 to 3 doses (e.g., 1 dose, 2 doses, or 3 doses) within the first 4 to 8 weeks. In some embodiments, the priming regimen is administered at weeks 0, 3 and 6. In some embodiments, the methods provided herein further include a boosting regimen, wherein after the priming regimen, the peptide immunogen composition is continued to be administered, e.g., every 4 weeks, 8 weeks, 3 months, 4 months or 6 months, for at least 1 year, 2 years, 3 years or 5 years. In some embodiments, the methods provided herein further include a boosting regimen, wherein after the priming regimen, the peptide immunogen composition is continued to be administered every 2 months. In some embodiments, the methods provided herein further include a boosting regimen, wherein after the priming ^ ^ Attorney Docket No. VXH-00225 ^ regimen, the peptide immunogen composition is continued to be administered every 3 months. In some embodiments, any of the methods and uses described herein, do not lead to inflammation in a subject, i.e., the subject does not experience inflammation associated with the administration of the peptide immunogen composition (e.g., inflammation over the period of treatment). In some embodiments, any of the methods and uses described herein, do not lead to adverse inflammation in a subject, i.e., the subject does not experience adverse inflammation associated with the administration of the peptide immunogen composition (e.g., inflammation over the period of treatment). In any of the methods described herein, the subject can be a mammal. In preferred embodiments, the mammal is a human. However, any mammal, including domestic, farm, wild, or experimental animals can be treated in accordance with the described methods. Due to the advantages associated with the methods described herein, in some embodiments, the subject may not require concurrent or conjoint treatment with an anti- inflammatory drug. Accordingly, in some embodiments, the methods described herein do not comprise conjoint administration of an anti-inflammatory drug (e.g., to counteract inflammation associated with administration of the peptide immunogen composition). In some embodiments, the methods described herein do not comprise repeated conjoint administration of an anti-inflammatory drug. In some embodiments, the methods described herein do not comprise conjoint administration of an anti-inflammatory drug daily, twice a week, once a week, or once in two weeks (e.g., for at least 1 month, 2 months, 3 months, 4 months, 5 months or 6 months after administering the peptide immunogen composition). In some embodiments, the methods described herein do not comprise conjoint administration of a corticosteroid to the treated subject. In some embodiments, the methods described herein do not comprise conjoint administration of a nonsteroidal anti-inflammatory drug (NSAID) to the treated subject. In some embodiments, the methods described herein do not comprise conjoint administration of an antileukotriene and / or an immune selective anti-inflammatory derivative (ImSAID) to the treated subject. Patient Populations In some embodiments, the subject or a patient is a mammal. In some embodiments, the subject or a patient is a human. The human patients who can be treated according to the methods of the disclosure include pediatric, teen, adult, and elderly patients. Non-human animals, e.g., those described elsewhere herein, can also be treated according to the methods ^ ^ Attorney Docket No. VXH-00225 ^ of the disclosure. In some embodiments, the subject or a patient is non-human mammal. Non-human mammals include, without limitations, cattle, pigs, goats, sheep, horses, dogs, cats, and transgenic mammals. In some embodiments, the mammal is a farm animal (e.g., a cow, a pig, a goat, or a sheep). In some embodiments, the subject is a domestic animal (e.g., a dog or a cat).^In some embodiments, the mammal is a non-human primate. Subjects who can be treated according to the methods of the disclosure include patients, such as human patients, who have or are at risk of developing a disease or condition such as one or more disease or condition described herein. In some embodiments, the subject (e.g., a human) has or is at risk of developing a chronic disease or condition. In some embodiments, the subject (e.g., a human) has or is at risk of developing a neurodegenerative disease or condition. In some embodiments, the subject (e.g., a human) has or is at risk of developing an allergic disease or condition. In some embodiments, the subject (e.g., a human) has or is at risk of developing a inflammation or chronic inflammation. In some embodiments, the subject (e.g., a human) has or is at risk of developing an autoimmune disease or condition. In some embodiments, the administered dosages or effective amounts described herein depend on the age, weight, and general health of the subject in accordance with the knowledge of those skilled in the art. Kits In certain embodiments, also provided herein are kits comprising, essentially consisting of, or consisting of one or more peptide immunogens described herein, optionally one or more adjuvants described herein (in particular, one or more aluminum salts described herein), optionally a CpG oligonucleotide described herein, and optionally one or more excipients. In some embodiments, one or more adjuvants is aluminum phosphate. In some embodiments, one or more excipients do not comprise any adjuvants. In some embodiments, one or more excipients comprise only inactive components. In some embodiments, such kits comprise these components in separate containers. In some embodiments, the kits further comprise instructions for use, such as instructions regarding making a peptide immunogen composition using the provided components. In some embodiments, the kits further comprise a delivery vehicle (e.g., a syringe) for administering a peptide immunogen composition to a subject. ^ ^ Attorney Docket No. VXH-00225 ^ Numbered Embodiments 1. A peptide immunogen composition comprising a peptide immunogen comprising a heterologous Th epitope linked to a B cell epitope, wherein the B cell epitope does not ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ wherein the peptide immunogen composition (i) does not comprise an adjuvant or comprises a compatible adjuvant in an amount of up to about 1.6 mg / mL, wherein the compatible adjuvant is one or more aluminum salts, optionally wherein the one or more aluminum ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^.^^^^^^^^^^^^^0^^^C^^^^^^^^^1^^!^^^^^^^^^^0^ further comprises a polyanionic CpG oligonucleotide but does not comprise an adjuvant other than the compatible adjuvant. 2. The peptide immunogen composition of embodiment 1, wherein the one or more aluminum salts is aluminum phosphate. 3. The peptide immunogen composition of embodiment 1, wherein the one or more aluminum salts is aluminum hydroxide. 4. The peptide immunogen composition of any one of embodiments 1-3, wherein the compatible adjuvant is in an amount of about 0.8 mg / mL to about 1.6 mg / mL. 5. The peptide immunogen composition of embodiment 4, wherein the compatible adjuvant is in an amount of about 1.6 mg / mL. 6. The peptide immunogen composition of any one of embodiments 1-5, which comprises a polyanionic CpG oligonucleotide. 7. The peptide immunogen composition of embodiment 6, wherein the polyanionic CpG oligonucleotide is CpG1 or CpG3. 8. The peptide immunogen composition of embodiment 7, wherein CpG1 comprises SEQ ID NO:81 (5’ TCgTCgTTTTgTCgTTTTgTCgTTTTgTCgTT 3’), which is fully phosphorothioated. 9. The peptide immunogen composition of any one of embodiments 6-8, wherein the polyanionic CpG oligonucleotide is present in an amount up to about 200 µg / mL. 10. The peptide immunogen composition of embodiment 9, wherein the polyanionic CpG oligonucleotide is present in an amount of about 100 µg / mL to about 200 µg / mL. ^ ^ Attorney Docket No. VXH-00225 ^ 11. The peptide immunogen composition of embodiment 9, wherein the polyanionic CpG oligonucleotide is present in an amount of about 200 µg / mL. 12. The peptide immunogen composition of any one of embodiments 1-11, wherein the heterologous Th epitope is an artificial Th epitope. 13. The peptide immunogen composition of any one of embodiments 1-11, wherein the heterologous Th epitope is a promiscuous Th epitope. 14. The peptide immunogen composition of any one of embodiments 1-13, wherein the heterologous Th epitope comprises or has an amino acid sequence according to the formula ISIXEIXXVIVIVXXIEXILF (SEQ ID NO: 132), wherein X is any amino acid, optionally wherein the heterologous Th epitope comprises or has the amino acid sequence ISITEIKGVIVHRIETILF (SEQ ID NO: 32) or ISISEIKGVIVHKIETILF (SEQ ID NO: 30). 15. The peptide immunogen composition of embodiment 14, wherein the heterologous Th epitope has the amino acid sequence ISITEIKGVIVHRIETILF (SEQ ID NO: 32). 16. The peptide immunogen composition of any one of embodiments 1-15, wherein the B cell epitope does not comprise a Th epitope. 17. The peptide immunogen composition of any one of embodiments 1-16, wherein the peptide immunogen does not comprise an endogenous Th epitope or does not comprise a naturally occurring Th epitope. 18. The peptide immunogen composition of any one of embodiments 1-17, wherein the peptide immunogen does not comprise a Th epitope naturally occurring in a pathogen protein, wherein the pathogen protein is Measles Virus Fusion (MVF) protein, Hepatitis B Surface Antigen (HBsAg), influenza protein, Clostridium tetani protein, Bordetella protein, Diphtheria protein, Plamsodium falciparum protein, Schistosoma mansoni protein, MCMV protein, or Epstein-Barr virus (EBV) protein. 19. The peptide immunogen composition of any one of embodiments 1-18, wherein the B cell epitope is a peptide from a protein associated with or involved in pathogenesis of a disease or condition. 20. The peptide immunogen composition of embodiment 19, wherein the disease or condition is a chronic disease or condition, neurodegenerative disease or condition, allergic disease or condition, or a cancer. ^ ^ Attorney Docket No. VXH-00225 ^ 21. The peptide immunogen composition of embodiment 19, wherein the disease or condition is tauopathy, Alzheimer’s, synucleinopathy, Parkinson’s, dementia with Lewy bodies (DLB), multiple system atrophy (MSA), migraine, hypercholesterolemia, hyperlipidemia, or atopic dermatitis. 22. The peptide immunogen composition of any one of embodiments 1-21, wherein the B cell epitope is 7 to 50 amino acids in length. 23. The peptide immunogen composition of any one of embodiments 1-22, wherein the B cell epitope is a peptide from alpha-synuclein protein, Tau protein, ^ amyloid protein, calcitonin gene-related peptide (CGRP), proprotein convertase subtilisin / kexin type 9 (PCSK9), interleukin-31, or membrane-bound IgE^^^^^^^^^^^^^^^^^^^^^^0^^^^^^^8^^^^^^^^^^^ of said B cell epitope. 24. The peptide immunogen composition of any one of embodiments 1-23, wherein the B cell epitope is or comprises the amino acid sequence of EMPSEEGYQD (SEQ ID NO: 8), VPTNVGSKAF (SEQ ID NO: 51), SIPWNLERIT (SEQ ID NO: 55), DAEFRHDSGYEVHH (SEQ ID NO: 1), IKHVPGGGSVQIVYK (SEQ ID NO: 13), or DHAGTYGLGD (SEQ ID NO: 15). 25. The peptide immunogen composition of any one of embodiments 1-24, wherein the promiscuous Th epitope is covalently linked to a B cell epitope with a heterologous linker comprising a naturally occurring amino acid and / or a non-naturally occurring amino acid. 26. The peptide immunogen composition of embodiment 25, wherein the heterologous linker comprises one or more amino acid lysine, optionally wherein the heterologous linker comprises three or four lysines, optionally wherein the linker is ^K-KKK (SEQ ID NO: 130) or KKK-^K (SEQ ID NO: 129)^ 27. The peptide immunogen composition of any one of embodiments 1-26, wherein the peptide immunogen comprises one of the following formulae: (Th)m-(A)n-(B)-X or (B)-(A)n-(Th)m-X, wherein: Th is the heterologous ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ 4^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^ ^ Attorney Docket No. VXH-00225 ^ B is the B cell epitope, optionally wherein the B cell epitope comprises 6 to 50 amino acid ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ X is an -COOH or -CONH2 of an amino acid (indicating that the C-terminal amino acid may be amidated, i.e., the peptide immunogen may have an amide group at the C-terminal end). 28. The peptide immunogen composition of embodiment 27, wherein n is 1 to 4. 29. The peptide immunogen composition of embodiment 27 or 28, wherein m is 1. 30. The peptide immunogen composition of any one of embodiments 1-29, wherein the peptide immunogen does not comprise any other epitope, peptide or protein sequence. 31. The peptide immunogen composition of any one of embodiments 1-30, wherein the peptide immunogen comprises the amino acid sequence ISITEIKGVIVHRIETILF-^k-kkk- EMPSEEGYQD (SEQ ID NO: 92), ISITEIKGVIVHRIETILF-^k-kkk-VPTNVGSKAF (SEQ ID NO: 107), SIPWNLERIT-KKK-^K-ISITEIKGVIVHRIETILF (SEQ ID NO: 113), DAEFRHDSGYEVHH-^K-KKK-ISITEIKGVIVHRIETILF (SEQ ID NO: 88), ISITEIKGVIVHRIETILF-^K-KKK-IKHVPGGGSVQIVYK (SEQ ID NO: 98), or DHAGTYGLGD-KKK-^K-ISITEIKGVIVHRIETILF (SEQ ID NO: 100). 32. The peptide immunogen composition of any one of embodiments 1-31, wherein the peptide immunogen is not or does not comprise the amino acid sequence ISITEIKGVIVHRIETILF-^k-kkk-EMPSEEGYQD (SEQ ID NO: 92), or the B cell epitope is not or does not comprise the amino acid sequence EMPSEEGYQD (SEQ ID NO: 8). 33. The peptide immunogen composition of any one of embodiments 1-32, which comprises the peptide immunogen in an amount from about 10 to 2000 µg / mL. 34. The peptide immunogen composition of embodiment 33, which comprises the peptide immunogen in an amount from about 10 to about 1000 µg / mL. 35. The peptide immunogen composition of embodiment 34, which comprises the peptide immunogen in an amount from about 10 to 500 µg / mL. 36. The peptide immunogen composition of embodiment 35, which comprises the peptide immunogen in an amount from about 100 to 250 µg / mL. 37. The peptide immunogen composition of any one of embodiments 1-36, which when administered to a mammal induces production of IgG1 isotype antibodies to the B cell ^ ^ Attorney Docket No. VXH-00225 ^ epitope, optionally wherein IgG1 antibody production is assessed from about week 1 to about week 12 after administration. 38. The peptide immunogen composition of any one of embodiments 1-37, which when administered to a mammal induces substantially higher production of IgG antibodies than IgM antibodies to the B cell epitope, optionally wherein antibody production is assessed from about week 1 to about week 12 after administration, optionally wherein substantially higher is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher. 39. The peptide immunogen composition of embodiment 38, wherein the IgG antibodies are of IgG1 isotype. 40. The peptide immunogen composition of any one of embodiments 1-39, which when administered to a mammal substantially does not induce production, or induces no detectable production, of IgM antibodies, optionally wherein IgM antibody production is assessed from about week 1 to about week 12 after administration. 41. The peptide immunogen composition of any one of embodiments 1-40, which when administered to a mammal induces substantially higher production of IgG1 isotype antibodies than IgG2, IgG3 and / or IgG4 isotype antibodies to the B cell epitope, optionally wherein antibody production is assessed from about week 1 to about week 12 after administration, optionally wherein substantially higher is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher. 42. The peptide immunogen composition of any one of embodiments 1-41, which when administered to a mammal substantially does not induce production, or induces no detectable production, of IgG2, IgG3 and / or IgG4 isotype antibodies, optionally wherein antibody production is assessed from about week 1 to about week 12 after administration. 43. The peptide immunogen composition of any one of embodiments 1-42, which when administered to a mammal substantially does not induce, or induces no detectable, innate immunity or T cell inflammation, optionally wherein the innate immunity or T cell inflammation is assessed from about week 1 to about week 12 after administration. 44. The peptide immunogen composition of any one of embodiments 37-43, wherein the mammal is a human or a non-human primate. ^ ^ Attorney Docket No. VXH-00225 ^ 45. A method of inducing production of IgG1 antibodies but not IgM antibodies against a B cell epitope in a subject in need thereof, comprising administering (such as parenterally, e.g., intramuscularly or intradermally) to the subject the peptide immunogen composition of any one of embodiments 1-44. 46. A method of inducing production of antibodies against a B cell epitope in a subject suffering from, or at risk of, a disease or condition associated with, or caused by, a target antigen comprising the B cell epitope, optionally wherein the disease or condition is a chronic disease or condition, an autoimmune disease or condition, a chronic inflammation, a neurodegenerative disease or condition, a cancer, or an allergic disease or condition, comprising administering (such as parenterally, e.g., intramuscularly or intradermally) to the subject the peptide immunogen composition of any one of embodiments 1-44. 47. A method of treating or preventing a disease or condition associated with, or caused by, a target antigen comprising the B cell epitope, comprising administering (such as parenterally, e.g., intramuscularly or intradermally) to the subject the peptide immunogen composition of any one of embodiments 1-44, optionally wherein the disease or condition is a chronic disease or condition, an autoimmune disease or condition, a chronic inflammation, a neurodegenerative disease or condition, a cancer, or an allergic disease or condition. 48. The method of any one of embodiments 44-47, which comprises administering the peptide immunogen composition to the subject over a period of time of at least 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, or 15 years. 49. A method of inducing long-term production of antibodies against a B cell epitope, or preventing or treating a disease or condition associated with a target antigen comprising the B cell epitope, in a subject in need thereof, comprising administering (such as parenterally, e.g., intramuscularly or intradermally) a peptide immunogen composition to a subject over a period of time of at least 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, or 15 years, wherein the peptide immunogen composition comprises a heterologous Th epitope linked to a B cell epitope, optionally wherein the B cell epitope does not comprise an endogenous Th epitope^ wherein the peptide immunogen composition does not comprise an adjuvant or comprises a compatible adjuvant in an amount up to about 1.6 mg / mL, wherein the compatible adjuvant is one or more aluminum salts, optionally wherein the one or more aluminum salts is aluminum phosphate and / or aluminum hydroxide. ^ ^ Attorney Docket No. VXH-00225 ^ 50. The method of embodiment 49, wherein the disease or condition is a chronic disease or condition, a neurodegenerative disease or condition, or an allergic disease or condition. 51. The method of embodiment 49 or 50, wherein the peptide immunogen composition further comprises a polyanionic CpG oligonucleotide but does not comprise another adjuvant. 52. The method of any one of embodiments 49-51, wherein the peptide immunogen composition is the peptide immunogen composition of any one of claims 1-44. 53. The method of any one of embodiments 48-52, wherein administering comprises administering at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 times to the subject. 54. The method of any one of embodiments 48-53, wherein administering comprises administering every 8 weeks to 6 months. 55. The method of any one of embodiments 48-54, wherein administering comprises administering a priming regimen of 1 to 3 doses within about 4-12 weeks, followed by administering of a booster dose every 4 weeks to 6 months. 56. The method of embodiment 55, wherein the priming regimen comprises 2 or 3 doses, optionally wherein the priming regimen is administered at weeks 0, 3 and 6. 57. The method of any one of embodiments 45-56, wherein the subject does not experience adverse inflammation associated with the administration of the peptide immunogen composition. 58. The method of any one of embodiments 45-57, which does not comprise conjoint administration of an anti-inflammatory drug to counteract inflammation associated with administration of the peptide immunogen composition. 59. The method of any one of embodiments 45-58, which does not comprise administration of an anti-inflammatory drug conjointly with the peptide immunogen composition (such as wherein the lack of inflammation due to administration of a peptide immunogen allows to forego administration of anti-inflammatory drugs in conjunction with the therapy described herein). 60. The method of embodiment 59, which does not comprise administration of an anti- inflammatory drug at least daily, twice a week, once a week, or once in two weeks for at least ^ ^ Attorney Docket No. VXH-00225 ^ 1 month, 2 months, 3 months, 4 months, 5 months or 6 months after administering the peptide immunogen composition. 61. The method of any one of embodiments 58-60, wherein the anti-inflammatory drug is a corticosteroid, a nonsteroidal anti-inflammatory drug (NSAID), an antileukotriene, and / or an immune selective anti-inflammatory derivative (ImSAID). 62. The method of any one of embodiments 45-61, wherein the subject is a human. 63. The method of any one of embodiments 45-62, wherein administering the peptide immunogen composition induces production of IgG1 isotype antibodies to the B cell epitope in the subject, optionally wherein IgG1 antibody production is assessed from about week 1 to about week 16 after administration. 64. The method of any one of embodiments 45-63, wherein administering the peptide immunogen composition induces substantially higher production of IgG antibodies than IgM antibodies to the B cell epitope in the subject, optionally wherein antibody production is assessed from about week 1 to about week 16 after the administering, optionally wherein substantially higher is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher. 65. The method of embodiment 64, wherein the IgG antibodies are of IgG1 isotype. 66. The method of any one of embodiments 45-65, wherein administering the peptide immunogen composition substantially does not induce production, or induces no detectable production, of IgM antibodies in the subject, optionally wherein IgM antibody production is assessed from about week 1 to about week 16 after administration. 67. The method of any one of embodiments 45-66, wherein administering the peptide immunogen composition induces substantially higher production of IgG1 isotype antibodies than IgG2, IgG3 and / or IgG4 isotype antibodies to the B cell epitope in the subject, optionally wherein antibody production is assessed from about week 1 to about week 16 after administration, optionally wherein substantially higher is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher. 68. The method of any one of embodiments 45-67, wherein administering the peptide immunogen composition substantially does not induce production, or induces no detectable production, of IgG2, IgG3 and / or IgG4 isotype antibodies in the subject, optionally wherein antibody production is assessed from about week 1 to about week 16 after administration. ^ ^ Attorney Docket No. VXH-00225 ^ 69. The method of any one of embodiments 45-68, wherein administering the peptide immunogen composition substantially does not induce, or induces no detectable, innate immunity or T cell inflammation in the subject, optionally wherein the innate immunity or T cell inflammation is assessed from about week 1 to about week 16 after administration. 70. A peptide immunogen composition comprising: a peptide immunogen comprising: (a) a target antigenic site (such as any target antigenic site or B cell epitope described herein, e.g., as set forth in Table 1), (b) means for evocation of a T helper cell response (such as any described herein), and (c) means for covalent linkage between (a) and (b) (such as any described herein)^ wherein the peptide immunogen composition (i) does not comprise an adjuvant or comprises a compatible adjuvant in an amount of up to about 1.6 mg / mL, wherein the compatible adjuvant is one or more aluminum salts, optionally wherein the one or more aluminum ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^.^^^^^^^^^^^^^0^^^C^^^^^^^^^1^^!^^^^^^^^^^0^ further comprises a polyanionic CpG oligonucleotide but does not comprise an adjuvant other than the compatible adjuvant. 71. The peptide immunogen composition of embodiments 1-44 or 70, wherein the peptide immunogen is any one of the peptide immunogens described herein, e.g., as set forth in Table 4. 72. Any use of embodiment 70 or 71, or method of producing antibodies, prevention or treatment of disease or condition using embodiment 70 or 71, which is described herein, e.g., any method set forth in the numbered embodiments or claims that follow. TABLES Table 1: Examples of target antigenic sites (B cell epitopes) ^ ^ Attorney Docket No. VXH-00225 ^ ^ ^ Attorney Docket No. VXH-00225 ^ * B cell epitope peptides are cyclized by cysteine disulfide bonds, e.g., as shown with certain cysteines underlined. The cysteines / serines that substitute the amino acids of the PCSK9 fragments are in italics.^ Table 2: Amino Acid Sequences of Pathogen Protein Derived Th Epitopes Including Idealized Artificial Th Epitopes for Use in Peptide Immunogens Described Herein ^ ^ Attorney Docket No. VXH-00225 ^ Table 3: Exemplary CpG Oligonucleotides Table 4: Exemplary peptide immunogen constructs ^ ^ Attorney Docket No. VXH-00225 ^ ^ ^ Attorney Docket No. VXH-00225 ^ ^ ^ Attorney Docket No. VXH-00225 ^ * Peptides are cyclized by cysteine disulfide bonds, e.g., as shown with the cysteines underlined. The Cysteines / Serines that substitute the amino acids of the PCSK9 fragments are in italics.^ The compositions, methods, and examples provided herein are illustrative only and not intended to be limiting.^ EXAMPLES The present Examples demonstrate that peptide immunogen compositions as set forth in the present disclosure can elicit a specific humoral immune response to target antigenic sites. The present examples provide data showing that exemplary peptide immunogen compositions can effectively enhance desired immunogenicity and minimize inflammation and / or non-specific immunogenicity by specifically inducing IgG1 antibodies against PCSK9 and CGRP targets with no or substantially no induction of IgM antibody production or inflammation. Example 1: Aluminum salt (Alum)-based peptide immunogen composition induced specific and potent anti-CGRP immune response, including anti-CGRP IgG1 antibody titers with no or low IgM antibody and inflammatory responses. Immunogenicity A polyanionic CpG oligonucleotide (ODN, CpG1) was formulated with peptide immunogens comprising Th-hCGRP28-37or Th-rCGRP28-37(see Table 5), at a 1.8:1 (peptide:CpG1) molar charge ratio. The peptide / CpG1 complexes were further formulated with either alum adjuvant (Adju-Phos®) or oil-in-water emission adjuvant (Montanide™ ISA 51VG). Adju-Phos®vaccine formulations contained 1500 "g / ml of peptide(s), 445 "g / ml of CpG1 (peptide:CpG1 molar charge ratio as 1.8:1) and 1.6 mg / ml of Aluminum. The ISA 51VG vaccine formulations contained 1500 "g / ml of peptide(s), 445 "g / ml of CpG1 (peptide:CpG1 molar charge ratio as 1.8:1). Vaccine formulation with p4796kb was injected IM into Guinea pigs at 40 ug peptide in CpG1 + ADJU-PHOS® at weeks 0, 3 and 6, into rats at 30 ug peptide in CpG1 + ADJU- PHOS® at weeks 0, 3, 6 and 9, into Cynomolgus macaques at 300 ug peptide in CpG1 + ADJU-PHOS® at weeks 0, 3 and 6. Serum samples were obtained every 3 weeks and used in ELISA-based titer assays to evaluate the antibody response against human or rat CGRP. OD ^ ^ Attorney Docket No. VXH-00225 ^ 450 readings were obtained and a non-linear four-parameter curve fit was applied to each dilution curve to calculate the EC50 (SoftMax Pro, Molecular Devices, PA). Results in Figure 1 demonstrate that the vaccine formulation with p4796kb was highly immunogenic across species (rats, guinea pigs, and nonhuman primates) with high titers of antibodies maintained over time. Table 5: Amino Acid Sequences of CGRP Peptide Immunogen Constructs The CGRP sequence targeted by p4796kb shares perfect sequence homology to rat ^CGRP. To generated vaccine derived antibodies targeting CGRP in rats, an additional peptide immunogen, p5830kb, that contains a single amino acid substitution (K35E) was produced. IgG1 Induction by Immunization Construct p4796kb at 300 ug peptide formulated in CpG1 and either ADJU-PHOS® or ISA 51VG as described above was injected IM into rats on days 0, 21, 42, 56, and 84. Serum samples were collected on days 14, 35, 58, 79, and 105 to evaluate the antibody responses. A Cynomolgus macaque study was conducted to further evaluate the immunogenicity of p4796kb in the ADJU-PHOS® / CpG1 formulation. Macaques were IM injected at 300 ug peptide in CpG1 + ADJU-PHOS®^at weeks 0, 3, 6, 9, and 12. Serum samples were collected prior to each dose and 3 weeks after the last immunization to evaluate the CGRP-specific antibody responses. For antibody characterization, sera were passed through a 0.2 "m filter. To isolate total IgG fractions, NAb A / G protein columns (Thermo Fisher Scientific) were washed with two resin volumes of Pierce Protein A / G Binding Buffer (Thermo Fisher Scientific). After filtration, sera were diluted two-fold in binding buffer and incubated with end-over-end mixing for one hour. The column was subsequently washed with two volumes of binding buffer and bound antibodies are eluted four times in 5 mL of IgG Elution Buffer (GBiosciences) neutralized with 250 "L of Tris-HCl (pH 8.0, Anatrace). Triplicate IgG isolations were performed for each group. Total IgG fraction was concentrated to E 2% of its original volume in a 100 kDa Amicon filter unit (MilliPoreSigma) with centrifugation at 6°C ^ ^ Attorney Docket No. VXH-00225 ^ and 4000 x g, then buffer exchanged into ultrapure DNase / RNase free distilled water (Invitrogen). The protein content of the total IgG fraction concentrate was determined using a QuBit Fluorometer 4.0 (Invitrogen) protein assay, per the manufacturer’s instructions. In rats, peptides formulated in ADJU-PHOS® induced robust anti-CGRP IgG antibody titers with limited production of IgM against CGRP (Figures 2A, 2B). In contrast, peptides formulated in ISA-51VG induced both IgG and IgM antibody titers (Figures 2A, 2B), indicating a much stronger innate immune response when using this adjuvant. Further assessments of the IgG isotypes produced after immunization with an Alum-based formulation indicated a predominant production of IgG1 (Figure 3A). Indeed, the IgG1 geometric mean EC50 titer (GMT-EC50) was 1:122,180 and was 308.3-fold higher than IgG2a (GMT-EC501:308), 8.4- fold higher than IgG2b (GMT-EC501:14,622) and 57.7-fold higher than IgG2c (GMT-EC50 1:2118). However, using the same peptide immunogen formulated in ISA-51VG, the isotypes were more balanced than when using ADJU-PHOS® (Figure 3B). In macaques, immunization with p4796kb formulated in ADJU-PHOS® induced high titers of anti-CGRP IgG1, with no detectable CGRP-specific IgG2, IgG3 and IgG4 antibodies (Figure 3C). Altogether these data confirm that the full peptide immunogens formulated in ADJU-PHOS® induces potent antibody responses enriched for IgG1 without apparent engagement of the innate system (i.e., low induction of IgM antibodies). Peptide Immunogens Do Not Induce T Cell Activation or Long-term Autoimmunity Immune responses, including IFNgamma and IL-4 secretion, to peptide components of the vaccine was evaluated using enzyme linked immunosorbent spot (ELISpot) assays.^ Splenocytes were collected from vaccine-naïve rats and from immunized rats 3 weeks after the 5th injection. Splenocytes were stimulated in vitro with each individual peptide component of the vaccine: Th peptides, CGRP28-37 or full peptide immunogen. Each peptide was tested at 5 "g / mL. Control splenocytes were stimulated either with medium alone (negative control) or 1 "g / mL ConA (positive control). The rat ELISpot assays were performed using the Rat IFN; ELISpotPLUS kit (MABTECH, Nacka Strand, Sweden) and Rat IL-4 ELISpot kit (UCyTech, Utrecht, Netherlands). ELISpot plates precoated with a capture antibody were blocked with lymphocyte culture medium for at least 30 min at RT. For IFN; detection, rat splenocytes at 100,000 cells / well were plated into each well and stimulated with individual peptide for 48 hour at 37°C. The IFN; secreting cells were detected using a biotinylated anti-IFN; antibody. For IL-4, rat splenocytes at 400,000 cells / well were plated into each well and stimulated with individual peptide for 72 hours at ^ ^ Attorney Docket No. VXH-00225 ^ 37°C. The IL-4 secreting cells were detected using a biotinylated anti-IL-4 antibody. This was followed by incubation with HRP-conjugated Strepavidine. Cytokine detection and spot developing procedures were performed based on the manufacturer’s instructions. Spots were scanned and quantified using an AID iSpot reader (Advanced Imaging Devices GmbH, Germany). Spot-forming units (SFU) per million cells was calculated by subtracting the negative control wells. Vaccine-naïve splenocytes (from the adjuvant-treated group) did not respond to stimulation with any of the peptide components of the immunogen, strongly suggesting that T cells do not naturally react to these peptides. In contrast, both the Th peptide and the full peptide immunogen induced the secretion of IFNgamma (Figure 4) and IL-4 in splenocytes collected after immunization, suggesting T cell activation. Importantly, immune cells do not react to the endogenous CGRP epitope, even after immunization, indicating that maintenance of antibody production will require re-exposure to the peptide immunogen. Chronic inflammation from immunization was assessed. A panel of 9 inflammatory cytokines (IFN;, IL-1^, IL-4, IL-5, IL-6, IL-10, IL-13, KC / Gro and TNF- ) were measured in rat serum samples collected before immunization and 6 hours after each immunization. For each peptide vaccine (p4796kb or p5830kb), vaccinated rats showed cytokines levels within the range observed in adjuvant-treated rats (see Table 6). Consistent results were observed in a separate rat GLP toxicity study where cytokines were assessed 24 hours after each injection (6 bi-weekly injections). Sporadic and minimal increases of IL-1^, IFN; and TNF- serum concentrations were observed following p4796kb injections in some male rats, but changes returned to normal values rapidly. This GLP toxicity study concluded that vaccination was safe and tolerated in rats, with no signs of chronic inflammation. Table 6: Summary of cytokines profiling data. Ranges from each group denote the low to high cytokine concentrations (in pg / mL) at any time point during the course of the study. ^ ^ Attorney Docket No. VXH-00225 ^ Vaccine Derived Antibodies are Comparable to mAbs Targeting CGRP To confirm that the antibodies produced after immunization had the desired properties, binding potencies and affinities of the antibodies were characterized. Human CGRP specific IgG was affinity-purified from immunized guinea pig sera and compared to a mAb (Galcanezumab) for their binding kinetics by Surface Plasmon Resonance (SPR) using a direct immobilization of antibodies at 25°C on a CM5 sensor chip using Biacore 8K. The KD (equilibrium dissociation constant, Kd (dissociation rate) / Ka (association rate)) was calculated using the Biacore 8K analysis software (BIAevaluation). The affinities were determined by using single cycle kinetics analysis. Galcanezumab and affinity purified antibodies had calculated equilibrium dissociation constants (KD) of 10.7 pM and 13.1 pM, respectively, with similar association (1.01 x 106 1 / Ms vs.3.50 x 1061 / Ms) and dissociation rates (1.08 x 10-51 / s vs 4.57 x 10-51 / s). Moreover, the affinity purified antibodies from p4796kb-immunized guinea pigs bound to human CGRP with comparable potency as Galcanezumab in an ELISA binding assay (Figure 5A). These experiments demonstrated that IgG produced after immunization with p4796kb bind to human CGRP with affinity and potency in the range of a therapeutic mAb. Additionally, whether anti-CGRP antibodies could block the activity of CGRP to the same extent as Galcanezumab was determined in SK-N-MC cells using the Bridge-It® Cyclic AMP assay. Pre-treatment of the cell cultures with varying concentrations of anti-CGRP antibodies demonstrated a dose-dependent reduction of CGRP-induced cAMP (Figure 5B). Affinity purified IgG derived from p4796kb immunization showed a similar in vitro activity (EC50 = 2.187x10-8M) to Galcanezumab (EC50 = 2.438x10-8M) while the total IgG fraction purified from pre-immune Guinea pig sera did not have detectable activities at all concentrations tested. These results indicate that CGRP-specific IgG induced by immunization inhibit CGRP signaling, comparable to a therapeutic anti-CGRP mAb. ^ ^ Attorney Docket No. VXH-00225 ^ In addition, the functional effects of immunization were assessed in a pharmacodynamic rat model, the capsaicin-induced increase in dermal blood flow (DBF). Rats received repeat intramuscular injections of saline, Adju-Phos®, adjuvanted p4796kb vaccine, or adjuvanted p5830kb vaccine at 300 "g on Days 1, 22, 43, 64, and 85. An additional group of rats received a single intravenous infusion of Galcanezumab at 5 mg / kg on Day 85. The capsaicin challenge was conducted 2 weeks after the 5th immunization or after Galcanezumab injection. Antibody titers against human CGRP and rat CGRP were also evaluated during the course of the study. In this study, rats receiving p4796kb again developed antibody titers ~100 times lower against rat CGRP than against human CGRP. In contrast, rats receiving p5830kb (anti-rat CGRP vaccine) developed similar antibody titers against both human and rat CGRP. As expected, capsaicin induced a significant increase in dermal blood flow in rats immunized with saline or Adju-Phos, an effect that was significantly blocked by Galcanezumab (p < 0.0001). There was no significant effect of p4796kb immunization on dermal blood flow as compared to the saline and Adju-Phos groups. However, immunization with p5830kb significantly reduced the response to capsaicin (p < 0.001) compared to the saline and Adju-Phos groups. Furthermore, there was no significant difference in the response to capsaicin between Galcanezumab-treated and p5830kb-immunized groups. These results strongly suggest that the lack of efficacy of p4796kb in the rat capsaicin challenge model is due to the antibody specificity and poor antibody binding to rat aCGRP. In contrast, rats immunized with p5830kb generated high antibody titers against rat aCGRP, which resulted in significant effects in the rat capsaicin challenge model. Example 2: Aluminum salt (Alum)-based peptide immunogen composition induced specific and potent anti-PCSK9 immune response, including anti-PCSK9 IgG1 antibody titers with no or low IgM antibody and inflammatory responses. Immunogenicity Peptide immunogen vaccine VXX-401 has PCSK9 peptide immunogen (p5494kb), 200 "g / ml of CpG1, and 1.6 mg / ml of ADJU-PHOS®. PCSK9 peptide immunogen p5494kb has the amino acid sequence SIPWNLERIT-KKK-^K-ISITEIKGVIVHRIETILF (SEQ ID NO: 113). The immunogenicity and in vivo efficacy of peptide immunogen p5494kb was evaluated in non-human primates (NHP), i.e., cynomolgus monkeys, which show strong homology with human PCSK9 and also show similar lipid metabolism compared to humans. ^ ^ Attorney Docket No. VXH-00225 ^ Monkeys received priming regimen of p5494kb formulated in Adju-Phos (0.8 mg / dose) and CpG3 (50 "g / dose), followed by a boosting regimen of p5494kb formulated in ISA51 VG (50% / dose) and CpG3 (50 "g / dose). Monkeys were randomized across study groups based on pre-dose serum levels of LDL-C. Each animal received a total of six IM injections (0.5 mL / dose) of 300 "g / dose p5494kb or adjuvant placebo. The priming regimen consisted of a 300 "g p5494kb given IM on weeks 0, 3, and 6. The boosting regimen consisted of a 300 "g p5494kb given IM on weeks 13, 16, and 19. A separate group of cynomolgus monkeys received IM injections of saline during on weeks 0, 3, 6, 13 and 16, and received a single IV bolus of evolocumab (3 mg / kg, Amgen) on week 19. Animals were followed through week 25, with blood samples collected every week until completion. p5494kb induced serum anti-PCSK9 antibodies with peak titers of log10EC50 of 3.75 by week 9. Titers thereafter decreased by one order of magnitude by week 13. A single boost of 300 ug p5494kb on week 13 restored antibody levels to log10EC504.18 by week 16. Peak titers (log10EC50 of 4.47) were achieved after the 3-dose boosting regimen by week 22 (Figure 6A). As expected, no PCSK9-specific antibodies were detected in the sera from the adjuvant control group. Serum concentrations of LDL-C and HDL-C were quantified in two- week intervals and the average was normalized to the pre-dose baseline. Serum LDL-C in the p5494kb treatment group progressively decreased over the course of the initial priming regimen, reaching a 35% reduction by week 13. After boosting, LDL-C further decreased to 43% of baseline, and this reduction was maintained through week 25 (Figure 6B). At week 19, an IV injection of evolocumab was administered (3 mg / kg) to an additional group of monkeys that had previously received only saline injections. The bolus of monoclonal antibody reduced serum LDL-C by a 3-week average of 45%, an extent which was statistically indistinguishable from that of the p5494kb treatment group. However, serum LDL-C was restored to baseline within two weeks of dosing with the monoclonal antibody (Figure 6B). None of the treatments were found to alter levels of serum HDL-C. Dose-dependent effects of VXX-401 on immunogenicity and serum LDL-C over a 48-week period were evaluated in cynomolgus monkeys. Monkeys were randomly assigned to seven groups and received IM injections (0.5 mL / dose) of placebo or VXX-401 (10, 30, 100, 300, and 900 "g / dose) on weeks 0, 3, and 6 as the priming regimen. At week 24, all animals received a placebo or booster dose of VXX-401 (100 "g / dose). Injection sites were ^^^^^^^^^^^^^%^^%^^^^^^^^(^^^^^^^^^^^^^^^^^^^^^^^0^?^^^^^^?^^^^^^^^^^^^^^^^^^^^^^^^^^^^se ^^^^^8^^0^^?^^?^^^^^^^^^^^^^^^^^^^^^^^^0^^^^^^^^^^^^^?^^^^^^^^^^^^^^^-dose and 24 h after each injection. Blood samples were collected to evaluate clinical chemistry, including LDL- ^ ^ Attorney Docket No. VXH-00225 ^ C, HDL-C, and total cholesterol (pre-^^^^^^^^^?^^^^0!^^^^^^^^^^^0^1^^^-dose, day 42, and ^^0^^^(!^^^0^^^^^^^^1^^^^^^^^-^^^^^^^^^^^^0^^^^^%^^^^^^^^%!^^^^^^^^^^^^^^^^-PCSK9 titers (pre-dose and days 0, 21, 42, 63, 84, 105, 126, 147,168, and 189). Anti-PCSK9 antibodies were detectable in serum within three weeks of the initial dose. At the 3-week timepoint, the highest titers (log10EC503.40) were observed in the monkeys dosed with 100 "g of VXX-401 (Figure 6C). Overall, peak titers were achieved by week 6 to 9 and were comparable between the different dosage groups (i.e., log10EC503.21 to 3.67). Antibody levels in all VXX-401 treatment groups exhibited a gradual decline beginning at week 12, with titers deteriorating to near baseline levels by week 24 (Figure 7A). A boosting dose of 100 ug on week 24 restored maximal titers. In this study, LDL-C and HDL-C levels were quantified in three-week intervals and the average was normalized to the pre-dose level. The most pronounced LDL-C reduction was observed in the animals that received 100 "g per dose of VXX-401, which was decreased from baseline by 24% at week 9 (Figure 6D). Animals who received 10 "g or 30 "g per dose of VXX-401 showed average LDL-C reductions between 10 and 15% from baseline. Finally, the monkeys given 300 "g or 900 ug of VXX-401 exhibited negligible reductions in LDL-C (< 10%) compared to pre-dose levels (Figure 7B). The more pronounced effects of 100 ug VXX-401 on serum LDL-C might be due to the more rapid antibody response observed in this group, supporting the notion that a rapid antibody response might be necessary to overcome target-mediated clearance. Serum LDL-C returned to pre-dose levels by week 24 in all groups, which coincided with the return of anti-PCSK9 titers to baseline. As expected, the single boost of 100 ug VXX-401 on week 24 reduced serum LDL-C by roughly 35% from the baseline taken right before the boost 1F^^^^^^^B^^F^^^^^^&3!#^*^^^^^GBH-C was not altered by treatment in any groups. Safety and tolerability of VXX-401 were evaluated under Good Laboratory Practices (GLP)-conditions in cynomolgus monkeys. Monkeys^were randomized to receive either saline placebo, adjuvant control (0.8 mg Adju-Phos and 100 "g CpG1), a low dose of VXX- 401 (100 "g peptide / dose), or a high dose of VXX-401 (600 "g peptide / dose) administered IM (0.5 mL / dose) for five total injections on days 1, 22, 43, 64, and 85. Terminal necropsy was performed at day 88. Animals were between 2 and 4 years old and weighed between 2.7 to 4.4 kg for males (n = 19, 4 to 5 per group) or 2.3 to 5.2 kg for females (n = 18, 4 to 5 per group) at the first dose. Clinical observations made over the course of the study included ^^^^^^^^0.^^^^^^^^^^0^^^^0^^^^^^^C^^^^^^^^^^^^^^^0^?^^^^^^^^^^0^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^8^^^^^^^^^^^^^^I^^^^^^^^^^^^^^^^ reactogenicity. Safety pharmacology assessments for the cardiovascular, respiratory, and central nervous system were also 72 ^ ^ Attorney Docket No. VXH-00225 ^ included. In addition, blood and urine samples were collected for clinical pathology evaluations including hematology, coagulation, clinical chemistry (i.e., LDL, HDL, total cholesterol, and triglycerides), and urinalysis. Serum samples were obtained for evaluation of anti-PCSK9 antibody titers and cytokines. Lastly, a complete necropsy was performed for all animals, including a standard panel of tissues collected for histopathological evaluation. Serum anti-PCSK9 antibody levels increased substantially between the initial priming dose and week 6, reaching a peak of log10EC503.14 in the 100 ug dose group (Figure 6E). Antibody titers remained high and stable (i.e., log10EC50 of 3) from week 6 until the end of the study. No clear dose-dependency was observed between the 100 and 600 ug per dose VXX-401 treatment groups (Figure 7D). Additionally, no PCSK9-specific antibodies were detected in the adjuvant control nor the PBS placebo groups. VXX-401 treatment induced a sustained decrease in serum LDL cholesterol, achieving up to 31% reduction from baseline (Figures 6F, 7E). These changes are consistent with the expected pharmacological effects of VXX-401 and no notable changes in HDL were observed. VXX-401 Induces Potent Anti-PCSK9 Antibodies Antibody potency was evaluated similarly as in Example 1. Affinity purified antibodies isolated from the sera of VXX-401 immunized NHP demonstrated potent binding to human PCSK9 via ELISA, with an EC500.621 "g / ml that was comparable to evolocumab at 0.547 "g / ml (Figure 84^^Table 7). Additionally, these antibodies had a protective effect on the uptake of pHrodo-labeled LDL in HepG2 cells, a human hepatocellular carcinoma line with endogenous expression of LDLR. More specifically, overnight incubation with exogenous, recombinant, human PCSK9 significantly reduced the uptake of pHrodo-labeled LDL-C to 31% of the control (Figure 8B-8D) as anticipated. Pretreatment of the HepG2 cultures with 100 "g / mL of affinity purified anti-PCSK9 antibody, however, was sufficient to restore LDL uptake to 38% of its baseline value even in the presence of inhibitory PCSK9 (Figure 8B, 8C, 8E). The potency and efficacy of VXX-401-induced antibodies were further compared to a therapeutic monoclonal antibody against PCSK9, evolocumab. All antibodies demonstrated dose-dependent inhibition of PCSK9 (Table 8). ^ ^ Attorney Docket No. VXH-00225 ^ Table 7: Binding Potency of VXX-401 Antibodies Versus Evolocumab to PCSK9 AAffinity purified antibodies from VXX-401-treated cynomolgus monkeys. Table 8: LDL-pHrodo Uptake EC50 Values for VXX-401 Antibodies and Evolocumab AAffinity purified antibodies from VXX-401-treated cynomolgus monkeys. VXX-401 Induces Primarily IgG Response Immune response was evaluated similarly as in Example 1. The type of immune response induced by VXX-401 was characterized by investigating the anti-PCSK9 antibody isotypes, the response of PBMCs to various components of the peptide immunogen, as well as the serum cytokine profiles during immunization. The presence of IgG and IgM vaccine- derived antibody isotypes was evaluated over the course of the GLP toxicity. Notably, VXX- 401 was found to specifically evoke an IgG antibody response, which occurred in the absence of detectable IgM (Figure 9). Indeed, IgG antibody reached peak titers (i.e., average EC50 of 3,598) by week 9 of the GLP toxicity study in the 100 "g dosage group whereas no IgM were detected for the study duration (Figure 9A). IgG subtyping analyses of the 100 ug dosage group at week 9 in the repeat dosing study revealed that the IgG produced by VXX-401 immunization were exclusively IgG1 (Figure 9B). This trend held for the other dosage groups as well. Immunoglobulin G, or IgG, is among the most prevalent proteins in human serum, comprising up to 20% of total plasma protein. IgG can be further divided into four subclasses (IgG1, 2, 3, and 4). IgG1 accounts for 60 to 65% of the IgG subclass and is predominantly responsible for the immune response against soluble proteins and peptide antigens. The results showing that VXX-401 elicited a IgG1-dominant response were therefore anticipated, given its nature as a synthetic peptide-based vaccine. Most importantly, the presence of IgG1 in the absence of a detectable IgM response against PCSK9 strongly suggests a lack of innate immunity and a safe, humoral response to vaccination. ^ ^ Attorney Docket No. VXH-00225 ^ Further supporting the lack of an innate immune response was the absence of cytokine response in naïve PBMCs stimulated with various components of the peptide immunogen. Indeed, PBMCs collected from NHPs prior to immunization with 100ug VXX-401 did not release IFNgamma or IL-4 upon stimulation with any of the peptide components of p5494kb, as measured by ELISpot immunoassays (Figure 10A-10B). In contrast, PBMCs collected post-immunization released IFN-; and IL-4 in response to the stimulation with the T-helper peptide alone or the full synthetic peptide immunogen (Figure 11). Importantly, the PCSK9 B-cell epitope alone did not induce a cytokine response in PBMCs collected after immunization, indicating that endogenous PCSK9 will not be recognized as an antigen by the immune system. The latter observation is consistent with the limited duration of the antibody titers seen in vivo. As anticipated, the PBMCs collected pre- and post-immunization showed a strong cytokine response to the PHA positive controls and minimal signal was observed in the unstimulated controls (Figure 10E-10F), which was subtracted as baseline. The in vivo cytokine response profile to VXX-401 was evaluated pre- and post- immunization. Serum concentrations of IFN-;, IL-1^, IL-2, IL-4, IL-6, IL-8, IL-13, IL-10, and TNF- were quantified 2 h before and 6 h after the first, second, third, and fourth injections in the dose-ranging study in cynomolgus monkeys (Table 9). In Table 9, the data are expressed as log2fold-change (log2FC) between pre- versus post-dose. VXX-401 did not induce any change in serum concentrations of IFN- ;, IL-2, IL-4, IL-13, IL-10, and TNF- across all conditions examined. A marginal decrease in serum IL-1^ and IL-8 was observed in most dosing groups relative to their baseline values (log2FC values < -1.0). In contrast, a slight increase in serum IL-6 was observed between pre- and post-dose measurements. ^ ^ Attorney Docket No. VXH-00225 ^ Table 9: Log2fold-change Pre- vs. Post-dose for MSD Cytokines In conclusion, immunization with VXX-401 induced the production of antibodies that recognize and bind to endogenous PCSK9, thus prompting a reduction in LDL-C. More specifically, pharmacology studies in cynomolgus monkeys indicated that VXX-401 is highly immunogenic and reduces LDL-C by 30 to 40% without alterations in serum HDL cholesterol. In vitro analyses further confirmed that VXX-401 induces the production of anti- PCSK9 antibodies with potent binding properties that demonstrate PCSK9-blocking properties in an LDL uptake assay in hepatic cells. Importantly, VXX-401 induced a safe humoral response and was well-tolerated, with no evidence of autoimmunity or chronic ^ ^ Attorney Docket No. VXH-00225 ^ inflammation. immunization of cynomolgus monkeys with VXX-401 induced a safe immune response and robust titers that reached peak levels within a few weeks following a 3-dose priming regimen. In the longitudinal studies, antibody titers progressively decreased and returned to baseline within weeks or months following the priming regimen. However, a single administration of a VXX-401 boost was sufficient to restore maximal antibody titers. That the antibody titers progressively decreased after a priming or boost regimen was positive from a safety standpoint and suggested that boosting every 2 or 3 months might be necessary to maintain a sustained response. With regards to cell-mediated immunity and autoimmunity, VXX-401 was found to safely overcome immune tolerance without generating a targeted T-cell response against PCSK9 or chronic inflammation. As shown by ELISpot, stimulation with the B-cell epitope alone (i.e., p5494a) failed to induce the production of both IFN-; and IL-4, whereas the T- helper peptide and its PCSK9 conjugate (i.e., p5494kb) elicited a robust cytokine response in post-immune PBMCs. These data indicate that, following immunization, the production of anti-PCSK9 antibodies requires regular re-exposure to VXX-401 and will not be perpetuated by the endogenous target. Thus, the immune response will naturally wane in the absence of additional boosts, which is consistent with the progressive return to baseline of serum antibody titers and LDL-C in monkeys. Further bolstering the safety profile of VXX-401, analyses of serum samples collected pre- and post-injection revealed negligible fluctuations in pro-inflammatory cytokines. Overall, the levels of cytokines remained comparable before and after dosing, with no significant differences between any of the groups. These findings were further corroborated by the results of the GLP toxicity study, which did not reveal any significant, sustained, oscillations in IFN-;, IL-1^, IL-6, or TNF- . This is noteworthy in so far that IFN-; and TNF- are associated with cell-mediated immunity, whereas IL-1^ and IL- 6 are potent pro-inflammatory cytokines related to autoimmunity. Thus, these results demonstrate that treatment with VXX-401 does not induce a significant pro-inflammatory response. Additionally, VXX-401 specifically induces anti-PCSK9 IgG1. The lack of IgM, IgG2, IgG3 or IgG4 further demonstrated the nature of the safe humoral response induced by VXX-401. In addition, it is noted that the data for anti-CGRP and anti-PCSK9 peptide immunogen vaccines disclosed herein is consistent with the data obtained by the inventors for peptide immunogen vaccines targeting -synuclein and A^, where such vaccines also comprised an aluminum based adjuvant, as described herein. In particular, administration of an -synuclein peptide immunogen vaccine (ISITEIKGVIVHRIETILF-^k-kkk- 77 ^ ^ Attorney Docket No. VXH-00225 ^ EMPSEEGYQD^^*@A^2B^+-:^$%) induced production of IgG1 antibodies to -synuclein in humans with no detectable production of IgM antibodies. Furthermore, it is noted the peptide immunogen vaccine that does not comprise any adjuvant was found by the inventors to be immunogenic in an animal model. In particular, a PCSK9 peptide immunogen vaccine in a saline solution without an adjuvant induced production of antibodies to PCSK9. It should be understood that any use of sub-headings herein is for organizational purposes, and should not be read to limit the application of those sub-headed features to the various embodiments herein. The disclosure is also not limited to the exemplary embodiments presented herein. Each feature described herein is applicable and usable in all the various embodiments discussed herein and all features described herein can be used in any contemplated combination, regardless of the specific example embodiments that are described herein. EQUIVALENTS Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the claims that follow. INCORPORATION BY REFERENCE All publications, patents, and patent applications referenced herein are hereby incorporated by reference in their entirety as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference. ^ ^

Claims

Attorney Docket No. VXH-00225 ^ What is Claimed Is:

1. A method of inducing production of IgG1 antibodies against a B cell epitope in a subject in need thereof, without substantial production of IgM antibodies, comprising administering to the subject an effective amount of a peptide immunogen composition comprising a peptide immunogen, wherein the peptide immunogen comprises a heterologous artificial ^^^^^^^^^^^^^^^^^^^^^^^D^^^^^^^^^^^^^^ wherein the peptide immunogen composition does not comprise an adjuvant or comprises a compatible adjuvant in an amount of up to about 1.6 mg / mL, wherein the ^^^^^^^^^^^^^I^8^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^and wherein the peptide immunogen composition may comprise a polyanionic CpG oligonucleotide but does not comprise an adjuvant other than the compatible adjuvant.

2. The method of claim 1, which comprises administering the peptide immunogen composition to the subject over a period of time of at least 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, or 15 years.

3. A method of inducing long-term production of IgG1 antibodies against a B cell epitope in a subject in need thereof, comprising administering at least 4 times an effective amount of a peptide immunogen composition to a subject over a period of time of at least 1 year, wherein the peptide immunogen composition comprises a peptide immunogen, wherein the peptide immunogen comprises a heterologous artificial Th epitope linked to a B cell ^^^^^^^^ wherein the peptide immunogen composition does not comprise an adjuvant or comprises a compatible adjuvant in an amount of up to about 1.6 mg / mL, wherein the ^^^^^^^^^^^^^I^8^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^and wherein the peptide immunogen composition may comprise a polyanionic CpG oligonucleotide but does not comprise an adjuvant other than the compatible adjuvant.

4. The method of any one of claims 1-3, wherein the subject is suffering from, or at risk of, a disease or condition associated with, or caused by, a target antigen comprising the B cell epitope. ^ ^Attorney Docket No. VXH-00225 ^ 5. The method of claim 4, wherein the disease or condition is a chronic disease or condition, an autoimmune disease or condition, a chronic inflammation, a neurodegenerative disease or condition, a cancer, or an allergic disease or condition.

6. The method of any one of claims 1-5, wherein the one or more aluminum salts is aluminum phosphate and / or aluminum hydroxide.

7. The method of any one of claims 1-6, wherein the compatible adjuvant is in an amount of about 0.8 mg / mL to about 1.6 mg / mL, optionally wherein the compatible adjuvant is in an amount of about 1.6 mg / mL.

8. The method of any one of claims 1-7, wherein the peptide immunogen composition comprises a polyanionic CpG oligonucleotide^^^^^^^^^^^0^wherein the polyanionic CpG oligonucleotide is CpG1 or CpG3^^^^^^^^^^^0^wherein the polyanionic CpG is CpG1 having the sequence of 5’ TCgTCgTTTTgTCgTTTTgTCgTTTTgTCgTT 3’ (SEQ ID NO: 81), which is fully phosphorothioated.

9. The method of claim 8, wherein the polyanionic CpG oligonucleotide is present in an amount up to about 200 µg / mL^^^^^^^^^^^0^wherein the polyanionic CpG oligonucleotide is present in an amount of about 100 µg / mL to about 200 µg / mL.

10. The method of any one of claims 1-9, wherein the peptide immunogen comprises one of the following formulae: (Th)m-(A)n-(B)-X or (B)-(A)n-(Th)m-X, wherein: Th is the heterologous artificial ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ (A)nis a heterologous linker, wherein A is a naturally occurring amino acid and / or a non- naturally occurring amino acid^^^^^^^^^^^^^^^^^^^^ B is the B cell epitope, optionally wherein the B cell epitope comprises 6 to 50 or 7 to 15 ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ X is an -COOH or -CONH2group of an amino acid.

11. The method of claim 9, wherein n is 1 to 4, and wherein m is 1.

12. The method of claim 10 or 11, wherein the peptide immunogen does not comprise any other epitope, peptide or protein sequence. ^ ^Attorney Docket No. VXH-00225 ^ 13. The method of any one of claims 10-12, wherein the heterologous linker comprises one or more amino acid lysine, optionally wherein the heterologous linker comprises three or four lysines, optionally wherein the linker is ^K-KKK (SEQ ID NO: 130) or KKK-^K (SEQ ID NO: 129)^ 14. The method of any one of claims 1-13, wherein the heterologous artificial Th epitope has an amino acid sequence ISIXEIXXVIVIVXXIEXILF (SEQ ID NO: 132), wherein X is any amino acid^ optionally wherein the heterologous artificial Th epitope has the amino acid sequence ISITEIKGVIVHRIETILF (SEQ ID NO: 32) or ISISEIKGVIVHKIETILF (SEQ ID NO: 30)^^^^^^^^^^^0^wherein the heterologous artificial Th epitope has the amino acid sequence ISITEIKGVIVHRIETILF (SEQ ID NO: 32).

15. The method of any one of claims 1-14, wherein the B cell epitope does not comprise a Th epitope, and / or wherein the peptide immunogen does not comprise an endogenous Th epitope or does not comprise a naturally occurring Th epitope.

16. The method of any one of claims 1-15, wherein the B cell epitope is a peptide from alpha-synuclein protein, Tau protein, ^ amyloid protein, calcitonin gene-related peptide (CGRP), proprotein convertase subtilisin / kexin type 9 (PCSK9), interleukin-31, membrane- bound IgE, or IAPP^^^^^^^^^^^^^^^^^^^^^^0^^^^^^^8^^^^^^^^^^^^^^^^^^^D^^^^^^^^^^^^^# 17. The method of any one of claims 1-15, wherein the B cell epitope is of the amino acid sequence of EMPSEEGYQD (SEQ ID NO: 8), VPTNVGSKAF (SEQ ID NO: 51), SIPWNLERIT (SEQ ID NO: 55), DAEFRHDSGYEVHH (SEQ ID NO: 1), IKHVPGGGSVQIVYK (SEQ ID NO: 13), or DHAGTYGLGD (SEQ ID NO: 15).

18. The method of any one of claims 1-12, wherein the peptide immunogen is ISITEIKGVIVHRIETILF-linker-EMPSEEGYQD, ISITEIKGVIVHRIETILF-linker- VPTNVGSKAF, SIPWNLERIT-linker-ISITEIKGVIVHRIETILF, DAEFRHDSGYEVHH- linker-ISITEIKGVIVHRIETILF, ISITEIKGVIVHRIETILF-linker-IKHVPGGGSVQIVYK, or DHAGTYGLGD-linker-ISITEIKGVIVHRIETILF^^?^^^^^^^^^^^^^^^^^^^^^^K-KKK (SEQ ID NO: 130) or KKK-^k (SEQ ID NO: 129).

19. The method of any one of claims 1-18, wherein the peptide immunogen is not or does not comprise the amino acid sequence ISITEIKGVIVHRIETILF-^K-KKK-EMPSEEGYQD (SEQ ID NO: 92), or the B cell epitope is not or does not comprise the amino acid sequence EMPSEEGYQD (SEQ ID NO: 8). ^ ^Attorney Docket No. VXH-00225 ^ 20. The method of any one of claims 1-19, which comprises the peptide immunogen in an amount from about 10 to 2000 µg / mL^^^^^^^^^^^0^which comprises the peptide immunogen in an amount from about 10 to about 1000 µg / mL^^^^^^^^^^^0^which comprises the peptide immunogen in an amount from about 10 to 500 µg / mL^^^^^^^^^^^0^which comprises the peptide immunogen in an amount from about 100 to 400 µg / mL^^^^^^^^^^^0^which comprises the peptide immunogen in an amount of about 300 µg / mL.

21. The method of any one of claims 1-20, wherein administering is intramuscular.

22. The method of any one of claims 1-21, wherein administering comprises administering at least 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 times to the subject^^^^^^^^^^^0^wherein administering comprises administering every 8 weeks to 6 months.

23. The method of any one of claims 1-22, wherein administering comprises administering a priming regimen of 1 to 3 doses within about 4-12 weeks, followed by administering of a booster dose every 4 weeks to 6 months^^^^^^^^^^^0^wherein the priming regimen comprises 2 or 3 doses^ optionally wherein the priming regimen is administered at weeks 0, 3 and 6.

24. The method of any one of claims 1-23, which does not comprise administration of an anti-inflammatory drug conjointly with the peptide immunogen composition^^^^^^^^^^^0^ wherein the anti-inflammatory drug is a corticosteroid, a nonsteroidal anti-inflammatory drug (NSAID), an antileukotriene, and / or an immune selective anti-inflammatory derivative (ImSAID).

25. The method of any one of claims 1-24, wherein the subject is a human.

26. The method of any one of claims 1-25, wherein administering the peptide immunogen composition, when assessed from about week 1 to about week 16 after administration, induces (i) production of IgG1 isotype antibodies to the B cell epitope in the subject, and (ii) substantially higher production of IgG1 antibodies than IgM antibodies, wherein substantially higher is at least 10, 15 or 20 times higher.

27. The method of any one of claims 1-26, wherein administering the peptide immunogen composition, when assessed from about week 1 to about week 16 after administration, does not induce production, or induces no detectable production, of IgM antibodies in the subject. ^ ^Attorney Docket No. VXH-00225 ^ 28. The method of any one of claims 1-27, wherein administering the peptide immunogen composition, when assessed from about week 1 to about week 16 after administration, induces substantially higher production of IgG1 isotype antibodies than IgG2, IgG3 and / or IgG4 isotype antibodies to the B cell epitope in the subject, wherein substantially higher is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher^^^^^^^^^^^0^wherein administering the peptide immunogen composition substantially does not induce, or induces no detectable, production of IgG2, IgG3 and / or IgG4 isotype antibodies in the subject.

29. A peptide immunogen composition comprising: a peptide immunogen comprising one of the following formulae: (Th)m-(A)n-(B)-X or (B)-(A)n-(Th)m-X, wherein: Th is the heterologous artificial ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ (A)n is a heterologous linker, wherein A is a naturally occurring amino acid and / or a non- ^^^^^^^^0^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ B is the B cell epitope, optionally wherein the B cell epitope comprises 6 to 50 or 7 to 15 ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ X is an -COOH or -CONH2 ^^^^^^^^^^^^^^^^^^^^^^^ wherein the peptide immunogen composition (i) does not comprise an adjuvant or comprises a compatible adjuvant in an amount of up to about 1.6 mg / mL, wherein the compatible adjuvant is one or more aluminum salts, optionally wherein the one or more aluminum salts ^^^^^^^^^^^^^^^^^^^^^^^^^.^^^^^^^^^^^^^0^^^C^^^^^^^^^1^^!^^^^^^^^^^0^ further comprises a polyanionic CpG oligonucleotide but does not comprise an adjuvant other than the compatible adjuvant.

30. The peptide immunogen composition of claim 29, wherein n is 1 to 4, and m is 1.

31. The peptide immunogen composition of claim 29 or 30, wherein the peptide immunogen does not comprise any other epitope, peptide or protein sequence.

32. The peptide immunogen composition of any one of claims 29-31, wherein the one or more aluminum salts is aluminum phosphate. ^ ^Attorney Docket No. VXH-00225 ^ 33. The peptide immunogen composition of any one of claims 29-32, wherein the compatible adjuvant is in an amount of about 0.8 mg / mL to about 1.6 mg / mL^^^^^^^^^^^0^ wherein the compatible adjuvant is in an amount of about 1.6 mg / mL.

34. The peptide immunogen composition of any one of claims 29-33, which comprises a polyanionic CpG oligonucleotide^^^^^^^^^^^0^wherein the polyanionic CpG oligonucleotide is CpG1 or CpG3^^^^^^^^^^^0^wherein the polyanionic CpG oligonucleotide is CpG1 having the sequence of 5’ TCgTCgTTTTgTCgTTTTgTCgTTTTgTCgTT 3’ (SEQ ID NO: 81), which is fully phosphorothioated.

35. The peptide immunogen composition of claim 34, wherein the polyanionic CpG oligonucleotide is present in an amount up to about 200 µg / mL^^^^^^^^^^^0^wherein the polyanionic CpG oligonucleotide is present in an amount of about 100 µg / mL to about 200 µg / mL^^^^^^^^^^^0^wherein the polyanionic CpG oligonucleotide is present in an amount of about 200 µg / mL.

36. The peptide immunogen composition of any one of claims 29-35, wherein the heterologous artificial Th epitope has an amino acid sequence of ISIXEIXXVIVIVXXIEXILF (SEQ ID NO: 132), wherein X is any amino acid^ optionally wherein the heterologous artificial Th epitope has the amino acid sequence ISITEIKGVIVHRIETILF (SEQ ID NO: 32) or ISISEIKGVIVHKIETILF (SEQ ID NO: 30).

37. The peptide immunogen composition of any one of claims 29-36, wherein the B cell epitope does not comprise a Th epitope, and / or wherein the peptide immunogen does not comprise an endogenous Th epitope or does not comprise a naturally occurring Th epitope^^ optionally wherein the peptide immunogen does not comprise a Th epitope naturally occurring in a pathogen protein, wherein the pathogen protein is Measles Virus Fusion (MVF) protein, Hepatitis B Surface Antigen (HBsAg), influenza protein, Clostridium tetani protein, Bordetella protein, Diphtheria protein, Plamsodium falciparum protein, Schistosoma mansoni protein, MCMV protein, or Epstein-Barr virus (EBV) protein.

38. The peptide immunogen composition of any one of claims 29-37, wherein the B cell epitope is a peptide from a protein associated with or involved in pathogenesis of a disease or condition^^^^^^^^^^^0^wherein the disease or condition is a chronic disease or condition, neurodegenerative disease or condition, allergic disease or condition, or a cancer^^^^^^^^^^^0^ wherein the disease or condition is tauopathy, Alzheimer’s, synucleinopathy, Parkinson’s, dementia with Lewy bodies (DLB), multiple system atrophy (MSA), migraine, ^ ^Attorney Docket No. VXH-00225 ^ hypercholesterolemia, hyperlipidemia, or atopic dermatitis^^^^^^^^^^^0^wherein the B cell epitope is a peptide from alpha-synuclein protein, Tau protein, ^ amyloid protein, calcitonin gene-related peptide (CGRP), proprotein convertase subtilisin / kexin type 9 (PCSK9), interleukin-31, or membrane-bound IgE^^^^^^^^^^^^^^^^^^^^^^0^^^^^^^8^^^^^^^^^^^^^^^^^^^D^ cell epitope.

39. The peptide immunogen composition of any one of claims 29-38, wherein the B cell epitope is of the amino acid sequence of EMPSEEGYQD (SEQ ID NO: 8), VPTNVGSKAF (SEQ ID NO: 51), SIPWNLERIT (SEQ ID NO: 55), DAEFRHDSGYEVHH (SEQ ID NO: 1), IKHVPGGGSVQIVYK (SEQ ID NO: 13), or DHAGTYGLGD (SEQ ID NO: 15).

40. The peptide immunogen composition of any one of claims 29-39, wherein the heterologous linker comprises one or more amino acid lysine^ optionally wherein the heterologous linker comprises three or four lysines^ optionally wherein the linker is ^K-KKK (SEQ ID NO: 130) or KKK-^k (SEQ ID NO: 129).

41. The peptide immunogen composition of any one of claims 29-35, wherein the peptide immunogen is ISITEIKGVIVHRIETILF-linker-EMPSEEGYQD, ISITEIKGVIVHRIETILF- linker-VPTNVGSKAF, SIPWNLERIT-linker-ISITEIKGVIVHRIETILF, DAEFRHDSGYEVHH-linker-ISITEIKGVIVHRIETILF, ISITEIKGVIVHRIETILF-linker- IKHVPGGGSVQIVYK, or DHAGTYGLGD-linker-ISITEIKGVIVHRIETILF^^?^^^^^^^^^^^ linker is ^K-KKK (SEQ ID NO: 130) or KKK-^K (SEQ ID NO: 129).

42. The peptide immunogen composition of any one of claims 29-41, wherein the peptide immunogen is not or does not comprise the amino acid sequence ISITEIKGVIVHRIETILF- ^K-KKK-EMPSEEGYQD (SEQ ID NO: 92), or the B cell epitope is not or does not comprise the amino acid sequence EMPSEEGYQD (SEQ ID NO: 8).

43. The peptide immunogen composition of any one of claims 29-42, which comprises the peptide immunogen in an amount from about 10 to 2000 µg / mL^^^^^^^^^^^0^which comprises the peptide immunogen in an amount from about 10 to about 1000 µg / mL^^ optionally which comprises the peptide immunogen in an amount from about 10 to 500 µg / mL^^^^^^^^^^^0^which comprises the peptide immunogen in an amount from about 100 to 400 µg / mL^^^^^^^^^^^0^which comprises the peptide immunogen in an amount of about 100 or 300 µg / mL. ^ ^Attorney Docket No. VXH-00225 ^ 44. The peptide immunogen composition of any one of claims 29-43, which when administered to a mammal induces production of IgG isotype antibodies to the B cell epitope, optionally wherein IgG antibody production is assessed from about week 1 to about week 12 after administration^^^^^.^^^which when administered to a mammal induces substantially higher production of IgG antibodies than IgM antibodies to the B cell epitope, optionally wherein antibody production is assessed from about week 1 to about week 12 after administration, optionally wherein substantially higher is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher.

45. The peptide immunogen composition of claim 44, wherein the IgG antibodies are of IgG1 isotype.

46. The peptide immunogen composition of any one of claims 29-45, which when administered to a mammal substantially does not induce production, or induces no detectable production, of IgM antibodies, optionally wherein IgM antibody production is assessed from about week 1 to about week 12 after administration.

47. The peptide immunogen composition of any one of claims 29-46, which when administered to a mammal induces substantially higher production of IgG1 isotype antibodies than IgG2, IgG3 and / or IgG4 isotype antibodies to the B cell epitope, optionally wherein antibody production is assessed from about week 1 to about week 12 after administration, optionally wherein substantially higher is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 times higher.

48. The peptide immunogen composition of any one of claims 29-47, which when administered to a mammal substantially does not induce production, or induces no detectable production, of IgG2, IgG3 and / or IgG4 isotype antibodies, optionally wherein antibody production is assessed from about week 1 to about week 12 after administration.

49. The peptide immunogen composition of any one of claims 29-48, which when administered to a mammal substantially does not induce, or induces no detectable, innate immunity or T cell inflammation, optionally wherein the innate immunity or T cell inflammation is assessed from about week 1 to about week 12 after administration.

50. The peptide immunogen composition of any one of claims 44-49, wherein the mammal is a human or a non-human primate. ^ ^

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