Nanoparticle compositions associated with peptides

Abstract

The present invention relates to compositions comprising sHDL nanoparticles. In particular, the present invention relates to sHDL nanoparticles comprising a phospholipid; an apoplipoprotein mimetic; a thiol-reactive lipid; and a peptide comprising a linker moiety connected with a payload moiety, wherein the linker comprises cysteine (C) and one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S), the payload comprises a polypeptide that is 5 to 35 amino acids in length and has a net positive charge at a pH of 7 to 12, and the peptide comprises a net negative charge at a pH of 7 and an isoelectric point of 0.4 to 12; and wherein the peptide is covalently attached to the thiol-reactive lipid by way of the cysteine (C).

Description

[0001] UM-41715.601 NANOPARTICLE COMPOSITIONS ASSOCIATED WITH PEPTIDES CROSS-REFERENCE TO RELATED APPLICATIONS The present application claims priority to U.S. Provisional Application No.63 / 522,816, filed June 23, 2023, which is incorporated herein by reference in its entirety. STATEMENT OF GOVERNMENT SUPPORT This invention was made with government support under DE030691 awarded by the National Institutes of Health. The government has certain rights in the invention. SEQUENCE LISTING The text of the computer readable sequence listing filed herewith, titled “UM_41715_601_SequenceListing.xml” created June 18, 2024, having a file size of 671,386 bytes, is hereby incorporated by reference in its entirety. FIELD OF THE INVENTION The present invention relates to compositions comprising sHDL nanoparticles. In particular, the present invention relates to sHDL nanoparticles comprising a phospholipid; an apoplipoprotein mimetic; a thiol-reactive lipid; and a peptide comprising a linker moiety connected with a payload moiety, wherein the linker comprises cysteine (C) and one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S), the payload comprises a polypeptide that is 5 to 35 amino acids in length and has a net positive charge at a pH of 7 to 12, and the peptide comprises a net negative charge at a pH of 7 and an isoelectric point of 0.4 to 12; and wherein the peptide is covalently attached to the thiol-reactive lipid by way of the cysteine (C). BACKGROUND OF THE INVENTION Peptide-based therapeutics are gaining strong interest as candidates for clinical application owing to high specificity, potency, low toxicity, and good tolerance [1, 2]. In addition, the major advantage of peptide-based therapeutics is the ability to generate different specific sequences, leading to a huge functional diversity. To date more than 80 peptide-based drugs have been approved for therapeutics against a variety of diseases, including HIV infection, chronic pain, cancer, diabetes, multiple sclerosis, and osteoporosis [3]. In general, peptides are signaling molecules that trigger intracellular effects by binding to specific cell surface receptors or ion channels. However, the vast majority of peptides cannot autonomously exit UM-41715.601 endolysosomes or penetrate cell membranes [4]. Furthermore, low plasma stability, short circulation time, low oral bioavailability, and high cost of large-scale manufacturing significantly limit the use of peptide drugs [5]. These shortcomings of peptides can be overcome by developing new drug delivery systems. For this purpose, a large number of peptide / protein delivery systems have been proposed, including those using lipid nanocarriers [6, 7], polymers [8, 9], mesoporous silica nanoparticles

[0010] , cell-penetrating peptides [11, 12], and various other approaches [13-16]. Remarkably, synthetic high-density lipoprotein (sHDL) nanodiscs (NDs) have shown promise as carriers in peptide delivery studies [17, 18]. sHDL NDs have all the advantages of lipid nanoparticles and liposomes, and even surpass them since sHDL NDs exhibit long circulation, good tolerance, and high stability

[0019] . Moreover, the receptor-mediated ability to internalize cells and the unique ultra-small size of about 10 nm make sHDL a promising vehicle for tissue penetration and high intracellular accumulation, which is especially useful for such applications as drug delivery to tumors [20-22]. A range of sHDL-based ND delivery systems consisting of phospholipids and apolipoprotein A1 mimetic peptides have been previously developed [23-28]. In a conventional approach, a "Cys-Ser-Ser" linker was added to the N-terminus of peptides and thiol-chemistry used to conjugate the peptides to lipids. The resulting peptide-lipid conjugates were then loaded onto pre-formed NDs. While this strategy worked for many peptides, this approach has been shown to be not universally applicable. For instance, hydrophobic peptides and those with the isoelectric points near the pH of the solution tend to form some aggregates when incorporated into NDs [29, 30]. In addition, although peptides with neutral charge exhibit propensity for aggregation, peptides with a high positively charged isoelectric point at pH 7 also form aggregates [31, 32]. In this context, arginines are more prone to aggregation than lysines, which is caused by a greater propensity of the Arg side chain to form protein-to-protein interactions

[0033] . Improved compositions and methods for delivering peptides are needed. The present invention addresses these needs. SUMMARY OF THE INVENTION Experiments conducted during the course of developing embodiments for the present invention resulted in the development of a new strategy for attaching negatively or positively charged amino acids either at the C or N terminus to increase the aqueous solubility of peptides and to improve the manufacturability of peptide-loaded sHDL NDs. Such experiments UM-41715.601 demonstrated that for peptides with a high isoelectric point (pI), the addition of negatively charged amino acids (such as aspartic acid or glutamic acid) to the peptide sequence leads to the conversion of the net charge from a positive to a negative value at pH 7. Such charge conversion allows for efficient and robust loading of peptide-lipid conjugates onto NDs, resulting in homogeneous and uniform peptide-loaded NDs. Thus, the addition of negatively or positively charged amino acids either at C or N terminus of peptides offers a universal strategy for improving the incorporation of peptides to NDs and for improving the manufacturing of peptide- NDs products. Additionally, our approach demonstrates versatility in using peptides with cysteine residues not only at the N-terminus but also at the C-terminus or non-terminal positions to obtain peptide-loaded sHDL NDs. Overall, embodiments described herein pertain to a new composition of matter that improves the incorporation of various peptides into NDs and the manufacturing of peptide-NDs products. Also, this approach may be generally applicable for incorporating various peptides into other nanoparticles and polymers. Accordingly, in certain embodiments, the present invention provides compositions comprising sHDL nanoparticle. In some embodiments, the sHDL nanoparticles comprising a phospholipid; an apoplipoprotein mimetic; a thiol-reactive lipid; and a peptide comprising a linker moiety connected with a payload moiety, wherein the linker comprises either: [cysteine (C) and optionally one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S)] or [D-D or D-D-D if the payload includes a C amino acid], the payload comprises a polypeptide that is 5 to 35 amino acids in length and has a net positive charge at a pH of 7 to 12, and the peptide comprises a net negative charge at a pH of 7 and an isoelectric point of 0.4 to 12; and wherein the peptide is covalently attached to the thiol-reactive lipid by way of the linker. In some embodiments, the peptide is covalently attached to the thiol-reactive lipid by way of the Cys. In some embodiments, the peptide is covalently attached to the thiol-reactive lipid by way of the carboxy terminus of the Cys. In some embodiments, the peptide is covalently attached to the thiol-reactive lipid by way of the amino terminus of the Cys. In some embodiments, the peptide is covalently attached to the thiol-reactive lipid by way of a non- terminal position terminus of the Cys. In some embodiments, if the payload includes a C amino acid, the peptide is covalently attached to the thiol-reactive lipid by way of the linker, wherein the linker comprises D-D or D- D-D. In some embodiments, the peptide comprises the formula: [linker]-[payload] or [payload]-[linker]. UM-41715.601 In some embodiments, the payload has a net positive charge at a pH of 7 to 12. In some embodiments, the payload has a net zero charge at a pH of 7 to 12. In some embodiments, the payload has a net negative charge at a pH of 7 to 12. In some embodiments, the peptide has a charge of less than -0.1. In some embodiments, the peptide has a charge ranging from -0.1 to -5.0. In some embodiments, the peptide comprises an isoelectric point of 3.7 to 12. In some embodiments, the peptide comprises an isoelectric point of 0.62 to 9.78. In some embodiments, the linker sequence is C. In some embodiments, the linker sequence is DDCDD. In some embodiments, the linker sequence is D-D or DDD if the payload includes a C amino acid. In some embodiments, the one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S) comprises a peptide dimer. In some embodiments, the peptide dimer is selected from DD, SE, SD, and EE. In some embodiments, the one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S) comprises a peptide trimer. In some embodiments, the peptide trimer is selected from DDD, EEE, and KEE. In some embodiments, the one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S) comprises a peptide 4-mer. In some embodiments, the peptide 4-mer is selected from DDDD (SEQ ID NO:762) and EEEE (SEQ ID NO:763). In some embodiments, the payload has a charge of greater than 0.1 at pH 7. In some embodiments, the payload has a charge ranging from 0.1 to 5.0. In some embodiments, the payload is a polypeptide that is 12 to 35 amino acids in length. In some embodiments, the payload is selected from GWYRSPFSRVVHL (SEQ ID NO:764), NTWTTSQSIAFPSK (SEQ ID NO:765), KVAPVWVRMME (SEQ ID NO:766), KYNKANAFL (SEQ ID NO:767), and ASFEAQGALANIAVDKA (SEQ ID NO:768). In some embodiments, the apolipoprotein mimetic is an ApoA-I mimetic, having a sequence of any of SEQ ID NOs: 1-336 and WDRVKDLATVYVDVLKDSGRDYVSQF (SEQ ID NO:341), LKLLDNWDSVTSTFSKLREOL (SEQ ID NO:342), PVTOEFWDNLEKETEGLROEMS (SEQ ID NO:343), KDLEEVKAKVQ (SEQ ID NO: 344), KDLEEVKAKVO (SEQ ID NO: 345), PYLDDFQKKWQEEMELYRQKVE (SEQ ID NO: 346), PLRAELQEGARQKLHELOEKLS (SEQ ID NO: 347), PLGEEMRDRARAHVDALRTHLA (SEQ ID NO: 348), PYSDELRQRLAARLEALKENGG (SEQ ID NO: 349), ARLAEYHAKATEHLSTLSEKAK (SEQ ID NO: 350), PALEDLROGLL (SEQ ID NO: 351), PVLESFKVSFLSALEEYTKKLN (SEQ ID NO:352), UM-41715.601 PVLESFVSFLSALEEYTKKLN (SEQ ID NO:353), PVLESFKVSFLSALEEYTKKLN (SEQ ID NO:352), TVLLLTICSLEGALVRRQAKEPCV (SEQ ID NO: 354) QTVTDYGKDLME (SEQ ID NO:355), KVKSPELOAEAKSYFEKSKE (SEQ ID NO:356), VLTLALVAVAGARAEVSADOVATV (SEQ ID NO:357), NNAKEAVEHLOKSELTOOLNAL (SEQ ID NO:358), LPVLVWLSIVLEGPAPAOGTPDVSS (SEQ ID NO:359), LPVLVVVLSIVLEGPAPAQGTPDVSS (SEQ ID NO:360), ALDKLKEFGNTLEDKARELIS (SEQ ID NO: 361), VVALLALLASARASEAEDASLL (SEQ ID NO:362), HLRKLRKRLLRDADDLQKRLAVYOA (SEQ ID NO:363), AQAWGERLRARMEEMGSRTRDR (SEQ ID NO:364), LDEVKEQVAEVRAKLEEQAQ (SEQ ID NO:365), DWLKAFYDKVAEKLKEAF (SEQ ID NO:236), DWLKAFYDKVAEKLKEAFPDWAKAAYDKAAEKAKEAA (SEQ ID NO:366), PVLDLFRELLNELLEALKQKL (SEQ ID NO:367), PVLDLFRELLNELLEALKQKLA (SEQ ID NO:368), PVLDLFRELLNELLEALKQKLK (SEQ ID NO:4), PVLDLFRELLNELLEALKQKLA (SEQ ID NO:369), PVLDLFRELLNELLEALKKLLK (SEQ ID NO:370), PVLDLFRELLNELLEALKKLLA (SEQ ID NO:371), PLLDLFRELLNELLEALKKLLA (SEQ ID NO:372), and EVRSKLEEWFAAFREFAEEFLARLKS (SEQ ID NO: 373). In some embodiments, the apolipoprotein mimetic has the sequence PVLDLFRELLNELLEALKQKLK (SEQ ID NO: 4). In some embodiments, the thiol-reactive lipid is selected from dioleoyl-sn-glycero-3- phosphoethanolamine-N-[3-(2-pyridyldithio) propionate] (DOPE-PDP), 1,2-di-(9Z- octadecenoyl)-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidophenyl)butyramide], 1,2- dihexadecanoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidophenyl)butyramide], 1,2- dihexadecanoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidomethyl)cyclohexane- carboxamide], 1,2-Dioleoyl-sn–glycero-3-phosphoethanolamine-maleimide (DOPE-Mal), and 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine-N-[4-(p- maleimidomethyl)cyclohexane-carboxamide]. In some embodiments, the thiol-reactive lipid is DOPE-PDP. Additional embodiments will be apparent to persons skilled in the relevant art based on the teachings contained herein. UM-41715.601 BRIEF DESCRIPTION OF THE DRAWINGS FIG.1: The size distribution of ND-SIINFEKL (with CSS, CSE or CEE linker) and ND- Ea (with CSS or CSE linker) as measured by DLS in 10 mM phosphate buffer (pH = 7.4). FIG.2: The size distribution of ND-MOG38-50 (with CSS, CDD or CDDD linker) and ND-PLP178-191 (with CSS or CDD linker) as measured by DLS in 10 mM phosphate buffer (pH = 7.4). FIG.3: The size distribution of ND-KV11 (with CSS, CSE or CEE linker) and ND- NRPA7 (with CSS or CEE linker) as measured by DLS in 10 mM phosphate buffer (pH = 7.4). FIG.4: The size distribution of ND-mIns2 B:9-23 (without linker) and ND-HMOG186- 200 (without linker or with DDD linker) as measured by DLS in 10 mM phosphate buffer (pH = 7.4). FIG.5: The size distribution of ND-Gliadin-C1 (without linker) as measured by DLS in 10 mM phosphate buffer (pH = 7.4). DEFINITIONS The term “about” is used herein to mean a value that is ±10% of the recited value. As used herein, by “administering” is meant a method of giving a dosage of a composition described herein to a subject. The compositions utilized in the methods described herein can be administered by any suitable route, including, for example, by inhalation, nebulization, aerosolization, intranasally, intratracheally, intrabronchially, orally, parenterally (e.g., intravenously, subcutaneously, or intramuscularly), orally, nasally, rectally, topically, or buccally. The compositions utilized in the methods described herein can also be administered locally or systemically. The preferred method of administration can vary depending on various factors (e.g., the components of the composition being administered, and the severity of the condition being treated). As used herein, the term “associated with” refers to the state of two or more entities (e.g., nanoparticles and one or more peptides) which are linked by a direct or indirect covalent or non- covalent interaction. In some embodiments, an association is covalent. In some embodiments, a covalent association is mediated by a linker moiety. In some embodiments, an association is non-covalent (e.g., charge interactions, affinity interactions, metal coordination, physical adsorption, host-guest interactions, hydrophobic interactions, TT stacking interactions, hydrogen bonding interactions, van der Waals interactions, magnetic interactions, electrostatic interactions, dipole-dipole interactions, etc.). For example, in some embodiments, a peptide is admixed with a nanoparticle. In some embodiments, a peptide is conjugated with a nanoparticle. UM-41715.601 In some embodiments, a peptide is encapsulated within a nanoparticle. In some embodiments, a peptide is absorbed into a nanoparticle. In some embodiments, a peptide is adsorbed onto a nanoparticle. In some embodiments, a peptide is admixed with a nanoparticle. As used herein, the term “absorbed” refers to a peptide that is taken into and stably retained in the interior, that is, internal to the outer surface, of a nanoparticle and / or microparticle. As used herein, the term “admixed” refers to a peptide that is dissolved, dispersed, or suspended in a nanoparticle and / or microparticle. In some cases, the biomacromolecule agent may be uniformly admixed in the nanoparticle and / or microparticle. As used herein, the term “adsorbed” refers to the attachment of a peptide to the external surface of a nanoparticle and / or microparticle. Such adsorption preferably occurs by electrostatic attraction. Electrostatic attraction is the attraction or bonding generated between two or more oppositely charged or ionic chemical groups. Generally, the adsorption is typically reversible. As used herein, the term “mutein” is intended to include proteins and polypeptides with an altered amino acid sequence and which arise as a result of a mutation or a recombinant DNA procedure. As used herein, a “combination therapy” or “administered in combination” means that two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) different agents or treatments are administered to a subject as part of a defined treatment regimen for a particular disease or condition. The treatment regimen defines the doses and periodicity of administration of each agent such that the effects of the separate agents on the subject overlap. In some embodiments, the delivery of the two or more agents is simultaneous or concurrent and the agents may be co- formulated. In some embodiments, the two or more agents are not co-formulated and are administered in a sequential manner as part of a prescribed regimen. In some embodiments, administration of two or more agents or treatments in combination is such that the reduction in a symptom, or other parameter related to the disorder, is greater than what would be observed with one agent or treatment delivered alone or in the absence of the other. The effect of the two treatments can be partially additive, wholly additive, or greater than additive (e.g., synergistic). Sequential or substantially simultaneous administration of each therapeutic agent can be affected by any appropriate route including, but not limited to, by inhalation, nebulization, aerosolization, intranasally, intratracheally, intrabronchially, orally, parenterally (e.g., intravenously, subcutaneously, or intramuscularly), orally, nasally, rectally, topically, buccally, or by direct absorption through mucous membrane tissues. The therapeutic agents can be administered by UM-41715.601 the same route or by different routes. For example, a first therapeutic agent of the combination may be administered by intravenous injection while a second therapeutic agent of the combination may be administered orally. As used herein, the term "drug" or “therapeutic agent” is meant to include any molecule, molecular complex, or substance administered to an organism for diagnostic or therapeutic purposes, including medical imaging, monitoring, contraceptive, cosmetic, nutraceutical, pharmaceutical, and prophylactic applications. The term drug is further meant to include any such molecule, molecular complex, or substance that is chemically modified and / or operatively attached to a biologic or biocompatible structure. As used herein, the term “fragment” refers to less than 100% of the amino acid sequence of a full-length reference protein (e.g., 99%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, of the full-length sequence etc.), but including, e.g., 5, 10, 20, 25, 30, 35, 40, 45, 50, 100, 150, 200, 250, 300, 350, or more amino acids. A fragment can be of sufficient length such that a desirable function of the full-length protein is maintained. As used herein, the term “expanding” refers to increasing the number of cells in a cell population or sample due to cell replication. As used herein, the term “HDL” or “high density lipoprotein” refers to high-density lipoprotein. HDL comprises a complex of lipids and proteins in approximately equal amounts that functions as a transporter of cholesterol in the blood. HDL is mainly synthesized in and secreted from the liver and epithelial cells of the small intestine. Immediately after secretion, HDL is in a form of a discoidal particle containing apolipoprotein A-I (also called apoA-I) and phospholipid as its major constituents and is also called nascent HDL. This nascent HDL receives, in blood, free cholesterol from cell membranes of peripheral cells or produced in the hydrolysis course of other lipoproteins, and forms mature spherical HDL while holding, at its hydrophobic center, cholesterol ester converted from said cholesterol by the action of LCAT (lecithin cholesterol acyltransferase). HDL plays an extremely important role in a lipid metabolism process called “reverse cholesterol transport”, which takes, in blood, cholesterol out of peripheral tissues and transports it to the liver. High levels of HDL are associated with a decreased risk of atherosclerosis and coronary heart disease (CHD) as the reverse cholesterol transport is considered one of the major mechanisms for HDL’s prophylactic action on atherosclerosis. As used herein, the term “nucleic acid” may be DNA or RNA, such as mRNA. In embodiments, the compositions comprise a complement, such as a full-length complement, or a degenerate (due to degeneracy of the genetic code) of any of the nucleic acids provided herein. UM-41715.601 In embodiments, the nucleic acid is an expression vector that can be transcribed when transfected into a cell line. In embodiments, the expression vector may comprise a plasmid, retrovirus, or an adenovirus amongst others. Nucleic acids can be isolated or synthesized using standard molecular biology approaches, for example by using a polymerase chain reaction to produce a nucleic acid fragment, which is then purified and cloned into an expression vector. Additional techniques useful in the practice of this invention may be found in Current Protocols in Molecular Biology 2007 by John Wiley and Sons, Inc.; Molecular Cloning: A Laboratory Manual (Third Edition) Joseph Sambrook, Peter MacCallum Cancer Institute, Melbourne, Australia; David Russell, University of Texas Southwestern Medical Center, Dallas, Cold Spring Harbor. As used herein, the term “in vitro” refers to an artificial environment and to processes or reactions that occur within an artificial environment. In vitro environments can consist of, but are not limited to, test tubes and cell culture. The term “in vivo” refers to the natural environment (e.g., an animal or a cell) and to processes or reaction that occur within a natural environment. As used here, the term “lipids” or “lipid molecules” refer to fatty substances that are insoluble in water and include fats, oils, waxes, and related compounds. They may be either made in the blood (endogenous) or ingested in the diet (exogenous). Lipids are essential for normal body function and whether produced from an exogenous or endogenous source, they must be transported and then released for use by the cells. The production, transportation, and release of lipids for use by the cells is referred to as lipid metabolism. While there are several classes of lipids, two major classes are cholesterol and triglycerides. Cholesterol may be ingested in the diet and manufactured by the cells of most organs and tissues in the body, primarily in the liver. Cholesterol can be found in its free form or, more often, combined with fatty acids forming what is known as cholesterol esters. As used herein, “lipid” or “lipid molecule” refers to any lipophilic compound. Non-limiting examples of lipid compounds include fatty acids, cholesterol, phospholipids, complex lipids, and derivatives or analogs thereof. They are usually divided into at least three classes: (1) “simple lipids,” which include fats and oils as well as waxes; (2) “compound lipids,” which include phospholipids and glycolipids; and (3) “derived lipids” such as steroids. Lipids or lipid molecules suitable for use in the present invention include both membrane-forming lipids and non-membrane-forming lipids. As used herein the term, “lipoproteins” refer to compounds that are structured so that water-insoluble lipids are contained in a partially water-soluble shell. Depending on the type of UM-41715.601 lipoprotein, the contents include varying amounts of free and esterified cholesterol, triglycerides, and apoproteins or apolipoproteins. There are five major types of lipoproteins, which differ in function and in their lipid and apoprotein content and are classified according to increasing density: (i) chylomicrons and chylomicron remnants, (ii) very low density lipoproteins (“VLDL”), (iii) intermediate-density lipoproteins (“IDL”), (iv) low-density lipoproteins (“LDL”), and (v) high-density lipoproteins (“HDL”). Cholesterol circulates in the bloodstream as particles associated with lipoproteins. The term “non-naturally occurring amino acid,” as used herein, means an alpha amino acid that is not naturally produced or found in a mammal. Examples of non-naturally occurring amino acids include D-amino acids; an amino acid having an acetylaminomethyl group attached to a sulfur atom of a cysteine; a pegylated amino acid; the omega amino acids of the formula NH2(CH2)nCOOH where n is 2-6, neutral nonpolar amino acids, such as sarcosine, t-butyl alanine, t-butyl glycine, N-methyl isoleucine, and norleucine; oxymethionine; phenylglycine; citrulline; methionine sulfoxide; cysteic acid; ornithine; diaminobutyric acid; 3-aminoalanine; 3- hydroxy-D-proline; 2,4-diaminobutyric acid; 2-aminopentanoic acid; 2-aminooctanoic acid, 2- carboxy piperazine; piperazine-2-carboxylic acid, 2-amino-4-phenylbutanoic acid; 3-(2- naphthyl)alanine, and hydroxyproline. Other amino acids are α-aminobutyric acid, α-amino-α- methylbutyrate, aminocyclopropane-carboxylate, aminoisobutyric acid, aminonorbornyl- carboxylate, L-cyclohexylalanine, cyclopentylalanine, L-N-methylleucine, L-N- methylmethionine, L-N-methylnorvaline, L-N-methylphenylalanine, L-N-methylproline, L-N- methylserine, L-N-methyltryptophan, D-ornithine, L-N-methylethylglycine, L-norleucine, α- methyl-aminoisobutyrate, α-methylcyclohexylalanine, D-α-methylalanine, D-α-methylarginine, D-α-methylasparagine, D-α-methylaspartate, D-α-methylcysteine, D-α-methylglutamine, D-α- methylhistidine, D-α-methylisoleucine, D-α-methylleucine, D-α-methyllysine, D-α- methylmethionine, D-α-methylornithine, D-α-methylphenylalanine, D-α-methylproline, D-α- methylserine, D-N-methylserine, D-α-methylthreonine, D-α-methyltryptophan, D-α- methyltyrosine, D-α-methylvaline, D-N-methylalanine, D-N-methylarginine, D-N- methylasparagine, D-N-methylaspartate, D-N-methylcysteine, D-N-methylglutamine, D-N- methylglutamate, D-N-methylhistidine, D-N-methylisoleucine, D-N-methylleucine, D-N- methyllysine, N-methylcyclohexylalanine, D-N-methylornithine, N-methylglycine, N- methylaminoisobutyrate, N-(1-methylpropyl)glycine, N-(2-methylpropyl)glycine, D-N- methyltryptophan, D-N-methyltyrosine, D-N-methylvaline, γ-aminobutyric acid, L-t- butylglycine, L-ethylglycine, L-homophenylalanine, L-α-methylarginine, L-α-methylaspartate, L-α-methylcysteine, L-α-methylglutamine, L-α-methylhistidine, L-α-methylisoleucine, L-α- UM-41715.601 methylleucine, L-α-methylmethionine, L-α-methylnorvaline, L-α-methylphenylalanine, L-α- methylserine, L-α-methyltryptophan, L-α-methylvaline, N-(N-(2,2-diphenylethyl) carbamylmethylglycine, 1-carboxy-1-(2,2-diphenyl-ethylamino) cyclopropane, 4- hydroxyproline, ornithine, 2-aminobenzoyl (anthraniloyl), D-cyclohexylalanine, 4-phenyl- phenylalanine, L-citrulline, α-cyclohexylglycine, L-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, L-thiazolidine-4-carboxylic acid, L-homotyrosine, L-2-furylalanine, L-histidine (3- methyl), N-(3-guanidinopropyl)glycine, O-methyl-L-tyrosine, O-glycan-serine, meta-tyrosine, nor-tyrosine, L-N,N′,N″-trimethyllysine, homolysine, norlysine, N-glycan asparagine, 7- hydroxy-1,2,3,4-tetrahydro-4-fluorophenylalanine, 4-methylphenylalanine, bis-(2-picolyl)amine, pentafluorophenylalanine, indoline-2-carboxylic acid, 2-aminobenzoic acid, 3-amino-2- naphthoic acid, asymmetric dimethylarginine, L-tetrahydroisoquinoline-1-carboxylic acid, D- tetrahydroisoquinoline-1-carboxylic acid, 1-amino-cyclohexane acetic acid, D / L-allylglycine, 4- aminobenzoic acid, 1-amino-cyclobutane carboxylic acid, 2 or 3 or 4-aminocyclohexane carboxylic acid, 1-amino-1-cyclopentane carboxylic acid, 1-aminoindane-1-carboxylic acid, 4- amino-pyrrolidine-2-carboxylic acid, 2-aminotetraline-2-carboxylic acid, azetidine-3-carboxylic acid, 4-benzyl-pyrolidine-2-carboxylic acid, tert-butylglycine, b-(benzothiazolyl-2-yl)-alanine, b-cyclopropyl alanine, 5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid, (2R,4S)4- hydroxypiperidine-2-carboxylic acid, (2S,4S) and (2S,4R)-4-(2-naphthylmethoxy)-pyrolidine-2- carboxylic acid, (2S,4S) and (2S,4R)4-phenoxy-pyrrolidine-2-carboxylic acid, (2R,5S)and(2S,5R)-5-phenyl-pyrrolidine-2-carboxylic acid, (2S,4S)-4-amino-1-benzoyl- pyrrolidine-2-carboxylic acid, t-butylalanine, (2S,5R)-5-phenyl-pyrrolidine-2-carboxylic acid, 1- aminomethyl-cyclohexane-acetic acid, 3,5-bis-(2-amino)ethoxy-benzoic acid, 3,5-diamino- benzoic acid, 2-methylamino-benzoic acid, N-methylanthranylic acid, L-N-methylalanine, L-N- methylarginine, L-N-methylasparagine, L-N-methylaspartic acid, L-N-methylcysteine, L-N- methylglutamine, L-N-methylglutamic acid, L-N-methylhistidine, L-N-methylisoleucine, L-N- methyllysine, L-N-methylnorleucine, L-N-methylornithine, L-N-methylthreonine, L-N- methyltyrosine, L-N-methylvaline, L-N-methyl-t-butylglycine, L-norvaline, α-methyl-γ- aminobutyrate, 4,4′-biphenylalanine, α-methylcylcopentylalanine, α-methyl-α-napthylalanine, α- methylpenicillamine, N-(4-aminobutyl)glycine, N-(2-aminoethyl)glycine, N-(3- aminopropyl)glycine, N-amino-α-methylbutyrate, α-napthylalanine, N-benzylglycine, N-(2- carbamylethyl)glycine, N-(carbamylmethyl)glycine, N-(2-carboxyethyl)glycine, N- (carboxymethyl)glycine, N-cyclobutylglycine, N-cyclodecylglycine, N-cycloheptylglycine, N- cyclohexylglycine, N-cyclodecylglycine, N-cylcododecylglycine, N-cyclooctylglycine, N- cyclopropylglycine, N-cycloundecylglycine, N-(2,2-diphenylethyl)glycine, N-(3,3- UM-41715.601 diphenylpropyl)glycine, N-(3-guanidinopropyl)glycine, N-(1-hydroxyethyl)glycine, N- (hydroxyethyl))glycine, N-(imidazolylethyl))glycine, N-(3-indolylyethyl)glycine, N-methyl-γ- aminobutyrate, D-N-methylmethionine, N-methylcyclopentylalanine, D-N-methylphenylalanine, D-N-methylproline, D-N-methylthreonine, N-(1-methylethyl)glycine, N-methyl-napthylalanine, N-methylpenicillamine, N-(p-hydroxyphenyl)glycine, N-(thiomethyl)glycine, penicillamine, L- α-methylalanine, L-α-methylasparagine, L-α-methyl-t-butylglycine, L-methylethylglycine, L-α- methylglutamate, L-α-methylhomophenylalanine, N-(2-methylthioethyl)glycine, L-α- methyllysine, L-α-methylnorleucine, L-α-methylornithine, L-α-methylproline, L-α- methylthreonine, L-α-methyltyrosine, L-N-methyl-homophenylalanine, N-(N-(3,3- diphenylpropyl) carbamylmethylglycine, L-pyroglutamic acid, D-pyroglutamic acid, O-methyl- L-serine, O-methyl-L-homoserine, 5-hydroxylysine, α-carboxyglutamate, phenylglycine, L- pipecolic acid (homoproline), L-homoleucine, L-lysine (dimethyl), L-2-naphthylalanine, L- dimethyldopa or L-dimethoxy-phenylalanine, L-3-pyridylalanine, L-histidine (benzoyloxymethyl), N-cycloheptylglycine, L-diphenylalanine, O-methyl-L-homotyrosine, L-β- homolysine, O-glycan-threoine, Ortho-tyrosine, L-N,N′-dimethyllysine, L-homoarginine, neotryptophan, 3-benzothienylalanine, isoquinoline-3-carboxylic acid, diaminopropionic acid, homocysteine, 3,4-dimethoxyphenylalanine, 4-chlorophenylalanine, L-1,2,3,4- tetrahydronorharman-3-carboxylic acid, adamantylalanine, symmetrical dimethylarginine, 3- carboxythiomorpholine, D-1,2,3,4-tetrahydronorharman-3-carboxylic acid, 3-aminobenzoic acid, 3-amino-1-carboxymethyl-pyridin-2-one, 1-amino-1-cyclohexane carboxylic acid, 2- aminocyclopentane carboxylic acid, 1-amino-1-cyclopropane carboxylic acid, 2-aminoindane-2- carboxylic acid, 4-amino-tetrahydrothiopyran-4-carboxylic acid, azetidine-2-carboxylic acid, b- (12unction1212ole-2-yl)-alanine, neopentylglycine, 2-carboxymethyl piperidine, b-cyclobutyl alanine, allylglycine, diaminopropionic acid, homo-cyclohexyl alanine, (2S,4R)- 4- hydroxypiperidine-2-carboxylic acid, octahydroindole-2-carboxylic acid, (2S,4R) and (2S,4R)- 4-(2-naphthyl), pyrrolidine-2-carboxylic acid, nipecotic acid, (2S,4R)and (2S,4S)-4-(4- phenylbenzyl) pyrrolidine-2-carboxylic acid, (3S)-1-pyrrolidine-3-carboxylic acid, (2S,4S)-4- tritylmercapto-pyrrolidine-2-carboxylic acid, (2S,4S)-4-mercaptoproline, t-butylglycine, N,N- bis(3-aminopropyl)glycine, 1-amino-cyclohexane-1-carboxylic acid, N-mercaptoethylglycine, and selenocysteine. In some embodiments, amino acid residues may be charged or polar. Charged amino acids include alanine, lysine, aspartic acid, or glutamic acid, or non-naturally occurring analogs thereof. Polar amino acids include glutamine, asparagine, histidine, serine, threonine, tyrosine, methionine, or tryptophan, or non-naturally occurring analogs thereof. It is UM-41715.601 specifically contemplated that in some embodiments, a terminal amino group in the amino acid may be an amido group or a carbamate group. “Percent (%) sequence identity” with respect to a reference polynucleotide or polypeptide sequence is defined as the percentage of nucleic acids or amino acids in a candidate sequence that are identical to the nucleic acids or amino acids in the reference polynucleotide or polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent nucleic acid or amino acid sequence identity can be achieved in various ways that are within the capabilities of one of skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, or Megalign software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. For example, percent sequence identity values may be generated using the sequence comparison computer program BLAST. As an illustration, the percent sequence identity of a given nucleic acid or amino acid sequence, A, to, with, or against a given nucleic acid or amino acid sequence, B, (which can alternatively be phrased as a given nucleic acid or amino acid sequence, A that has a certain percent sequence identity to, with, or against a given nucleic acid or amino acid sequence, B) is calculated as follows: 100 multiplied by (the fraction X / Y) where X is the number of nucleotides or amino acids scored as identical matches by a sequence alignment program (e.g., BLAST) in that program’s alignment of A and B, and where Y is the total number of nucleic acids in B. It will be appreciated that where the length of nucleic acid or amino acid sequence A is not equal to the length of nucleic acid or amino acid sequence B, the percent sequence identity of A to B will not equal the percent sequence identity of B to A. The term “protein” refers to polymers of amino acids (e.g., naturally occurring amino acids and non-natural amino acids) of any length. The terms also encompass an amino acid polymer that has been modified; for example, disulfide bond formation, glycosylation, acetylation, phosphorylation, lipidation, or conjugation with a labeling component. As used herein, the term “peptide” refers to a polymer in which the monomers are amino acids covalently attached together through amide bonds. Peptides are two or often more amino acids monomers long. By “pharmaceutical composition” is meant any composition that contains a peptide that is suitable for administration to a subject. Any formulation can be prepared by well-known and accepted methods in the art. See, for example, Remington: The Science and Practice of UM-41715.601 Pharmacy (21sted.), ed. A.R. Gennaro, Lippincott Williams & Wilkins, 2005, and Encyclopedia of Pharmaceutical Technology, ed. J. Swarbrick, Informa Healthcare, 2006, each of which is hereby incorporated by reference. By “pharmaceutically acceptable diluent, excipient, carrier, or adjuvant” is meant a diluent, excipient, carrier, or adjuvant which is physiologically acceptable to the subject while retaining the therapeutic properties of the pharmaceutical composition with which it is administered. As used herein, the term “sample” is used in its broadest sense. In one sense, it is meant to include a specimen or culture obtained from any source, as well as biological and environmental samples. Biological samples may be obtained from animals (including humans) and encompass fluids, solids, tissues, and gases. Biological samples include blood products, such as plasma, serum and the like. Environmental samples include environmental material such as surface matter, soil, water, crystals, and industrial samples. Such examples are not however to be construed as limiting the sample types applicable to the present invention. As used herein, the term “subject” refers to any animal (e.g., a mammal), including, but not limited to, humans, non-human primates, rodents, and the like, which is to be the recipient of a particular treatment. Typically, the terms “subject” and “patient” are used interchangeably herein in reference to a human subject. As used herein, the terms “synthetic HDL,” “sHDL,” “reconstituted HDL”, and “rHDL” refer to a particle structurally analogous to native HDL, composed of a lipid or lipids in association with at least one of the proteins of HDL, preferably ApoA-I, or a mimetic thereof. Typically, the components of sHDL may be derived from blood or produced by recombinant technology. By “therapeutically effective amount” is meant the amount of a composition administered to improve, inhibit, or ameliorate a condition of a subject, or a symptom of a disorder or disease, e.g., celiac disease, in a clinically relevant manner. Any improvement in the subject is considered sufficient to achieve treatment. Preferably, an amount sufficient to treat is an amount that reduces, inhibits, or prevents the occurrence or one or more symptoms of the disease or disorder or is an amount that reduces the severity of, or the length of time during which a subject suffers from one or more symptoms of the disease or disorder (e.g., by at least about 10%, about 20%, or about 30%, more preferably by at least about 50%, about 60%, or about 70%, and most preferably by at least about 80%, about 90%, about 95%, about 99%, or more, relative to a control subject that is not treated with a composition described herein). An effective amount of the pharmaceutical composition used to practice the methods described UM-41715.601 herein varies depending upon the manner of administration and the age, body weight, and general health of the subject being treated. A physician or researcher can decide the appropriate amount and dosage regimen. As used herein, the term “solvent” refers to a medium in which a reaction is conducted. Solvents may be liquid but are not limited to liquid form. Solvent categories include but are not limited to nonpolar, polar, protic, and aprotic. DETAILED DESCRIPTION OF THE INVENTION Experiments conducted during the course of developing embodiments for the present invention resulted in the development of a new strategy for attaching negatively or positively charged amino acids either at the C or N terminus to increase the aqueous solubility of peptides and to improve the manufacturability of peptide-loaded sHDL NDs. Such experiments demonstrated that for peptides with a high isoelectric point (pI), the addition of negatively charged amino acids (such as aspartic acid or glutamic acid) to the peptide sequence leads to the conversion of the net charge from a positive to a negative value at pH 7. Such charge conversion allows for efficient and robust loading of peptide-lipid conjugates onto NDs, resulting in homogeneous and uniform peptide-loaded NDs. Thus, the addition of negatively or positively charged amino acids either at C or N terminus of peptides offers a universal strategy for improving the incorporation of peptides to NDs and for improving the manufacturing of peptide- NDs products. Additionally, our approach demonstrates versatility in using peptides with cysteine residues not only at the N-terminus but also at the C-terminus or non-terminal positions to obtain peptide-loaded sHDL NDs. Overall, embodiments described herein pertain to a new composition of matter that improves the incorporation of various peptides into NDs and the manufacturing of peptide-NDs products. Also, this approach may be generally applicable for incorporating various peptides into other nanoparticles and polymers. Accordingly, in certain embodiments, the present invention provides compositions comprising sHDL nanoparticle. In some embodiments, the sHDL nanoparticles comprising a phospholipid; an apoplipoprotein mimetic; a thiol-reactive lipid; and a peptide comprising a linker moiety connected with a payload moiety, wherein the linker comprises either: [cysteine (C) and optionally one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S)] or [D-D or D-D-D if the payload includes a C amino acid], the payload comprises a polypeptide that is 5 to 35 amino acids in length and has a net positive charge at a pH of 7 to 12, and the peptide comprises a net negative charge at a pH of 7 and an UM-41715.601 isoelectric point of 0.4 to 12; and wherein the peptide is covalently attached to the thiol-reactive lipid by way of the linker. In some embodiments, the peptide is covalently attached to the thiol-reactive lipid by way of the Cys. In some embodiments, the peptide is covalently attached to the thiol-reactive lipid by way of the carboxy terminus of the Cys. In some embodiments, the peptide is covalently attached to the thiol-reactive lipid by way of the amino terminus of the Cys. In some embodiments, the peptide is covalently attached to the thiol-reactive lipid by way of a non- terminal position terminus of the Cys. In some embodiments, if the payload includes a C amino acid, the peptide is covalently attached to the thiol-reactive lipid by way of the linker, wherein the linker comprises D-D or D- D-D. In some embodiments, the peptide comprises the formula: [linker]-[payload] or [payload]-[linker]. In some embodiments, the payload has a net positive charge at a pH of 7 to 12. In some embodiments, the payload has a net zero charge at a pH of 7 to 12. In some embodiments, the payload has a net negative charge at a pH of 7 to 12. In some embodiments, the peptide has a charge of less than -0.1. In some embodiments, the peptide has a charge ranging from -0.1 to -5.0. In some embodiments, the peptide comprises an isoelectric point of 3.7 to 12. In some embodiments, the peptide comprises an isoelectric point of 0.62 to 9.78. In some embodiments, the linker sequence is C. In some embodiments, the linker sequence is DDCDD. In some embodiments, the linker sequence is DD or DDD if the payload includes a C amino acid. In some embodiments, the one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S) comprises a peptide dimer. In some embodiments, the peptide dimer is selected from DD, SE, SD, and EE. In some embodiments, the one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S) comprises a peptide trimer. In some embodiments, the peptide trimer is selected from DDD, EEE, and KEE. In some embodiments, the one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S) comprises a peptide 4-mer. In some embodiments, the peptide 4-mer is selected from DDDD (SEQ ID NO:762) and EEEE (SEQ ID NO:763). UM-41715.601 In some embodiments, the payload has a charge of greater than 0.1 at pH 7. In some embodiments, the payload has a charge ranging from 0.1 to 5.0. In some embodiments, the payload is a polypeptide that is 12 to 35 amino acids in length. In some embodiments, the payload is selected from GWYRSPFSRVVHL (SEQ ID NO:764), NTWTTSQSIAFPSK (SEQ ID NO:765), KVAPVWVRMME (SEQ ID NO:766), KYNKANAFL (SEQ ID NO:767), and ASFEAQGALANIAVDKA (SEQ ID NO:768). In some embodiments, the apolipoprotein mimetic is an ApoA-I mimetic, having a sequence of any of SEQ ID NOs: 1-336 and WDRVKDLATVYVDVLKDSGRDYVSQF (SEQ ID NO:341), LKLLDNWDSVTSTFSKLREOL (SEQ ID NO:342), PVTOEFWDNLEKETEGLROEMS (SEQ ID NO:343), KDLEEVKAKVQ (SEQ ID NO: 344), KDLEEVKAKVO (SEQ ID NO: 345), PYLDDFQKKWQEEMELYRQKVE (SEQ ID NO: 346), PLRAELQEGARQKLHELOEKLS (SEQ ID NO: 347), PLGEEMRDRARAHVDALRTHLA (SEQ ID NO: 348), PYSDELRQRLAARLEALKENGG (SEQ ID NO: 349), ARLAEYHAKATEHLSTLSEKAK (SEQ ID NO: 350), PALEDLROGLL (SEQ ID NO: 351), PVLESFKVSFLSALEEYTKKLN (SEQ ID NO:352), PVLESFVSFLSALEEYTKKLN (SEQ ID NO:353), PVLESFKVSFLSALEEYTKKLN (SEQ ID NO:352), TVLLLTICSLEGALVRRQAKEPCV (SEQ ID NO: 354) QTVTDYGKDLME (SEQ ID NO:355), KVKSPELOAEAKSYFEKSKE (SEQ ID NO:356), VLTLALVAVAGARAEVSADOVATV (SEQ ID NO:357), NNAKEAVEHLOKSELTOOLNAL (SEQ ID NO:358), LPVLVWLSIVLEGPAPAOGTPDVSS (SEQ ID NO:359), LPVLVVVLSIVLEGPAPAQGTPDVSS (SEQ ID NO:360), ALDKLKEFGNTLEDKARELIS (SEQ ID NO: 361), VVALLALLASARASEAEDASLL (SEQ ID NO:362), HLRKLRKRLLRDADDLQKRLAVYOA (SEQ ID NO:363), AQAWGERLRARMEEMGSRTRDR (SEQ ID NO:364), LDEVKEQVAEVRAKLEEQAQ (SEQ ID NO:365), DWLKAFYDKVAEKLKEAF (SEQ ID NO:236), DWLKAFYDKVAEKLKEAFPDWAKAAYDKAAEKAKEAA (SEQ ID NO:366), PVLDLFRELLNELLEALKQKL (SEQ ID NO:367), PVLDLFRELLNELLEALKQKLA (SEQ ID NO:368), PVLDLFRELLNELLEALKQKLK (SEQ ID NO:4), PVLDLFRELLNELLEALKQKLA (SEQ ID NO:369), PVLDLFRELLNELLEALKKLLK (SEQ ID NO:370), PVLDLFRELLNELLEALKKLLA (SEQ ID NO:371), UM-41715.601 PLLDLFRELLNELLEALKKLLA (SEQ ID NO:372), and EVRSKLEEWFAAFREFAEEFLARLKS (SEQ ID NO: 373). In some embodiments, the apolipoprotein mimetic has the sequence PVLDLFRELLNELLEALKQKLK (SEQ ID NO: 4). In some embodiments, the thiol-reactive lipid is selected from dioleoyl-sn-glycero-3- phosphoethanolamine-N-[3-(2-pyridyldithio) propionate] (DOPE-PDP), 1,2-di-(9Z- octadecenoyl)-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidophenyl)butyramide], 1,2- dihexadecanoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidophenyl)butyramide], 1,2- dihexadecanoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidomethyl)cyclohexane- carboxamide], 1,2-Dioleoyl-sn–glycero-3-phosphoethanolamine-maleimide (DOPE-Mal), and 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine-N-[4-(p- maleimidomethyl)cyclohexane-carboxamide]. In some embodiments, the thiol-reactive lipid is DOPE-PDP. In certain embodiments, the present invention provides methods for treating, preventing and / or attenuating a disorder comprising administering to a subject (e.g., a human subject suffering from or at risk of suffering a disease or medical condition) a composition as described herein. Such methods are not limited to treating a particular disorder. In some embodiments, the disorder is an autoimmune disorder. Such methods are not limited to treating a particular autoimmune disorder. Examples of autoimmune disorders include, but are not limited to, multiple sclerosis (MS), celiac disease, rheumatoid arthritis, primary biliary cholangitis, primary sclerosing cholangitis, MOG antibody disease, diabetes (e.g., type 1 diabetes mellitus), autoimmune diseases of the thyroid (e.g., Hashimoto’s thyroiditis, Graves’ disease), thyroid-associated ophthalmopathy and dermopathy, hypoparathyroidism, Addison’s disease, premature ovarian failure, autoimmune hypophysitis, pituitary autoimmune disease, immunogastritis, pernicious angemis, celiac disease, vitiligo, myasthenia gravis, pemphigus vulgaris and variants, bullous pemphigoid, dermatitis herpetiformis Duhring, epidermolysis bullosa acquisita, systemic sclerosis, mixed connective tissue disease, Sjogren’s syndrome, systemic lupus erythematosus, Goodpasture's syndrome, rheumatic heart disease, autoimmune polyglandular syndrome type 1, Aicardi–Goutières syndrome, Acute pancreatitis Age-dependent macular degeneration, Alcoholic liver disease, Liver fibrosis, Metastasis, Myocardial infarction, Nonalcoholic steatohepatitis (NASH), UM-41715.601 Parkinson’s disease, Polyarthritis / fetal and neonatal anemia, Sepsis, and inflammatory bowel disease. In some embodiments, the disorder is a transplantation related disorder. In some embodiments, the disorder is one or more allergies. In some embodiments, the disorder is a respiratory condition (e.g., asthma). In some embodiments, the disorder is graft-versus-host- disease (GvHD). In some embodiments, such methods for treating or preventing autoimmune disorders further comprise co-administering (e.g., simultaneously or at different times) additional therapeutic agents. Examples of such therapeutic agents include, but are not limited to, disease- modifying antirheumatic drugs (e.g., leflunomide, methotrexate, sulfasalazine, hydroxychloroquine), biologic agents (e.g., rituximab, infliximab, etanercept, adalimumab, golimumab), nonsteroidal anti-inflammatory drugs (e.g., ibuprofen, celecoxib, ketoprofen, naproxen, piroxicam, diclofenac), analgesics (e.g., acetaminophen, tramadol), immunomodulators (e.g., anakinra, abatacept), glucocorticoids (e.g., prednisone, methylprednisone), TNF-α inhibitors (e.g., adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), IL-1 inhibitors, and metalloprotease inhibitors. In some embodiments, the therapeutic agents include, but are not limited to, infliximab, adalimumab, etanercept, or parenteral gold or oral gold. In some instances, the therapeutic agent is an immunomodulatory agent or immunosuppressant (e.g., statins; mTOR inhibitors, such as rapamycin or a rapamycin analog; TGF-β signaling agents; TGF-β receptor agonists; histone deacetylase inhibitors, such as Trichostatin A; corticosteroids; inhibitors of mitochondrial function, such as rotenone; P38 inhibitors; NF-κβ inhibitors, such as 6Bio, Dexamethasone, TCPA-1, IKK VII; adenosine receptor agonists; prostaglandin E2 agonists (PGE2), such as Misoprostol; phosphodiesterase inhibitors, such as phosphodiesterase 4 inhibitor (PDE4), such as Rolipram; proteasome inhibitors; kinase inhibitors; G-protein coupled receptor agonists; G-protein coupled receptor antagonists; glucocorticoids; retinoids; cytokine inhibitors; cytokine receptor inhibitors; cytokine receptor activators; peroxisome proliferator-activated receptor antagonists; peroxisome proliferator-activated receptor agonists; histone deacetylase inhibitors; calcineurin inhibitors; phosphatase inhibitors; PI3 KB inhibitors, such as TGX-221; autophagy inhibitors, such as 3- Methyladenine; aryl hydrocarbon receptor inhibitors; proteasome inhibitor I (PSI); and oxidized ATPs, such as P2X receptor blockers. Immunosuppressants also include IDO, vitamin D3, cyclosporins, such as cyclosporine A, aryl hydrocarbon receptor inhibitors, resveratrol, azathiopurine (Aza), 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), FK506, sanglifehrin A, salmeterol, mycophenolate mofetil (MMF), aspirin and other COX inhibitors, niflumic acid, UM-41715.601 estriol, triptolide; OPN-305, OPN-401; Eritoran (E5564); TAK-242; Cpn10; NI-0101; 1A6; AV411; IRS-954 (DV-1079); IMO-3100; CPG-52363; CPG-52364; OPN-305; ATNC05; NI- 0101; IMO-8400; Hydroxychloroquine; CU-CPT22; C29; Ortho-vanillin; SSL3 protein; OPN- 305; 5 SsnB; Vizantin; (+)-N-phenethylnoroxymorphone; VB3323; Monosaccharide 3; (+)- Naltrexone and (+)-naloxone; HT52; HTB2; Compound 4a; CNTO2424; TH1020; INH-ODN; E6446; AT791; CpG ODN 2088; ODN TTAGGG; COV08-0064; 2R9; GpG oligonucleotides; 2-aminopurine; Amlexanox; Bay11-7082; BX795; CH-223191; Chloroquine; CLI-095; CU- CPT9a; Cyclosporin A; CTY387; Gefitnib; Glybenclamide; H-89; H-131; Isoliquiritigenin; MCC950; MRT67307; OxPAPC; Parthenolide; Pepinh-MYD; Pepinh-TRIF; Polymyxin B; R406; RU.521; VX-765; YM201636; Z-VAD-FMK; and AHR-specific ligands; including but not limited to 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD); tryptamine (TA); and 6 formylindolo[3,2 b]carbazole (FICZ)). In particular embodiments, the immunosuppressant is fingolimod; rapamycin; 2-(1’H-indole-3’-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) or related ligands; Trichostatin A; and / or Suberoylanilide hydroxamic acid (SAHA). The present invention is not limited to specific types or kinds of nanoparticles associated with (e.g., complexed, conjugated, encapsulated, absorbed, adsorbed, admixed) or not associated with peptides as described herein. Examples of nanoparticles include, but are not limited to, fullerenes (a.k.a. C60, C70, C76, C80, C84), endohedral metallofullerenes (EMI’s) buckyballs, which contain additional atoms, ions, or clusters inside their fullerene cage), trimetallic nitride templated endohedral metallofullerenes (TNT EMEs, high-symmetry four-atom molecular cluster endohedrals, which are formed in a trimetallic nitride template within the carbon cage), single-walled and multi- walled carbon nanotubes, branched and dendritic carbon nanotubes, gold nanorods, silver nanorods, single-walled and multi-walled boron / nitrate nanotubes, carbon nanotube peapods (nanotubes with internal metallo-fullerenes and / or other internal chemical structures), carbon nanohorns, carbon nanohorn peapods, liposomes, nanoshells, dendrimers, quantum dots, superparamagnetic nanoparticles, nanorods, and cellulose nanoparticles. The particle embodiment can also include microparticles with the capability to enhance effectiveness or selectivity. Other non-limiting exemplary nanoparticles include glass and polymer micro- and nano-spheres, biodegradable PLGA micro- and nano-spheres, gold, silver, carbon, and iron nanoparticles. In some embodiments, the nanoparticle is a modified micelle. In these embodiments, the modified micelle comprises polyol polymers modified to contain a hydrophobic polymer block. The term “hydrophobic polymer block” as used in the present disclosure indicates a segment of UM-41715.601 the polymer that on its own would be hydrophobic. The term “micelle” as used herein refers to an aggregate of molecules dispersed in a liquid. A typical micelle in aqueous solution forms an aggregate with the hydrophilic “head” regions in contact with surrounding solvent, sequestering the hydrophobic single tail regions in the micelle centre. In some embodiments the head region may be, for example, a surface region of the polyol polymer while the tail region may be, for example, the hydrophobic polymer block region of the polyol polymer. The invention further encompasses use of particles on the micrometer scale in addition to the nanometer scale. Where microparticles are used, it is preferred that they are relatively small, on the order of 1-50 micrometers. For ease of discussion, the use herein of “nanoparticles” encompasses true nanoparticles (sizes of from about 1 nm to about 1000 nm), microparticles (e.g., from about 1 micrometer to about 50 micrometers), or both. Examples of nanoparticles include, by way of example and without limitation, paramagnetic nanoparticles, superparamagnetic nanoparticles, metal nanoparticles, fullerene-like materials, inorganic nanotubes, dendrimers, dendrimers with covalently attached metal chelates, nanofibers, nanohorns, nano-onions, nanorods, nanoropes, and quantum dots. In some embodiments, a nanoparticle is a metal nanoparticle (for example, a nanoparticle of gold, palladium, platinum, silver, copper, nickel, cobalt, iridium, or an alloy of two or more thereof). Nanoparticles can include a core or a core and a shell, as in core- shell nanoparticles. In some embodiments, the nanoparticles are sHDL nanoparticles. Generally, sHDL nanoparticles are composed of a mixture of HDL apolipoprotein and an amphipathic lipid. The present invention is not limited to use of a particular type or kind of HDL apolipoprotein. HDL apolipoproteins include, for example apolipoprotein A-I (apo A-I), apolipoprotein A-II (apo A-II), apolipoprotein A4 (apo A4), apolipoprotein Cs (apo Cs), apolipoprotein M (apo M), and apolipoprotein E (apo E). In some embodiments, the HDL apolipoprotein is selected from preproapoliprotein, preproApoA-I, proApoA-I, AρoA-I, preproApoA-II, proApoA-II, ApoA-II, apolipoprotein A-II xxx (apo A-II-xxx), preproApoA-lV, proApoA-lV, ApoA-IV, ApoA-V, preproApoE, proApoE, ApoE, preproApoA-lMilano, ρroApoA-Imilano, ApoA-lMilano, ρreproApoA-Iparis, proApoA-Iparis, ApoA-Iparis, and peptide mimetics of these proteins mixtures thereof. Preferably, the carrier particles are composed of ApoA-I or ApoA-II, however the use of other lipoproteins including apolipoprotein A4, apolipoprotein Cs or apolipoprotein E may be used alone or in combination to formulate carrier particle mixtures for delivery of therapeutic agents. In some embodiments, mimetics of such HDL apolipoproteins are used. UM-41715.601 ApoA-I is synthesized by the liver and small intestine as preproapolipoprotein which is secreted as a proprotein that is rapidly cleaved to generate a mature polypeptide having 243 amino acid residues. ApoA-I consists mainly of 6 to 8 different 22 amino acid repeats, and 2 different 11 amino acid repeats, each of which has the helical wheel signature of an amphipathic α helix, spaced by a linker moiety which is often proline, and, in some cases, consists of a stretch made up of several residues. ApoA-I forms three types of stable complexes with lipids: small, lipid-poor complexes referred to as pre-beta-1 HDL; flattened discoidal particles containing polar lipids (phospholipid and cholesterol) referred to as pre-beta-2 HDL; and spherical particles containing both polar and nonpolar lipids, referred to as spherical or mature HDL (HDL3 and HDL2). Most HDL in the circulating population contain both ApoA-I and ApoA-II (the second major HDL protein). In some embodiments, ApoA-I agonists or mimetics are provided. In some embodiments, such ApoA-I mimetics are capable of forming amphipathic α-helices that mimic the activity of ApoA-I, and have specific activities approaching or exceeding that of the native molecule. In some, the ApoA-I mimetics are peptides or peptide analogues that: form amphipathic helices (in the presence of lipids), bind lipids, form pre-β-like or HDL-like complexes, activate lecithin: cholesterol acyltransferase (LCAT), increase serum levels of HDL fractions, and promote cholesterol efflux. The present invention is not limited to use of a particular ApoA-I mimetic. In some embodiments, any of the ApoA-I mimetics described in Srinivasa, et al., 2014 Curr. Opinion Lipidology Vol.25(4): 304-308 are utilized. In some embodiments, any of the ApoA-I mimetics described in U.S. Patent Application Publication Nos.20110046056 and 20130231459 are utilized. In some embodiments, the “22A” ApoA-I mimetic is used (PVLDLFRELLNELLEALKQKLK) (SEQ ID NO: 4) (see, e.g., U.S. Patent No.7,566,695). In some embodiments, any of the following ApoA-I mimetics shown in Table 1 as described in U.S. Patent No.7,566,695 are utilized: Table 1. ApoA-I mimetics SEQ ID NO AMINO ACID SEQUENCE UM-41715.601 SEQ ID NO AMINO ACID SEQUENCE (SEQ ID NO:6) PVLDLFRELLNEXLEALKQKLK UM-41715.601 SEQ ID NO AMINO ACID SEQUENCE (SEQ ID NO:47) ~VLDLFRELLNEGLEALKQKLK UM-41715.601 SEQ ID NO AMINO ACID SEQUENCE (SEQ ID NO:88) PVLDKFRELLNEXLEALKQKLK UM-41715.601 SEQ ID NO AMINO ACID SEQUENCE (SEQ ID NO:129) PVLELFNDLLRELLEALQKKLK UM-41715.601 SEQ ID NO AMINO ACID SEQUENCE (SEQ ID NO:170) PVLELFENLLEOLLDALQOOLO UM-41715.601 SEQ ID NO AMINO ACID SEQUENCE (SEQ ID NO:211) PVLDLFRELLEELOQOLO* UM-41715.601 SEQ ID NO AMINO ACID SEQUENCE (SEQ ID NO:252) PVLDLFRELLEALKQK* * indicates ates peptides that are N-terminal dansylated; sp indicates peptides that eXhibited solubility problems under the experimental conditions; X is Aib; Z is Nal; O is Orn; and ˜ indicates deleted amino acids. In some embodiments, an ApoA-I mimetic having the following sequence as described in U.S. Patent No.6,743,778 is utilized: Asp Trp Leu Lys Ala Phe Tyr Asp Lys Val Ala Glu Lys Leu Lys Glu Ala Phe (SEQ ID NO: 255). In some embodiments, any of the following ApoA-I mimetics shown in Table 2 as described in U.S. Patent Application Publication No.2003 / 0171277 are utilized: Table 2. ApoA-I mimetics SEQ ID NO AMINO ACID SEQUENCE UM-41715.601 SEQ ID NO AMINO ACID SEQUENCE (SEQ ID NO:275) Ac-E-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-F-F-NH2 2 UM-41715.601 SEQ ID NO AMINO ACID SEQUENCE (SEQ ID NO:308) Ac-D-K-W-K-A-V-Y-D-K-F-A-E-A-F-K-E-F-L-NH2 In some embodiments, an Apo A-I mimetic having the following sequence as described in U.S. Patent Application Publication No.2006 / 0069030 is utilized: F-A-E-K-F-K-E-A-V-K- D-Y-F-A-K-F-W-D (SEQ ID NO:333). In some embodiments, an Apo A-I mimetic having the following sequence as described in U.S. Patent Application Publication No.2009 / 0081293 is utilized: DWFKAFYDKVAEKFKEAF (SEQ ID NO: 334); DWLKAFYDKVAEKLKEAF (SEQ ID NO: 335); PALEDLRQGLLPVLESFKVFLSALEEYTKKLNTQ (SEQ ID NO: 336). UM-41715.601 In some embodiments, an Apo A-I mimetic having one of the following sequences is utilized: WDRVKDLATVYVDVLKDSGRDYVSQF (SEQ ID NO:341), LKLLDNWDSVTSTFSKLREOL (SEQ ID NO:342), PVTOEFWDNLEKETEGLROEMS (SEQ ID NO:343), KDLEEVKAKVQ (SEQ ID NO: 344), KDLEEVKAKVO (SEQ ID NO: 345), PYLDDFQKKWQEEMELYRQKVE (SEQ ID NO: 346), PLRAELQEGARQKLHELOEKLS (SEQ ID NO: 347), PLGEEMRDRARAHVDALRTHLA (SEQ ID NO: 348), PYSDELRQRLAARLEALKENGG (SEQ ID NO: 349), ARLAEYHAKATEHLSTLSEKAK (SEQ ID NO: 350), PALEDLROGLL (SEQ ID NO: 351), PVLESFKVSFLSALEEYTKKLN (SEQ ID NO:352), PVLESFVSFLSALEEYTKKLN (SEQ ID NO:353), PVLESFKVSFLSALEEYTKKLN (SEQ ID NO:352), TVLLLTICSLEGALVRRQAKEPCV (SEQ ID NO: 354) QTVTDYGKDLME (SEQ ID NO:355), KVKSPELOAEAKSYFEKSKE (SEQ ID NO:356), VLTLALVAVAGARAEVSADOVATV (SEQ ID NO:357), NNAKEAVEHLOKSELTOOLNAL (SEQ ID NO:358), LPVLVWLSIVLEGPAPAOGTPDVSS (SEQ ID NO:359), LPVLVVVLSIVLEGPAPAQGTPDVSS (SEQ ID NO:360), ALDKLKEFGNTLEDKARELIS (SEQ ID NO: 361), VVALLALLASARASEAEDASLL (SEQ ID NO:362), HLRKLRKRLLRDADDLQKRLAVYOA (SEQ ID NO:363), AQAWGERLRARMEEMGSRTRDR (SEQ ID NO:364), LDEVKEQVAEVRAKLEEQAQ (SEQ ID NO:365), DWLKAFYDKVAEKLKEAF (SEQ ID NO:236), DWLKAFYDKVAEKLKEAFPDWAKAAYDKAAEKAKEAA (SEQ ID NO:366), PVLDLFRELLNELLEALKQKL (SEQ ID NO:367), PVLDLFRELLNELLEALKQKLA (SEQ ID NO:368), PVLDLFRELLNELLEALKQKLK (SEQ ID NO:4), PVLDLFRELLNELLEALKQKLA (SEQ ID NO:369), PVLDLFRELLNELLEALKKLLK (SEQ ID NO:370), PVLDLFRELLNELLEALKKLLA (SEQ ID NO:371), PLLDLFRELLNELLEALKKLLA (SEQ ID NO:372), and EVRSKLEEWFAAFREFAEEFLARLKS (SEQ ID NO: 373). Amphipathic lipids include, for example, any lipid molecule which has both a hydrophobic and a hydrophilic moiety. Examples include phospholipids or glycolipids. Examples of phospholipids which may be used in the sHDL-peptide nanoparticles include but are not limited to 1,2-dilauroyl-sn-glycero-3-phosphocholine; 1,2-dimyristoyl-sn-glycero-3- phosphocholine; 1,2-dipalmitoyl-sn-glycero-3-phosphocholine; 1,2-distearoyl-sn-glycero-3- phosphocholine; 1,2-diarachidoyl-sn-glycero-3-phosphocholine; 1,2-dibehenoyl-sn-glycero-3- phosphocholine; 1,2-dilignoceroyl-sn-glycero-3-phosphocholine; 1,2-dimyristoleoyl-sn-glycero- UM-41715.601 3-phosphocholine; 1,2-dimyristelaidoyl-sn-glycero-3-phosphocholine; 1,2-dipalmitoleoyl-sn- glycero-3-phosphocholine; 1,2-dipalmitelaidoyl-sn-glycero-3-phosphocholine; 1,2- dipetroselenoyl-sn-glycero-3-phosphocholine; 1,2-dioleoyl-sn-glycero-3-phosphocholine; 1,2- dielaidoyl-sn-glycero-3-phosphocholine; 1,2-dieicosenoyl-sn-glycero-3-phosphocholine; 1,2- dinervonoyl-sn-glycero-3-phosphocholine; 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine; 1,2-dipentadecanoyl-sn-glycero-3- phosphoethanolamine; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine; 1,2-distearoyl-sn- glycero-3-phosphoethanolamine; 1,2-dipalmitoleoyl-sn-glycero-3-phosphoethanolamine; 1,2- dielaidoyl-sn-glycero-3-phosphoethanolamine; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; dioleoyl-sn-glycero-3-phosphoethanolamine-N-[3-(2-pyridyldithio) propionate]; 1,2- dipalmitoyl-sn-glycero-3-phosphothioethanol; 1,2-di-(9Z-octadecenoyl)-sn-glycero-3- phosphoethanolamine-N-[4-(p-maleimidophenyl)butyramide]; 1,2-dihexadecanoyl-sn-glycero- 3-phosphoethanolamine-N-[4-(p-maleimidophenyl)butyramide]; 1,2-dihexadecanoyl-sn- glycero-3-phosphoethanolamine-N-[4-(p-maleimidomethyl)cyclohexane-carboxamide]; 1,2-di- (9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidomethyl)cyclohexane- carboxamide]; N-[(3-Maleimide-1-oxopropyl)aminopropyl polyethyleneglycol-carbamyl] distearoylphosphatidyl-ethanolamine; N-[(3-Maleimide-1-oxopropyl)aminopropyl polyethyleneglycol-carbamyl] distearoylphosphatidyl-ethanolamine; N-(3-Maleimide-1- oxopropyl)-L-α-phosphatidylethanolamine, Distearoyl; N-[(3-Maleimide-1- oxopropyl)aminopropyl polyethyleneglycol-carbamyl] distearoylphosphatidyl-ethanolamine; N- (3-Maleimide-1-oxopropyl)-L-α-phosphatidylethanolamine, Dimyristoy; N-(3-Maleimide-1- oxopropyl)-L-α-phosphatidylethanolamine, Dioleoyl; N-(3-Maleimide-1-oxopropyl)-L-α- phosphatidylethanolamine, Dipalmitoyl; N-(3-Maleimide-1-oxopropyl)-L-α- phosphatidylethanolamine, 1-Palmitoyl-2-oleoyl; phosphatidylcholine; phosphatidylinositol; phosphatidylserine; phosphatidylethanolamine; N-(Succinimidyloxy-glutaryl)-L-α- phosphatidylethanolamine, Distearoyl; N-(Succinimidyloxy-glutaryl)-L-α- phosphatidylethanolamine, Dioleoyl; N-(Succinimidyloxy-glutaryl)-L-α- phosphatidylethanolamine, 1-Palmitoyl-2-oleoyl; N-(Succinimidyloxy-glutaryl)-L-α- phosphatidylethanolamine, Dipalmitoyl; N-(Succinimidyloxy-glutaryl)-L-α- phosphatidylethanolamine, Dimyristoyl; 3-(N-succinimidyloxyglutaryl)aminopropyl, and polyethyleneglycol-carbamyl distearoylphosphatidyl-ethanolamine; N-(3-oxopropoxy polyethyleneglycol)carbamyl-distearoyl-ethanolamine. In some embodiments, the sHDL nanoparticles have a molar ratio of phospholipid / HDL apolipoprotein from 2 to 250 (e.g., 10 to 200, 20 to 100, 20 to 50, 30 to 40). UM-41715.601 Generally, the sHDL nanoparticles so formed are spherical or discoidal and have a diameter of from about 5 nm to about 20 nm (e.g., 4-75 nm, 4-60 nm, 4-50 nm, 4-22 nm, 6-18 nm, 8-15 nm, 8-10 nm, etc.). In some embodiments, the sHDL nanoparticles are subjected to size exclusion chromatography to yield a more homogeneous preparation. Such compositions are not limited to specific types or kinds of peptides. In some embodiments, the peptide comprises a linker moiety connected with a payload moiety, wherein the linker comprises cysteine (C) and one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S), the payload comprises a polypeptide that is 5 to 35 amino acids in length and has a net positive charge at a pH of 7 to 12, and the peptide comprises a net negative charge at a pH of 7 and an isoelectric point of 0.4 to 12; and wherein the peptide is covalently attached to the thiol-reactive lipid by way of the cysteine (C). In some embodiments, the peptide is covalently attached to the thiol-reactive lipid by way of the Cys. In some embodiments, the peptide is covalently attached to the thiol-reactive lipid by way of the carboxy terminus of the Cys. In some embodiments, the peptide is covalently attached to the thiol-reactive lipid by way of the amino terminus of the Cys. In some embodiments, the peptide is covalently attached to the thiol-reactive lipid by way of a non- terminal position terminus of the Cys. In some embodiments, the peptide comprises the formula: [linker]-[payload] or [payload]-[linker]. In some embodiments, the linker sequence is DDCDD. In some embodiments, the one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S) comprises a peptide dimer. In some embodiments, the peptide dimer is selected from DD, SE, SD, and EE. In some embodiments, the one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S) comprises a peptide trimer. In some embodiments, the peptide trimer is selected from DDD, EEE, and KEE.

[0002] UM-41715.601 In some embodiments, the one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S) comprises a peptide 4-mer. In some embodiments, the peptide 4-mer is selected from DDDD (SEQ ID NO:762) and EEEE (SEQ ID NO:763). In some embodiments, the payload has a charge of greater than 0.1 at pH 7. In some embodiments, the payload has a charge ranging from 0.1 to 5.0. In some embodiments, the payload is a polypeptide that is 12 to 35 amino acids in length. In some embodiments, the payload is selected from GWYRSPFSRVVHL (SEQ ID NO:764), NTWTTSQSIAFPSK (SEQ ID NO:765), KVAPVWVRMME (SEQ ID NO:766), KYNKANAFL (SEQ ID NO:767), and ASFEAQGALANIAVDKA (SEQ ID NO:768). In some embodiments, the peptide is an antigen and / or tolerogenic antigen. In some embodiments, the antigen associated with the nanoparticle includes a gliadin polypeptide, such as the full-length gliadin polypeptide or any epitopes of the gliadin polypeptide. In some embodiments, the antigen associated with the nanoparticle includes a 33- mer polypeptide from α2-gliadin. In some embodiments, the 33-mer gliadin polypeptide has at least 90% (at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to the polypeptide sequence of LQLQPFPQPELPYPQPELPYPQPELPYPQPQPF (SEQ ID NO: 374). In some embodiments, the antigen associated with the nanoparticles includes an epitope of the 33-mer gliadin polypeptide. The epitope of the 33-mer gliadin polypeptide may be a polypeptide of any length shorter than the 33-mer polypeptide, for example the epitope may include between 25 and 3 (e.g., 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4 or 3) amino acid residues, between 20 and 5 (e.g., 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, or 5) amino acids residues, between 12 and 6 (e.g., 12, 11, 10, 9, 8, 7 or 6) amino acid residues, or 9 amino acids in length. Further examples of epitopes of the 33-gliadin that may be associated with the nanoparticles include any one of the epitopes described in Table 3, including SEQ ID Nos: 375- 405. In some embodiments, the tolerogenic antigen associated with the nanoparticle may include any one of the antigens described in Table 4, including SEQ ID Nos: 406-580. In some embodiments, the antigen associated with the nanoparticles includes a polypeptide sequence having at least 85% (e.g., at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 95%, or 100%) sequence identity to any one of SEQ ID Nos: 375-580. In some embodiments, the tolerogenic antigen associated with the nanoparticle may include an antigen including two or more (e.g., 2, 3, 4, 5, or 6) polypeptides having the polypeptide sequences of any two of SEQ ID Nos: 375-580. In some embodiments, the plurality of tolerogenic antigens (e.g., between 1 – 30 (e.g., 6 – 30, or 8 – 30 (e.g., 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, UM-41715.601 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30)) tolerogenic antigens per nanoparticle) associated with the nanoparticles have the same identity as every other tolerogenic antigen associated with the nanoparticle. In some embodiments, the plurality of tolerogenic antigens associated with the nanoparticles includes a population of between 2-10 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10) different antigen sequences implicated in the same disease; for example, the nanoparticles may be associated with between 3-8 (e.g., 3, 4, 5, 6, 7, or 8), 4-6 (e.g., 4, 5, or 6), or 3-4 different polypeptide antigen sequences. In some embodiments, the nanoparticles may be associated with (i) a first polypeptide population comprising the amino acid sequence of any one of SEQ ID Nos: 406-580, or a biologically active fragment or variant thereof, (ii) a second polypeptide population comprising the amino acid sequence of any one of SEQ ID Nos: 406-580, or biologically active fragment or variant thereof, and (iii) a third polypeptide population comprising the amino acid sequence of any one of SEQ ID Nos: 406-580, or a biologically active fragment or variant thereof. In some instances, the first, second, and third polypeptide populations have different amino acid sequences. In some embodiments, the nanoparticles may be associated with (i) a first polypeptide comprising the amino acid sequence LQPFPQPELPYPQPQ (SEQ ID NO: 474), or a biologically active fragment or variant thereof, (ii) a second polypeptide comprising the amino acid sequence QPFPQPEQPFPWQP (SEQ ID NO: 475), or a biologically active fragment or variant thereof, and (iii) a third polypeptide comprising the amino acid sequence PEQPIPEQPQPYPQQ (SEQ ID NO: 476), or a biologically active fragment or variant thereof. In some embodiments, the nanoparticles may be associated with (i) a first polypeptide comprising the amino acid sequence LQPFPQPELPYPQPQ (SEQ ID NO: 474), or a biologically active fragment or variant thereof, (ii) a second polypeptide comprising the amino acid sequence PQQPFPQPEQPFPWQP (SEQ ID NO: 477), or a biologically active fragment or variant thereof, and (iii) a third polypeptide comprising the amino acid sequence FPEQPIPEQPQPYPQQ (SEQ ID NO: 478), or a biologically active fragment or variant thereof. In some embodiments, the nanoparticles may be associated with (i) a first polypeptide comprising the amino acid sequence ELQPFPQPELPYPQPQ (SEQ ID NO: 506), or a biologically active fragment or variant thereof, (ii) a second polypeptide comprising the amino acid sequence EQPFPQPEQPFPWQP (SEQ ID NO: 507), or a biologically active fragment or variant thereof, and (iii) a third polypeptide comprising the amino acid sequence EPEQPIPEQPQPYPQQ (SEQ ID NO: 508), or a biologically active fragment or variant thereof. In some embodiments, the tolerogenic antigens having polypeptide sequences of SEQ ID Nos: 506, 507, and 508 include an N-terminus pyroglutamic acid (pyroE). In some embodiments described herein, the tolerogenic antigens UM-41715.601 having polypeptide sequences of SEQ ID Nos: 506, 507, and 508 include a C-terminus amide group. In some embodiments described herein, the tolerogenic antigens having polypeptide sequences of SEQ ID Nos: 506, 507, and 508 include a N-terminus pyroE residue and a C- terminus amide group. In some embodiments, the nanoparticles may be associated with (i) a first polypeptide comprising the amino acid sequence QLQPFPQPELPYPQPQ (SEQ ID NO: 509), or a biologically active fragment or variant thereof, (ii) a second polypeptide comprising the amino acid sequence QQPFPQPEQPFPWQP (SEQ ID NO: 510), or a biologically active fragment or variant thereof, and (iii) a third polypeptide comprising the amino acid sequence FPEQPIPEQPQPYPQQ (SEQ ID NO: 511), or a biologically active fragment or variant thereof. In some embodiments, the tolerogenic antigens having polypeptide sequences of SEQ ID Nos: 509, 510, and 511 include an N-terminus acetyl group. In some embodiments described herein, the tolerogenic antigens having polypeptide sequences of SEQ ID Nos: 509, 510, and 511 include a C-terminus amide group. In some embodiments described herein, the tolerogenic antigens having polypeptide sequences of SEQ ID Nos: 509, 510, and 511 include a N-terminus acetyl group and a C-terminus amide group. In any of the embodiments described herein, the population of antigens associated with the nanoparticle may be fully or partially deamidated. In some embodiments described herein, the tolerogenic antigens associated with the nanoparticle may include an N-terminus pyroglutamic acid (pyroE). In some embodiments described herein, the tolerogenic antigens associated with the nanoparticle may include an N-terminus acetyl group. In some embodiments described herein, the tolerogenic antigens associated with the nanoparticle may include an N-terminus amide group. In some embodiments described herein, the tolerogenic antigens associated with the nanoparticle may include a C-terminus amide group. Table 3: Celiac Disease Relevant T-cell epitopes recognized by CD4+T cells SEQ ID NO: Sequence UM-41715.601 SEQ ID NO: Sequence 384 QQPEQPFPQ Table 4: Tolerogenic Antigens SEQ ID Sequence SEQ ID NO: Sequence P UM-41715.601 SEQ ID Sequence SEQ ID NO: Sequence NO: Q P Q Q P Q UM-41715.601 SEQ ID Sequence SEQ ID NO: Sequence NO: UM-41715.601 SEQ ID Sequence SEQ ID NO: Sequence NO: In some embodiments, the tolerogenic antigen is a biologically active fragment of SEQ ID NO: 474. In some instances, the biologically active fragment of SEQ ID NO: 474 includes a polypeptide comprising the sequence of SEQ ID NO: 512. In some instances, the biologically active fragment of SEQ ID NO: 474 includes a polypeptide comprising the sequence of SEQ ID NO: 580. UM-41715.601 In some instances, the tolerogenic antigen is a biologically active fragment of SEQ ID NO: 475. In some instances, the biologically active fragment of SEQ ID NO: 475 includes a polypeptide comprising the sequence of SEQ ID NO: 542. In some embodiments, the tolerogenic antigen is a biologically active fragment of SEQ ID NO: 476. In some instances, the biologically active fragment of SEQ ID NO: 476 includes a polypeptide comprising the sequence of SEQ ID NO: 563. In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQPELPY (SEQ ID NO: 375). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PYPQPELPY (SEQ ID NO: 376). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPELPYPQ (SEQ ID NO: 377). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FRPEQPYPQ (SEQ ID NO: 378). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQSFPEQQ (SEQ ID NO: 379). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence IQPEQPAQL (SEQ ID NO: 380). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQPEQPYPQ (SEQ ID NO: 381). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence SQPEQEFPQ (SEQ ID NO: 382). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPEQEFPQ (SEQ ID NO: 383). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQPEQPFPQ (SEQ ID NO: 384). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPEQPFCQ (SEQ ID NO: 385). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQPFPEQPQ (SEQ ID NO: 386). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQPEQPF (SEQ ID NO: 387). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPEQPFPW (SEQ ID NO: 388). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFSEQEQPV (SEQ ID NO: 389). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FSQQQESPF (SEQ ID NO: 390). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQPIPEQPQ (SEQ ID NO: 391). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPEQPFPQ (SEQ ID NO: 392). In some embodiments, the tolerogenic antigen UM-41715.601 comprises a polypeptide comprising the amino acid sequence PIPEQPQPY (SEQ ID NO: 393). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence EQPIPEQPQ (SEQ ID NO: 394). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPEQPFPQ (SEQ ID NO: 395). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PYPEQEEPF (SEQ ID NO: 396). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PYPEQEQPF (SEQ ID NO: 397). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFSEQEQPV (SEQ ID NO: 398). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence EGSFQPSQE (SEQ ID NO: 399). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence EQPQQPFPQ (SEQ ID NO: 400). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence EQPQQPYPE (SEQ ID NO: 401). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QGYYPTSPQ (SEQ ID NO: 402). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence EGSFQPSQE (SEQ ID NO: 403). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQSFPEQE (SEQ ID NO: 404). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QGYYPTSPQ (SEQ ID NO: 405). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQQPFPW (SEQ ID NO: 406). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQQPIPV (SEQ ID NO: 407). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQPFPW (SEQ ID NO: 408). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQPEQPIPV (SEQ ID NO: 409). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPELPFPQ (SEQ ID NO: 410). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LPYPQPQLPYPQ (SEQ ID NO: 411). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LPYPQPELPYPQ (SEQ ID NO: 412). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQLPYPQ (SEQ ID NO: 413). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPELPYPQ (SEQ ID NO: 414). In some embodiments, the UM-41715.601 tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQQPFSQ (SEQ ID NO: 415). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQPFSQ (SEQ ID NO: 416). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQQPFCQ (SEQ ID NO: 417). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQPFCQ (SEQ ID NO: 418). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQLPYSQ (SEQ ID NO: 419). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPELPYSQ (SEQ ID NO: 420). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LQQQCSPVAMPQRLAR (SEQ ID NO: 421). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQLPYLQ (SEQ ID NO: 422). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPELPYLQ (SEQ ID NO: 423). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQFIQPQQPFPQ (SEQ ID NO: 424). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQFIQPEQPFPQ (SEQ ID NO: 425). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LERPWQQQPLPP (SEQ ID NO: 426). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LERPWQEQPLPP (SEQ ID NO: 427). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PIPQQPEQPFPL (SEQ ID NO: 428). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QGQQGYYPISPQQSGQ (SEQ ID NO: 429). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QGQPGYYPTSPQQIGQ (SEQ ID NO: 430). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PGQGQSGYYPTSPQQS (SEQ ID NO: 431). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQTFPQQPQLP (SEQ ID NO: 432). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQTFPEQPQLP (SEQ ID NO: 433). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence GQGQSGYYPTSPQQSG (SEQ ID NO: 434). In some embodiments, the tolerogenic antigen comprises a polypeptide UM-41715.601 comprising the amino acid sequence QYEVIRSLVLRTLPNM (SEQ ID NO: 435). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QVDPSGQVQWPQ (SEQ ID NO: 436). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QVDPSGEVQWPQ (SEQ ID NO: 437). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQQPFPL (SEQ ID NO: 438). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQPFPL (SEQ ID NO: 439). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQQPIPY (SEQ ID NO: 440). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQPIPY (SEQ ID NO: 441). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQPVPQQPQPY (SEQ ID NO: 442). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQPVPEQPQPY (SEQ ID NO: 443). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPFPQQPIPQQPQPY (SEQ ID NO: 444). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQPIPQQPQPY (SEQ ID NO: 445). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQPIPEQPQPY (SEQ ID NO: 446). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQFPQPQQPFPQ (SEQ ID NO: 447). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQFPQPEQPFPQ (SEQ ID NO: 448). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQPIPQQPQPYPQQP (SEQ ID NO: 449). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQPFPQQPFPQQPQPY (SEQ ID NO: 450). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQQPFSW (SEQ ID NO: 451). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQPFSW (SEQ ID NO: 452). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQPFPQQPQPYPQQP (SEQ ID NO: 453). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQQPIPQ (SEQ ID NO: 454). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQPIPQ (SEQ ID NO: 455). In some embodiments, the UM-41715.601 tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQQPFPQ (SEQ ID NO: 456). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQPFPQ (SEQ ID NO: 457). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQQPTPI (SEQ ID NO: 458). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQPTPI (SEQ ID NO: 459). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PAPIQPQQPFPQ (SEQ ID NO: 460). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PAPIQPEQPFPQ (SEQ ID NO: 461). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQPFPQQPEQI (SEQ ID NO: 462). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQPFPEQPEQI (SEQ ID NO: 463). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQPFPQQPQQI (SEQ ID NO: 464). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQPFPEQPQQI (SEQ ID NO: 465). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQQPEQIISQ (SEQ ID NO: 466). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQQPEQIISQ (SEQ ID NO: 467). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQQPEQIIPQ (SEQ ID NO: 468). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQQPEQIIPQ (SEQ ID NO: 469). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPQQQLPL (SEQ ID NO: 470). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQQLPL (SEQ ID NO: 471). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LFPLPQQPFPQ (SEQ ID NO: 472). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LFPLPEQPFPQ (SEQ ID NO: 473). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LQPFPQPELPYPQPQ (SEQ ID NO: 474). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQPFPWQP (SEQ ID NO: 475). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PEQPIPEQPQPYPQQ (SEQ ID NO: 476). In some UM-41715.601 embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQPFPQPEQPFPWQP (SEQ ID NO: 477). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPEQPIPEQPQPYPQQ (SEQ ID NO: 478). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PEQPIPEQPQPYPQQ (SEQ ID NO: 479). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPFLPQLPYPQ (SEQ ID NO: 480). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QAFPQPQQTFPH (SEQ ID NO: 481). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence TPIQPQQPFPQ (SEQ ID NO: 482). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPLQPQQPFPQ (SEQ ID NO: 483). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFTQPQQPTPI (SEQ ID NO: 484). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQLQQPQQP (SEQ ID NO: 485). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence VAHAIIMHQQQQQQQE (SEQ ID NO: 486). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence SYPVQPQQPFPQ (SEQ ID NO: 487). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQQPQPFPQQPVPQQP (SEQ ID NO: 488). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPWQPQQPFPQ (SEQ ID NO: 489). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPLQPQQPFPQ (SEQ ID NO: 490). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQPFQPQQPFPQ (SEQ ID NO: 491). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence NPLQPQQPFPLQPQPP (SEQ ID NO: 492). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PLQPQQPFPLQPQPPQ (SEQ ID NO: 493). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PNPLQPQQPFPLQ (SEQ ID NO: 494). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence TIPQQPQQPFPL (SEQ ID NO: 495). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence SFSQQPQQPFPL (SEQ ID NO: 496). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence UM-41715.601 SFSEQPQQPFPL (SEQ ID NO: 497). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence YSPYQPQQPFPQ (SEQ ID NO: 498). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QLPLQPQQPFPQ (SEQ ID NO: 499). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQPQQPFPLQPQQPVP (SEQ ID NO: 500). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence IIPQQPQQPFPL (SEQ ID NO: 501). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PEQIIPQQPQQP (SEQ ID NO: 502). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FLLQPQQPFSQ (SEQ ID NO: 503). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence IISQQPQQPFPL (SEQ ID NO: 504). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQRPQQPFPQ (SEQ ID NO: 505). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence ELQPFPQPELPYPQPQ (SEQ ID NO: 506). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence EQPFPQPEQPFPWQP (SEQ ID NO: 507). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence EPEQPIPEQPQPYPQQ (SEQ ID NO: 508). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QLQPFPQPELPYPQPQ (SEQ ID NO: 509). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QQPFPQPEQPFPWQP (SEQ ID NO: 510). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPEQPIPEQPQPYPQQ (SEQ ID NO: 511). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PELP (SEQ ID NO: 512). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPELPYP (SEQ ID NO: 513). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPELPY (SEQ ID NO: 514). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPQPELP (SEQ ID NO: 515). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PELPYPQP (SEQ ID NO: 516). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPELPYPQ (SEQ ID NO: 517). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPELPYP (SEQ ID NO: 518). UM-41715.601 In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPQPELPY (SEQ ID NO: 519). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQPELP (SEQ ID NO: 520). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PELPYPQPQ (SEQ ID NO: 521). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPELPYPQP (SEQ ID NO: 522). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPQPELPYP (SEQ ID NO: 523). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQPELPY (SEQ ID NO: 524). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPELP (SEQ ID NO: 525). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPELPYPQPQ (SEQ ID NO: 526). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPELPYPQP (SEQ ID NO: 527). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPQPELPYPQ (SEQ ID NO: 528). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQPELPYP (SEQ ID NO: 529). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPELPY (SEQ ID NO: 530). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LQPFPQPELP (SEQ ID NO: 531). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPELPYPQPQ (SEQ ID NO: 532). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPQPELPYPQP (SEQ ID NO: 533). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQPELPYPQ (SEQ ID NO: 534). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPELPYP (SEQ ID NO: 535). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LQPFPQPELPY (SEQ ID NO: 536). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPQPELPYPQPQ (SEQ ID NO: 537). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQPELPYPQP (SEQ ID NO: 538). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LQPFPQPELPYP (SEQ ID NO: 539). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence UM-41715.601 PFPQPELPYPQPQ (SEQ ID NO: 540). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LQPFPQPELPYPQ (SEQ ID NO: 541). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPEQPF (SEQ ID NO: 542). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPEQPFP (SEQ ID NO: 543). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPEQPF (SEQ ID NO: 544). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPEQPFPW (SEQ ID NO: 545). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPEQPFP (SEQ ID NO: 546). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPQPEQPF (SEQ ID NO: 547). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPEQPFPWQ (SEQ ID NO: 548). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPQPEQPFP (SEQ ID NO: 549). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPEQPFPWQP (SEQ ID NO: 550). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPEQPFPWQ (SEQ ID NO: 551). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPQPEQPFPW (SEQ ID NO: 552). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQPEQPFP (SEQ ID NO: 553). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQPF (SEQ ID NO: 554). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PQPEQPFPWQP (SEQ ID NO: 555). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPQPEQPFPWQ (SEQ ID NO: 556). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQPEQPFPW (SEQ ID NO: 557). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPEQPFP (SEQ ID NO: 558). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence FPQPEQPFPWQP (SEQ ID NO: 559). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQPEQPFPWQ (SEQ ID NO: 560). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PFPQPEQPFPWQP (SEQ ID NO: 561). In some embodiments, the tolerogenic antigen UM-41715.601 comprises a polypeptide comprising the amino acid sequence QPFPQPEQPFPWQ (SEQ ID NO: 562). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PIPEQPQ (SEQ ID NO: 563). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PIPEQPQP (SEQ ID NO: 564). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPIPEQPQ (SEQ ID NO: 565). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPIPEQPQP (SEQ ID NO: 566). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PIPEQPQPYP (SEQ ID NO: 567). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPIPEQPQPY (SEQ ID NO: 568). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence EQPIPEQPQP (SEQ ID NO: 569). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PEQPIPEQPQ (SEQ ID NO: 570). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PIPEQPQPYPQQ (SEQ ID NO: 571). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPIPEQPQPYPQ (SEQ ID NO: 572). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence EQPIPEQPQPYP (SEQ ID NO: 573). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PEQPIPEQPQPY (SEQ ID NO: 574). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPIPEQPQPYPQQ (SEQ ID NO: 575). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence EQPIPEQPQPYPQ (SEQ ID NO: 576). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PEQPIPEQPQPYP (SEQ ID NO: 577). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence EQPIPEQPQPYPQQ (SEQ ID NO: 578). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PEQPIPEQPQPYPQ (SEQ ID NO: 579). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PDLP (SEQ ID NO: 580). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PELPYPQ (SEQ ID NO: 581). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPFPQPELPYPQP (SEQ ID NO: 582). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence UM-41715.601 QPFPQPELPYPQPQ (SEQ ID NO: 583). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence LQPFPQPELPYPQP (SEQ ID NO: 584). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PIPEQPQPYPQ (SEQ ID NO: 585). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence QPIPEQPQPYP (SEQ ID NO: 586). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence EQPIPEQPQPY (SEQ ID NO: 587). In some embodiments, the tolerogenic antigen comprises a polypeptide comprising the amino acid sequence PEQPIPEQPQP (SEQ ID NO: 588). In some embodiments, such tolerogenic antigens include human allograft transplantation antigens. Examples of such human allograft transplantation antigens include, but are not limited to, the subunits of the various MHC class I and MHC class II haplotype proteins, and single- amino-acid polymorphisms on minor blood group antigens including RhCE, Kell, Kidd, Duffy and Ss. In some embodiments, the tolerogenic antigen is a self antigen against which a subject (e.g., a human patient) has developed an autoimmune response or may develop an autoimmune response. Examples include proinsulin (e.g., for subjects suffering from or at risk of suffering from diabetes), collagens (e.g., for subjects suffering from or at risk of suffering from rheumatoid arthritis), and myelin basic protein (e.g., for subjects suffering from or at risk of suffering from multiple sclerosis). There are many proteins that are human autoimmune proteins, a term referring to various autoimmune diseases wherein the protein or proteins causing the disease are known or can be established by routine testing. Embodiments include testing a patient to identify an autoimmune protein and creating an antigen for use in a molecular fusion and creating immunotolerance to the protein. Embodiments include an antigen, or choosing an antigen from, one or more of the following proteins. In type 1 diabetes mellitus, several main antigens have been identified: insulin, proinsulin, preproinsulin, glutamic acid decarboxylase-65 (GAD-65), GAD-67, insulinoma-associated protein 2 (IA-2), and insulinoma- associated protein 2β (IA-2β); other antigens include ICA69, ICA12 (SOX-13), carboxypeptidase H, Imogen 38, GLIMA 38, chromogranin-A, HSP-60, carboxypeptidase E, peripherin, glucose transporter 2, hepatocarcinoma-intestine-pancreas / pancreatic associated protein, S100β, glial fibrillary acidic protein, regenerating gene II, pancreatic duodenal homeobox 1, dystrophia myotonica kinase, islet-specific glucose-6-phosphatase catalytic subunit-related protein, and SST G-protein coupled receptors 1-5. In autoimmune diseases of the thyroid, including Hashimoto’s thyroiditis and Graves’ disease, main antigens include UM-41715.601 thyroglobulin (TG), thyroid peroxidase (TPO) and thyrotropin receptor (TSHR); other antigens include sodium iodine symporter (NIS) and megalin. In thyroid-associated ophthalmopathy and dermopathy, in addition to thyroid autoantigens including TSHR, an antigen is insulin-like growth factor 1 receptor. In hypoparathyroidism, a main antigen is calcium sensitive receptor. In Addison’s disease, main antigens include 21-hydroxylase, 17α-hydroxylase, and P450 side chain cleavage enzyme (P450scc); other antigens include ACTH receptor, P450c21 and P450c17. In premature ovarian failure, main antigens include FSH receptor and α-enolase. In autoimmune hypophysitis, or pituitary autoimmune disease, main antigens include pituitary gland-specific protein factor (PGSF) 1a and 2; another antigen is type 2 iodothyronine deiodinase. In multiple sclerosis, main antigens include myelin basic protein, myelin oligodendrocyte glycoprotein and proteolipid protein. In rheumatoid arthritis, a main antigen is collagen II. In immunogastritis, a main antigen is H+, K+-ATPase. In pernicious angemis, a main antigen is intrinsic factor. In celiac disease, main antigens are tissue transglutaminase and gliadin. In vitiligo, a main antigen is tyrosinase, and tyrosinase related protein 1 and 2. In myasthenia gravis, a main antigen is acetylcholine receptor. In pemphigus vulgaris and variants, main antigens are desmoglein 3, 1 and 4; other antigens include pemphaxin, desmocollins, plakoglobin, perplakin, desmoplakins, and acetylcholine receptor. In bullous pemphigoid, main antigens include BP180 and BP230; other antigens include plectin and laminin 5. In dermatitis herpetiformis Duhring, main antigens include endomysium and tissue transglutaminase. In epidermolysis bullosa acquisita, a main antigen is collagen VII. In systemic sclerosis, main antigens include matrix metalloproteinase 1 and 3, the collagen-specific molecular chaperone heat-shock protein 47, fibrillin-1, and PDGF receptor; other antigens include Scl-70, U1 RNP, Th / To, Ku, Jo1, NAG-2, centromere proteins, topoisomerase I, nucleolar proteins, RNA polymerase I, II and III, PM-Slc, fibrillarin, and B23. In mixed connective tissue disease, a main antigen is U1snRNP. In Sjogren’s syndrome, the main antigens are nuclear antigens SS-A and SS-B; other antigens include fodrin, poly(ADP-ribose) polymerase and topoisomerase. In systemic lupus erythematosus, main antigens include nuclear proteins including SS-A, high mobility group box 1 (HMGB1), nucleosomes, histone proteins and double-stranded DNA. In Goodpasture’s syndrome, main antigens include glomerular basement membrane proteins including collagen IV. In rheumatic heart disease, a main antigen is cardiac myosin. Other autoantigens revealed in autoimmune polyglandular syndrome type 1 include aromatic L-amino acid decarboxylase, histidine decarboxylase, cysteine sulfinic acid decarboxylase, tryptophan hydroxylase, tyrosine hydroxylase, phenylalanine hydroxylase, hepatic P450 cytochromes UM-41715.601 P4501A2 and 2A6, SOX-9, SOX-10, calcium-sensing receptor protein, and the type 1 interferons interferon alpha, beta and omega. In some cases, the tolerogenic antigen is a foreign antigen against which a patient has developed an unwanted immune response. Examples are food antigens. Embodiments include testing a patient to identify foreign antigen and creating a molecular fusion that comprises the antigen and treating the patient to develop immunotolerance to the antigen or food. Examples of such foods and / or antigens are provided. Examples are from peanut: conarachin (Ara h 1), allergen II (Ara h 2), arachis agglutinin, conglutin (Ara h 6); from apple: 31 kDa major allergen / disease resistance protein homolog (Mal d 2), lipid transfer protein precursor (Mal d 3), major allergen Mal d 1.03D (Mal d 1): from milk: α-lactalbumin (ALA), lactotransferrin; from kiwi: actinidin (Act c 1, Act d 1), phytocystatin, thaumatin-like protein (Act d 2), kiwellin (Act d 5); from mustard: 2S albumin (Sin a 1), 11S globulin (Sin a 2), lipid transfer protein (Sin a 3), profilin (Sin a 4); from celery: profilin (Api g 4), high molecular weight glycoprotein (Api g 5); from shrimp: Pen a 1 allergen (Pen a 1), allergen Pen m 2 (Pen m 2), tropomyosin fast isoform; from wheat and / or other cereals: high molecular weight glutenin, low molecular weight glutenin, alpha- and gamma-gliadin, hordein, secalin, avenin; from strawberry: major strawberry allergy Fra a 1-E (Fra a 1), from banana: profilin (Mus xp 1). In some embodiments, the tolerogenic antigens are antigenic peptides of any one of SEQ ID Nos: 589-742 (Table 5). Table 5. Tolerogenic Antigens SEQ ID Sequence Origin g UM-41715.601 SEQ ID Sequence Origin NO: UM-41715.601 SEQ ID Sequence Origin NO: UM-41715.601 SEQ ID Sequence Origin NO: al UM-41715.601 SEQ ID Sequence Origin NO: UM-41715.601 SEQ ID Sequence Origin NO: UM-41715.601 SEQ ID Sequence Origin NO: UM-41715.601 SEQ ID Sequence Origin NO: l UM-41715.601 SEQ ID Sequence Origin NO: UM-41715.601 SEQ ID Sequence Origin NO: UM-41715.601 SEQ ID Sequence Origin NO: n certa n em o ments, am no ac sequence var ants o t e to erogen c ant gens o the invention are contemplated. For example, it may be desirable to improve the tolerogenic antigenicity and / or other biological properties of the tolerogenic antigens. Amino acid sequence variants of a tolerogenic antigen may be prepared by introducing appropriate modifications into the nucleotide sequence encoding the tolerogenic antigen, or by peptide synthesis. Such modifications include, for example, deletions from, and / or insertions into and / or substitutions of residues within the amino acid sequences of the tolerogenic antigens. Any combination of deletion, insertion, and substitution can be made to arrive at the final construct, provided that the final construct possesses the desired characteristics, for example, inducing antigen tolerance. In certain embodiments, tolerogenic antigen variants having one or more amino acid substitutions are provided. Conservative substitutions are shown in Table 6 under the heading of “preferred substitutions.” More substantial changes are provided in Table 6 under the heading of “exemplary substitutions,” and as further described below in reference to amino acid side chain classes. Amino acid substitutions may be introduced into a tolerogenic antigen of interest and the products screened for a desired activity, for example, retained / improved tolerogenic antigenicity. UM-41715.601 Table 6. Exemplary and Preferred Amino Acid Substitutions Original Exemplary Preferred Residue Substitutions Substitutions Amino acids may be grouped according to common side-chain properties: (1) hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile; (2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues that influence chain orientation: Gly, Pro; (6) aromatic: Trp, Tyr, Phe. UM-41715.601 Non-conservative substitutions will entail exchanging a member of one of these classes for another class. A useful method for identification of residues or regions of a tolerogenic antigen that may be targeted for mutagenesis is called “alanine scanning mutagenesis” as described by Cunningham and Wells (1989) Science, 244:1081-1085. In this method, a residue or group of target residues (e.g., charged residues such as Arg, Asp, His, Lys, And Glu) are identified and replaced by a neutral or negatively charged amino acid (e.g., alanine or polyalanine) to determine whether the interaction of the antibody with antigen is affected. Further substitutions may be introduced at the amino acid locations demonstrating functional sensitivity to the initial substitutions. Alternatively, or additionally, a crystal structure of an antigen-antibody complex to identify contact points between the antibody and antigen. Such contact residues and neighboring residues may be targeted or eliminated as candidates for substitution. Tolerogenic antigen variants may be screened to determine whether they contain the desired properties. Amino acid sequence insertions include amino- and / or carboxyl-terminal fusions ranging in length from one residue to polypeptides containing a hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. In some embodiments, the tolerogenic antigen includes an amide group at the C- terminus. In certain embodiments, the tolerogenic antigen includes a pyroglutamic acid residue at the N-terminus. In another embodiment, the tolerogenic antigen includes an acetyl group at the N-terminus. In some embodiments, the tolerogenic antigen includes a pyroglutamic acid residue at the N-terminus and an amide group at the C-terminus. In some embodiments, the tolerogenic antigen includes an acetyl group at the N-terminus and an amide group at the C- terminus. In certain embodiments, the tolerogenic antigen includes an N-terminus or a C- terminus modified with a cysteine residue bound to a linker. In some embodiments, the tolerogenic antigen includes an N-terminus and a C-terminus modified with cysteine residues bound to a linker. In some embodiments of any one of the compositions described herein, the population of tolerogenic antigens are conjugated with the nanoparticle phospholipid in such a manner that facilitates strong immune tolerance upon administration to a subject (e.g., a human subject suffering from or at risk of suffering from an autoimmune disorder e.g., MS, celiac disease, rheumatoid arthritis, primary biliary cholangitis, primary sclerosing cholangitis, MOG antibody disease, diabetes (e.g., type 1 diabetes mellitus), autoimmune diseases of the thyroid (e.g., Hashimoto’s thyroiditis, Graves’ disease), thyroid-associated ophthalmopathy and dermopathy, hypoparathyroidism, Addison’s disease, premature ovarian failure, autoimmune hypophysitis, UM-41715.601 pituitary autoimmune disease, immunogastritis, pernicious angemis, celiac disease, vitiligo, myasthenia gravis, pemphigus vulgaris and variants, bullous pemphigoid, dermatitis herpetiformis Duhring, epidermolysis bullosa acquisita, systemic sclerosis, mixed connective tissue disease, Sjogren’s syndrome, systemic lupus erythematosus, Goodpasture’s syndrome, rheumatic heart disease, autoimmune polyglandular syndrome type 1, Aicardi–Goutières syndrome, Acute pancreatitis Age-dependent macular degeneration, Alcoholic liver disease, Liver fibrosis, Metastasis, Myocardial infarction, Nonalcoholic steatohepatitis (NASH), Parkinson’s disease, Polyarthritis / fetal and neonatal anemia, Sepsis, or inflammatory bowel disease). Such peptides can be prepared by a number of techniques known in the art, depending on that nature of the molecule. Short peptides are conveniently prepared by amino acid synthesis. Longer proteins of known sequence can be prepared by synthesizing an encoding sequence or PCR-amplifying an encoding sequence from a natural source or vector, and then expressing the encoding sequence in a suitable bacterial or eukaryotic host cell. The nanoparticles of the present invention may be characterized for size and uniformity by any suitable analytical techniques. These include, but are not limited to, atomic force microscopy (AFM), electrospray-ionization mass spectroscopy, MALDI-TOF mass spectroscopy, LC-MS / MS,13C nuclear magnetic resonance spectroscopy, high performance liquid chromatography (HPLC), size exclusion chromatography (SEC) (equipped with multi- angle laser light scattering, dual UV and refractive index detectors), capillary electrophoresis, and get electrophoresis. These analytical methods assure the uniformity of the sHDL nanoparticle population and are important in the production quality control for eventual use in in vivo applications. In some embodiments, gel permeation chromatography (GPC), which can separate sHDL nanoparticles from liposomes and free ApoA-I mimetic peptide, is used to analyze the sHDL nanoparticles. In some embodiments, the size distribution and zeta-potential are determined by dynamic light scattering (DLS) using, for example, a Malven Nanosizer instrument. Such compositions comprising nanoparticles associated with peptides as described herein are not limited to a particular manner of administering the composition to a subject. Indeed, any acceptable method known to one of ordinary skill in the art may be used to administer such compositions to the subject. The administration may be localized (i.e., to a particular region, physiological system, tissue, organ, or cell type) or systemic. Such compositions can be administered by a number of routes including, but not limited to oral, inhalation (nasal or pulmonary), intravenous, intraperitoneal, intramuscular, transdermal, subcutaneous, topical, UM-41715.601 subcutaneous, sublingual, or rectal means. Injections can be e.g., intravenous, intradermal, subcutaneous, intramuscular, or intraperitoneal. In some embodiments, the injections can be given at multiple locations. Where clinical applications are contemplated, in some embodiments of the present invention, the compositions comprising nanoparticles associated with peptides as described herein are prepared as part of a pharmaceutical composition in a form appropriate for the intended application. Generally, this entails preparing compositions that are essentially free of pyrogens, as well as other impurities that could be harmful to humans or animals. However, in some embodiments of the present invention, a straight composition comprising nanoparticles associated with peptides as described herein may be administered using one or more of the routes described herein. In preferred embodiments, the compositions are used in conjunction with appropriate salts and buffers to render delivery of the compositions in a stable manner to allow for uptake by target cells. Buffers also are employed when either of the compositions are introduced into a patient. Aqueous compositions comprise an effective amount of the sHDL nanoparticles to cells dispersed in a pharmaceutically acceptable carrier or aqueous medium. Such compositions also are referred to as inocula. The phrase "pharmaceutically or pharmacologically acceptable" refer to molecular entities and compositions that do not produce adverse, allergic, or other untoward reactions when administered to an animal or a human. As used herein, "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like. Except insofar as any conventional media or agent is incompatible with the vectors or cells of the present invention, its use in therapeutic compositions is contemplated. Supplementary active ingredients may also be incorporated into the compositions. The active compositions may also be administered parenterally or intraperitoneally or intratumorally. Solutions of the active compounds as free base or pharmacologically acceptable salts are prepared in water suitably mixed with a surfactant, such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions UM-41715.601 or dispersions. The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity can be maintained, for example, by the use of a coating, such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. The prevention of the action of microorganisms can be brought about by various antibacterial an antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it may be preferable to include isotonic agents, for example, sugars or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin. Sterile injectable solutions are prepared by incorporating either of the compositions in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the various sterilized active ingredients into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum-drying and freeze-drying techniques which yield a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof. Upon formulation, either of the compositions are administered in a manner compatible with the dosage formulation and in such amount as is therapeutically effective. The formulations are easily administered in a variety of dosage forms such as injectable solutions, drug release capsules and the like. For parenteral administration in an aqueous solution, for example, the solution is suitably buffered, if necessary, and the liquid diluent first rendered isotonic with sufficient saline or glucose. These particular aqueous solutions are especially suitable for intravenous, intramuscular, subcutaneous, and intraperitoneal administration. For example, one dosage could be dissolved in 1 ml of isotonic NaCl solution and either added to 1000 ml of hypodermoclysis fluid or injected at the proposed site of infusion, (see for example, "Remington's Pharmaceutical Sciences" 15th Edition, pages 1035-1038 and 1570-1580). In some embodiments of the present invention, the active particles or agents are formulated within a therapeutic mixture to comprise about 0.0001 to 1.0 milligrams, or about 0.001 to 0.1 milligrams, or about 0.1 to 1.0 or even about 10 milligrams per dose or so. Multiple doses may be administered. UM-41715.601 Additional formulations that are suitable for other modes of administration include vaginal suppositories and pessaries. A rectal pessary or suppository may also be used. Suppositories are solid dosage forms of various weights and shapes, usually medicated, for insertion into the rectum, vagina, or the urethra. After insertion, suppositories soften, melt or dissolve in the cavity fluids. In general, for suppositories, traditional binders and carriers may include, for example, polyalkylene glycols or triglycerides; such suppositories may be formed from mixtures containing the active ingredient in the range of 0.5% to 10%, preferably 1%-2%. Vaginal suppositories or pessaries are usually globular or oviform and weighing about 5 g each. Vaginal medications are available in a variety of physical forms, e.g., creams, gels, or liquids, which depart from the classical concept of suppositories. The compositions also may be formulated as inhalants. In some embodiments, the present invention also provides kits comprising a composition comprising one or more nanoparticles associated with a peptide as described herein. In some embodiments, the kits comprise one or more of the reagents and tools necessary to generate either composition, and methods of using either of such compositions. EXAMPLES The following example is provided in order to demonstrate and further illustrate certain preferred embodiments and aspects of the present invention and are not to be construed as limiting the scope thereof. Use of pronouns such as, “we”, “our,” and “I” refer to the inventive entity. Example I. Synthesis of sHDL NDs carrying peptides with pI value < 7 and net charge of < 0 at pH 7. Methods Preparation of antigen-loaded sHDL NDs. DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and DOPE-MAL (N-(3- Maleimide-1-oxopropyl)-L-α-phosphatidylethanolamine) were purchased from NOF AMERICA CORPORATION. ApoA1-mimetic peptide 22A (PVLDLFRELLBELLEALKQKLK) (SEQ ID NO:769) was synthesized by GenScript Biotech. All other peptides used in the study were synthesized by Genemed Synthesis Inc. The list of antigen peptides used in this study is shown in Table 7.106,.y5ti1l7ib14ul-osMrUeta uqdee retib d d d d dsdauloo oo o o o eao o o WosG G G G G dioltpn eeph 7= r weie,grHy teap 1.1 1 1h0. . .1. 17t cn Nhc@ -1-2-1-2- er eiacifI1 2 9 9 7p.6.4. . .nf3 3 3weoghSni3 4 .IdaDI :47 4 5 7 4 6 7 4 7 7 47 eoll Q. pdO nESN ma a,)A A xE 4.K K D ni 7D = V V stAIAIneHp(N N AmirArefeLc LA A ep fne L L LK KGQGQxeubuqK EEFEFA Aeetes FhtaN N NEh eFEFdiIIIIII S Snipst SSSESEASAEdopePSCSCE S SeshC C Cpu seML L Ldim K K K EtFEFEFp01epni eNININIdiISISISaEaEeth ytTilp-eS-E-E-S-EPSCSCECSCSC.i7baetlsb raieThtDI 1 2 3 4 5 UM-41715.601 To produce blank sHDL NDs, DMPC and 22A peptide powder were mixed and hydrated in 10 mM sodium phosphate buffer (DMPC: 22A = 2 : 1, mass ratio) with pH = 7.4, which was then subjected to heating and cooling cycles to obtain blank sHDL NDs, followed by sonication for 1 min at room temperature. To load antigen peptide into blank NDs, cysteine-terminated antigen peptide was first conjugated with DOPE-MAL (antigen peptide: DOPE-MAL = 1.5 : 1, molar ratio). Then DOPE-peptide conjugate was added to blank NDs (22A: antigen peptide = 4 : 1, mass ratio) and incubated at room temperature with gentle shaking on an orbital shaker for 1 h. Unreacted antigen peptides were removed by using Zeba Spin desalting columns (Pierce). Size distribution measurement by dynamic light scattering (DLS). The hydrodynamic sizes of peptide-loaded NDs were measured by dynamic light scattering (DLS, Malvern Zetasizer Nano ZSP) in 10 mM phosphate buffer (pH = 7.4). The parameter settings for refractive index (RI) and absorption were 1.45 and 0.001, respectively. Dispersant: phosphate buffer, temperature / Viscosity = 25°C / 0.89 with RI of 1.333. Method: Mark-Houwink (default setting) for size measurement. Temperature: 25°C. Equilibration time: 120 seconds. Cell Type: Disposable cuvettes ZEN0040. Measurement angle: 173 Backscatter (NIBS default). Measurement duration: automatic with 11 runs of 10 seconds for 3 measurements. Readout: size distribution by volume and intensity. Loading efficiency measurement by Liquid chromatography-mass spectrometry (LC-MS). The chromatogram of DOPE-peptides was characterized by LC-MS (Shimadzu LCMS- 2020 + LC-2040C) with a Biphenyl column (1.7 mm, 50 x 2.1 mm, 100A, Phenomenex). The mobile phase was a mixture of water, acetonitrile, and methanol. Samples were diluted 100-fold in methanol. The loading efficiencies were calculated by comparing the area under the curve (AUC) of DOPE-peptides in LC-MS chromatogram before and after the purification. Results We first studied how to prepare sHDL NDs loaded with peptides with pI value < 7 and net charge of < 0 at pH 7. We chose CSS-SIINFEKL (SEQ ID NO:743) and CSS-Ea (CSS- ASFEAQGALANIAVDKA) (SEQ ID NO:746) for these studies, as they have the pI value of 6.1 and 3.9, and net charge of -0.1 and -1.1 at pH 7, respectively (Table 7). In previous studies, we have shown that NDs can be loaded with peptide-lipid conjugates that were formed by modifying the N-terminus of antigen peptides with a “Cys-Ser-Ser” (CSS) linker, followed by conjugation of DOPE-MAL lipid to the thiol of Cys in the resulting peptides. Using this method, UM-41715.601 CSS-SIINFEKL (SEQ ID NO:743) and CSS-Ea were readily loaded into NDs, and the resulting NDs were stable at pH 7.4 with a single peak around 10 nm as shown by their DLS volume and intensity profiles (Tables 1 and 2). Thus, these results show that peptides with the pI values < 7 and the net charge < 0 at pH 7 (such as SIINFEKL (SEQ ID NO:770) and Ea peptides) can be modified with the CSS linker at the N-terminus for efficient loading and formation of homogenous peptide-loaded sHDL NDs. Next, we examined the impact of changing the CSS linker to CSE or CEE linker. We synthesized SIINFEKL (SEQ ID NO:770) or Ea peptides with the CSE or CEE linker (Peptides 2, 3, and 5, Table 7) and examined whether this would affect the peptide-lipid loading onto sHDL NDs. CSS-SIINFEKL (SEQ ID NO:743), CSE-SIINFEKL (SEQ ID NO:744), and CEE- SIINFEKL (SEQ ID NO:745) were synthesized and conjugated to DOPE-MAL, followed by peptide-lipid loading on to sHDL. The resulting peptide-loaded sHDL were stable at pH 7.4, and their DLS volume and intensity profiles showed similar size distributions of sHDL NDs loaded with either CSS-SIINFEKL (SEQ ID NO:743), CSE-SIINFEKL (SEQ ID NO:744), or CEE- SIINFEKL (SEQ ID NO:745) (Peptides 1, 2, and 3, FIG.1). Similarly, CSS-Ea and CSE-Ea were synthesized and conjugated to DOPE-MAL, followed by peptide-lipid loading on to sHDL. The resulting peptide-loaded sHDL were stable at pH 7.4, and their DLS volume and intensity profiles showed similar size distributions of sHDL NDs loaded with either CSS-Ea or CSE-Ea (Peptides 4 and 5, FIG.1). In addition, the loading efficiency of SIINFEKL (SEQ ID NO:770) or Ea peptides onto NDs remained similar or was slightly improved when the peptide linker was changed from CSS to either CSE or CEE (Peptides 1-5, Table 7). These results indicate that for peptides with the pI value less than 7 and the net charge less than 0 at pH 7, the CSS-, CSE-, or CEE- linker were all appropriate linkers for modifying the peptide sequences for forming homogenous peptide-loaded sHDL NDs. Example II. Synthesis of sHDL NDs carrying peptides with pI value > 7 and net charge of > 0 at pH 7. Methods Preparation of antigen-loaded sHDL NDs. DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and DOPE-MAL (N-(3- Maleimide-1-oxopropyl)-L-α-phosphatidylethanolamine) were purchased from NOF AMERICA CORPORATION. ApoA1-mimetic peptide 22A (PVLDLFRELLBELLEALKQKLK) (SEQ ID UM-41715.601 NO:769) was synthesized by GenScript Biotech. All other peptides used in the study were synthesized by Genemed Synthesis Inc. The list of antigen peptides used in this study is shown in Table 8.

[0003] 106,y.5til1 i7 b1 ul g4n -osida MreolyUta e cd n wiei x,E)4.L LH ni 7 L= H H VKSKSV V VPE E ERPF FM M M stneHV V p(ecR R SS SFFA A M PISISRMVRMRLFLFV V A A mirne Fre PSQ QSW W N N e fuqPS SRSR YT TW TVPV VPA A K K pfxeubesR Y e Y WTAPA N N W GW WTV A V Y Y eetdiW tGG DTN V D DNDKSK KEKSKEhtap ShePSCDCDSCSCDCSECSCECSCECnipsdo eshpu0seM0 05 5-1 19dim5- -88391-1- tp0383G 187G G O787 7A A O1 1eM1P P 11111V V VPRPRpni eO edh yiM M - - DLPLP- K K- K- N N- ttp-SD D- -S E E-S ETiliePSCDSD CDCSCDCSCSCECSCEC.8baetlsb raieT0 1h121314 5tDI 6 7 8 9 1 1 1 UM-41715.601 To produce blank sHDL NDs, DMPC and 22A peptide powder were mixed and hydrated in 10 mM sodium phosphate buffer (DMPC: 22A = 2 : 1, mass ratio) with pH = 7.4, which was then subjected to heating and cooling cycles to obtain blank sHDL NDs, followed by sonication for 1 min at room temperature. To load antigen peptide into blank NDs, cysteine-terminated antigen peptide was first conjugated with DOPE-MAL (antigen peptide: DOPE-MAL = 1.5 : 1, molar ratio). Then DOPE-peptide conjugate was added to blank NDs (22A: antigen peptide = 4 : 1, mass ratio) and incubated at room temperature with gentle shaking on an orbital shaker for 1 h. Unreacted antigen peptides were removed by using Zeba Spin desalting columns (Pierce). Size distribution measurement by DLS. The hydrodynamic sizes of peptide-loaded NDs were measured by dynamic light scattering (DLS, Malvern Zetasizer Nano ZSP) in 10 mM phosphate buffer (pH = 7.4). The parameter settings for refractive index (RI) and absorption were 1.45 and 0.001, respectively. Dispersant: phosphate buffer, temperature / Viscosity = 25°C / 0.89 with RI of 1.333. Method: Mark-Houwink (default setting) for size measurement. Temperature: 25°C. Equilibration time: 120 seconds. Cell Type: Disposable cuvettes ZEN0040. Measurement angle: 173 Backscatter (NIBS default). Measurement duration: automatic with 11 runs of 10 seconds for 3 measurements. Readout: size distribution by volume and intensity. Loading efficiency measurement by Liquid chromatography-mass spectrometry (LC-MS). The chromatogram of DOPE-peptides was characterized by LC-MS (Shimadzu LCMS- 2020 + LC-2040C) with a Biphenyl column (1.7 mm, 50 x 2.1 mm, 100A, Phenomenex). The mobile phase was a mixture of water, acetonitrile, and methanol. Samples were diluted 100-fold in methanol. The loading efficiencies were calculated by comparing the area under the curve (AUC) of DOPE-peptides in LC-MS chromatogram before and after the purification. Results Next, we examined how to prepare sHDL NDs loaded with peptides with pI value > 7 and net charge of > 0 at pH 7. We chose CSS-MOG38-50, CSS-PLP178-191, CSS-KV11, and CSS-NRPA7 for these studies, as they have the pI value > 7 with a net charge of > 0 at pH 7 (Table 8). In previous studies, we have shown that NDs can be loaded with peptide-lipid conjugates that were formed by modifying the N-terminus of antigen peptides with a “Cys-Ser-Ser” (CSS) linker, followed by conjugation of DOPE-MAL lipid to the thiol of Cys in the resulting peptides. UM-41715.601 This approach works well for peptides with pI < 7 with the net charge < 0 at pH 7 as shown in Example I. However, this approach often results in aggregation of NDs for peptides with poor water solubility, pI > 7, and the net charge > 0 at pH 7. This was the case for CSS-MOG38-50 peptide with the pI of 10.2 and +2 charge at pH 7 (Peptide 6, Table 8). ND loaded with CSS- MOG38-50 formed aggregates with an average size > 1000 nm in both DSL volume and intensity profiles (Peptide 6, FIG.2). Thus, we changed the CSS linker in MOG38-50 peptide to either CDD or CDDD linker, which lowered the pI value to 7.1 and 5.1 and net charge to 0 and - 1, respectively (Peptide 7 and 8, Table 8). Furthermore, changing to the CSS-linker to either CDD- or CDDD- linker increased the water solubility of MOG38-50 peptide (Peptide 6-8, Table 8). Both CDD-MOG38-50 and CDDD-MOG38-50 were loaded with sHDL NDs, forming stable and homogeneous NDs with an average size of 10 nm in 10 mM phosphate buffer at pH 7.4, as shown by the DLS volume and intensity profiles (Peptide 7 and 8, FIG.2). Moreover, the loading efficiency of CSS-MOG38-50 on NDs was significantly improved from 70.5% to 99.1% and 99.9% with the use of CDD-MOG38-50 or CDDD-MOG38-50, respectively (Peptide 6-8, FIG.2). Similarly, when sHDL NDs were loaded with CSS-PLP178-191 with poor water solubility, pI of 9.1, and net charge of 0.9 at pH 7 (Peptide 9, Table 8), this resulted in heterogenous ND size distribution (Peptide 9, FIG.2). On the other hand, CDD-PLP178-191, which has a pI value of 3.7 and net charge of -1.1 at pH 7 (Peptide 10, Table 8), exhibited improved water solubility and was stably loaded onto NDs, leading to the formation of homogeneous NDs with an average size of 10 nm in 10 mM phosphate buffer at pH 7.4, as shown by the DLS volume and intensity profiles (Peptide 10, FIG.2). The loading efficiency of CDD-PLP178-191 was also greatly increased to 96.4%, compared to 59.6% for CSS-PLP178- 191 (Peptide 9-10, FIG.2). We have also examined a similar approach for peptides with good water solubility, pI > 7, and net charge > 0 at pH 7. CSS-KV11 has a pI of 9.1 and 0.9 net charge at pH 7 with good water solubility (Peptide 11, Table 8). When sHDL NDs were loaded with CSS-KV11, the resulting NDs appeared homogeneous in DLS volume profiles; however, the DLS intensity profiles revealed aggregated NDs (Peptide 11, FIG.3). On the other hand, CSE-KV11 and CEE- KV11, which have a pI value of 6.3 and 4.5, and net charge of -0.1 and -1.1 at pH 7, respectively (Peptide 12 and 13, Table 8), were stably loaded onto NDs, leading to the formation of homogeneous NDs with an average size of 10 nm in 10 mM phosphate buffer at pH 7.4, as shown by both DLS volume and intensity profiles (Peptide 12 and 13, FIG.3). The loading UM-41715.601 efficiency of CSS-KV11, CSE-KV11, and CEE-KV11 on NDs was between 72.7% and 79.2% (Peptide 11-13, Table 8). A similar finding was observed for CSS-NRPA7, which has a pI of 9.9 and 1.9 net charge at pH 7 with good water solubility (Peptide 14, Table 8). When sHDL NDs were loaded with CSS-NRPA7, the resulting NDs appeared homogeneous in DLS volume profiles; however, the DLS intensity profiles revealed aggregated NDs (Peptide 14, FIG.3). On the other hand, CSS-NRPA7, which has a pI value of 6.4, and net charge of -0.1 at pH 7 (Peptide 15, Table 8), was stably loaded onto NDs, leading to the formation of homogeneous NDs with an average size of 10 nm in 10 mM phosphate buffer at pH 7.4, as shown by both DLS volume and intensity profiles (Peptide 15, FIG.3). The loading efficiency of CEE-NRPA7 on NDs was increased to 94.5%, compared to 80.5% for CSS-NRPA7 (Peptide 14-15, FIG.3). Overall, these results indicate that for peptides with the pI value greater than 7 and the net charge greater than 0 at pH 7, the CDD-, CDDD-, CSE-, or CEE- linkers were all appropriate linkers for modifying the peptide sequences, resulting in increased water solubility of peptides, homogenous peptide-loaded sHDL NDs, and improved loading efficiency of peptides on sHDL NDs. Example III. Synthesis of sHDL NDs carrying peptides with non-terminal cysteine. Methods Preparation of antigen-loaded sHDL NDs. DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and DOPE-MAL (N-(3- Maleimide-1-oxopropyl)-L-α-phosphatidylethanolamine) were purchased from NOF AMERICA CORPORATION. ApoA1-mimetic peptide 22A (PVLDLFRELLBELLEALKQKLK) (SEQ ID NO:769) was synthesized by GenScript Biotech. All other peptides used in the study were synthesized by Genemed Synthesis Inc. The list of antigen peptides used in this study is shown in Table 9.

[0004] 106.5yc1n7ei14cif-rMefetgn Uaiwd, a 7ol=edit % e diyctpnei yeprcif rtileitib refeaulororo oo o oht gWs P P P9ni 7erada enolgra7= wodhcth na eHp 1 1S,)N @1-.0-.3- .II4I.7el= pIp 3.5 0.3 5.0maHp(DIxr 8 9 0EefQ :.5EO75767 ni fuSN s N tbeeG Y ntaR CIImh EN irpLeGY A espoc Cxeh neV CIpIV uL LLqYLAPeVGhMeseAtLLmdi E PVPV ni0 tpVeLGL- D d1 PHSVPD esniV D uysteil di 0-0it ba32-020pt -2esp reie9:edB6- i862s 181G hThttpnG I O O D ,ePm M M D .yH H D 9ti ellibbaulTosDI617181 UM-41715.601 To produce blank sHDL NDs, DMPC and 22A peptide powder were mixed and hydrated in 10 mM sodium phosphate buffer (DMPC: 22A = 2 : 1, mass ratio) with pH = 7.4, which was then subjected to heating and cooling cycles to obtain blank sHDL NDs, followed by sonication for 1 min at room temperature. To load antigen peptide into blank NDs, cysteine-containing antigen peptide was first conjugated with DOPE-MAL (antigen peptide: DOPE-MAL = 1.5 : 1, molar ratio). Then DOPE-peptide conjugate was added to blank NDs (22A: antigen peptide = 4 : 1, mass ratio) and incubated at room temperature with gentle shaking on an orbital shaker for 1 h. Unreacted antigen peptides were removed by using Zeba Spin desalting columns (Pierce). Size distribution measurement by dynamic light scattering (DLS). The hydrodynamic sizes of peptide-loaded NDs were measured by dynamic light scattering (DLS, Malvern Zetasizer Nano ZSP) in 10 mM phosphate buffer (pH = 7.4). The parameter settings for refractive index (RI) and absorption were 1.45 and 0.001, respectively. Dispersant: phosphate buffer, temperature / Viscosity = 25°C / 0.89 with RI of 1.333. Method: Mark-Houwink (default setting) for size measurement. Temperature: 25°C. Equilibration time: 120 seconds. Cell Type: Disposable cuvettes ZEN0040. Measurement angle: 173 Backscatter (NIBS default). Measurement duration: automatic with 11 runs of 10 seconds for 3 measurements. Readout: size distribution by volume and intensity. Loading efficiency measurement by Liquid chromatography-mass spectrometry (LC-MS). The chromatogram of DOPE-peptides was characterized by LC-MS (Shimadzu LCMS- 2020 + LC-2040C) with a Biphenyl column (1.7 µm, 50 x 2.1 mm, 100A, Phenomenex). The mobile phase was a mixture of water, acetonitrile, and methanol. Samples were diluted 100-fold in methanol. The loading efficiencies were calculated by comparing the area under the curve (AUC) of DOPE-peptides in LC-MS chromatogram before and after the purification. Results We examined how to prepare sHDL NDs loaded with peptides containing non-terminal cysteine residues. We chose mIns2 B:9-23 and HMOG186-200 for these studies, and they have the pI value < 7 with a net charge of < 0 at pH 7 (Peptide 16 and 17, Table 9). When sHDL NDs were loaded with mIns2 B:9-23 with poor water solubility, pI of 5.3, and net charge of -1.0 at pH 7 (Peptide 16, Table 9), this resulted in heterogeneous ND size UM-41715.601 distribution (Peptide 16, FIG.4). Similarly, HMOG186-200, which has a pI of 3.0 and a net charge of -0.1 at pH 7 (Peptide 17, Table 9), resulted in a heterogeneous and size distribution (Peptide 17, FIG.4) when loaded into sHDL NDs. To address this issue, we modified HMOG186-200 by adding a DDD linker (Asp-Asp-Asp) to its N-terminus, resulting in HMOG186-200-DDD, which had a pI of 0.5 and a net charge of -3.1 at pH 7 (Peptide 18, FIG. 2). This modification significantly improved the stability and water solubility of the peptide. The HMOG186-200-DDD-loaded NDs were stable at pH 7.4, with a single peak around 10 nm in their DLS volume and intensity profiles (FIG.4). The loading efficiency of HMOG186-200- DDD on NDs was also improved to 82.4%, compared to 68.9% for HMOG186-200 (Peptides 17-18, Table 9).These results demonstrate versatility in using peptides with cysteine residues not only at the N-terminus but also at non-terminal positions. The inclusion of a linker enhances the water solubility of these peptides, facilitates the formation of homogeneous peptide-loaded sHDL NDs, and improves the loading efficiency of peptides onto sHDL NDs. Example IV. Synthesis of sHDL NDs carrying peptides with C-terminal cysteine. Methods Preparation of antigen-loaded sHDL NDs. DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and DOPE-MAL (N-(3- Maleimide-1-oxopropyl)-L-α-phosphatidylethanolamine) were purchased from NOF AMERICA CORPORATION. ApoA1-mimetic peptide 22A (PVLDLFRELLBELLEALKQKLK) (SEQ ID NO:769) was synthesized by GenScript Biotech. All other peptides used in the study were synthesized by Genemed Synthesis Inc. The list of antigen peptides used in this study is shown in Table 10.

[0005] 106,.y5ti1l7ib14ul-osMrUetaywcn ,7ei=ciffe rt dceNiboHle LatnapelbatoSn @SsD i,Hsecont yenrtilu oetibqdes eaul ro WosoPedadioltpne7e= ep hgrHsw titeap 1.02eycNhc@ -8raneincifI1wofe p.6hS g.niDIVIda Q :.1O67eolESN lp dmanax,E)4–.C ni 7Q=PstneH epcQP(neY Pmiruq Lreef pfesEPxeQeubdi PF)2eettap PeQH ht h P LN(nipsdo eshpu e M ditm p0 1e1p e C-n enidit ihp da Tyt.i illePG 0i1baetlsb raieThtDI91 UM-41715.601 To produce blank sHDL NDs, DMPC and 22A peptide powder were mixed and hydrated in 10 mM sodium phosphate buffer (DMPC: 22A = 2 : 1, mass ratio) with pH = 7.4, which was then subjected to heating and cooling cycles to obtain blank sHDL NDs, followed by sonication for 1 min at room temperature. To load antigen peptide into blank NDs, cysteine-C-terminated antigen peptide was first conjugated with DOPE-MAL (antigen peptide: DOPE-MAL = 1.5 : 1, molar ratio). Then DOPE-peptide conjugate was added to blank NDs (22A: antigen peptide = 4 : 1, mass ratio) and incubated at room temperature with gentle shaking on an orbital shaker for 1 h. Unreacted antigen peptides were removed by using Zeba Spin desalting columns (Pierce). Size distribution measurement by DLS. The hydrodynamic sizes of peptide-loaded NDs were measured by dynamic light scattering (DLS, Malvern Zetasizer Nano ZSP) in 10 mM phosphate buffer (pH = 7.4). The parameter settings for refractive index (RI) and absorption were 1.45 and 0.001, respectively. Dispersant: phosphate buffer, temperature / Viscosity = 25°C / 0.89 with RI of 1.333. Method: Mark-Houwink (default setting) for size measurement. Temperature: 25°C. Equilibration time: 120 seconds. Cell Type: Disposable cuvettes ZEN0040. Measurement angle: 173 Backscatter (NIBS default). Measurement duration: automatic with 11 runs of 10 seconds for 3 measurements. Readout: size distribution by volume and intensity. Loading efficiency measurement by LC-MS. The chromatogram of DOPE-peptides was characterized by LC-MS (Shimadzu LCMS- 2020 + LC-2040C) with a Biphenyl column (1.7 µm, 50 x 2.1 mm, 100A, Phenomenex). The mobile phase was a mixture of water, acetonitrile, and methanol. Samples were diluted 100-fold in methanol. The loading efficiencies were calculated by comparing the area under the curve (AUC) of DOPE-peptides in LC-MS chromatogram before and after the purification. Results Next, we examined how to prepare sHDL NDs loaded with peptides containing C- terminal cysteine residues. We chose Gliadin-C1 for these studies, which has a pI of 6.1 and a net charge of -0.1 at pH 7 (Peptide 19, Table 10). When sHDL NDs were loaded with Gliadin-C1, the resulting NDs were stable at pH 7.4, with a single peak around 10 nm in their DLS volume and intensity profiles (Peptide 19, FIG.5). The loading efficiency of Gliadin-C1 on NDs was 88.9% (Table 10). UM-41715.601 These results indicate that for peptides containing C-terminal cysteine residues, stable peptide-loaded sHDL NDs can also be obtained. EQUIVALENTS The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein. INCORPORATION BY REFERENCE The entire disclosure of each of the patent documents and scientific articles referred to herein is incorporated by reference for all purposes. The following references are herein incorporated by reference in their entireties: 1. Wang, L., Wang, N., Zhang, W. et al. 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Biomacromolecules.2014 Apr 14;15(4):1097-114. doi: 10.1021 / bm500169p. Epub 2014 Mar 24. PMID: 24661025. 10. Braun K, Pochert A, Lindén M, Davoudi M, Schmidtchen A, Nordström R, Malmsten M. Membrane interactions of mesoporous silica nanoparticles as carriers of antimicrobial peptides. J Colloid Interface Sci.2016 Aug 1;475:161-170. doi: 10.1016 / j.jcis.2016.05.002. Epub 2016 May 5. PMID: 27174622. 11. Akishiba M, Takeuchi T, Kawaguchi Y, Sakamoto K, Yu HH, Nakase I, Takatani-Nakase T, Madani F, Gräslund A, Futaki S. Cytosolic antibody delivery by lipid-sensitive endosomolytic peptide. Nat Chem.2017 Aug;9(8):751-761. doi: 10.1038 / nchem.2779. Epub 2017 May 22. PMID: 28754944. 12. Chen SY, Xu XX, Li X, Yi NB, Li SZ, Xiang XC, Cheng DB, Sun T. Recent advances in the intracellular delivery of macromolecule therapeutics. Biomater Sci.2022 Nov 22;10(23):6642- 6655. doi: 10.1039 / d2bm01348g. PMID: 36214257. 13. Gasparini G, Bang EK, Montenegro J, Matile S. Cellular uptake: lessons from supramolecular organic chemistry. Chem Commun (Camb).2015 Jul 4;51(52):10389-402. doi: 10.1039 / c5cc03472h. PMID: 26030211. 14. Lau WL, Ege DS, Lear JD, Hammer DA, DeGrado WF. Oligomerization of fusogenic peptides promotes membrane fusion by enhancing membrane destabilization. Biophys J.2004 Jan;86(1 Pt 1):272-84. doi: 10.1016 / S0006-3495(04)74103-X. PMID: 14695269; PMCID: PMC1303790. 15. Mousavizadeh A, Jabbari A, Akrami M, Bardania H. Cell targeting peptides as smart ligands for targeting of therapeutic or diagnostic agents: a systematic review. Colloids Surf B Biointerfaces.2017 Oct 1;158:507-517. doi: 10.1016 / j.colsurfb.2017.07.012. Epub 2017 Jul 13. PMID: 28738290. UM-41715.601 16. Ren L, Gao Y, Cheng Y. A manganese (II)-based coordinative dendrimer with robust efficiency in intracellular peptide delivery. Bioact Mater.2021 Aug 11;9:44-53. doi: 10.1016 / j.bioactmat.2021.08.006. PMID: 34820554; PMCID: PMC8586439. 17. 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High-Density Lipoprotein- Mimicking NDss for Chemo-immunotherapy against Glioblastoma Multiforme. ACS Nano. 2019 Feb 26;13(2):1365-1384. doi: 10.1021 / acsnano.8b06842. Epub 2019 Feb 11. PMID: 30721028; PMCID: PMC6484828. 21.7. Zhang Z, Chen J, Ding L, Jin H, Lovell JF, Corbin IR, Cao W, Lo PC, Yang M, Tsao MS, Luo Q, Zheng G. HDL-mimicking peptide-lipid nanoparticles with improved tumor targeting. Small.2010 Feb 5;6(3):430-7. doi: 10.1002 / smll.200901515. PMID: 19957284. 22. Aikins ME, Xu C, Moon JJ. Engineered Nanoparticles for Cancer Vaccination and Immunotherapy. Acc Chem Res.2020 Oct 20;53(10):2094-2105. doi: 10.1021 / acs.accounts.0c00456. Epub 2020 Oct 5. PMID: 33017150; PMCID: PMC7871038. 23. Kuai R, Ochyl LJ, Bahjat KS, Schwendeman A, Moon JJ. Designer vaccine NDss for personalized cancer immunotherapy. Nat Mater.2017 Apr;16(4):489-496. doi: 10.1038 / nmat4822. Epub 2016 Dec 26. PMID: 28024156; PMCID: PMC5374005. 24. Kuai R, Sun X, Yuan W, Xu Y, Schwendeman A, Moon JJ. Subcutaneous NDs Vaccination with Neoantigens for Combination Cancer Immunotherapy. Bioconjug Chem.2018 Mar 21;29(3):771-775. doi: 10.1021 / acs.bioconjchem.7b00761. Epub 2018 Feb 27. PMID: 29485848; PMCID: PMC6080626. 25. Aikins ME, Qin Y, Dobson HE, Najafabadi AH, Lyu K, Xu Y, Xin Y, Schwendeman A, Wicha MS, Chang AE, Li Q, Moon JJ. Cancer stem cell antigen NDs cocktail elicits anti-tumor UM-41715.601 immune responses in melanoma. J Control Release.2022 Nov;351:872-882. doi: 10.1016 / j.jconrel.2022.09.061. Epub 2022 Oct 10. PMID: 36206945; PMCID: PMC9765445. 26. Scheetz L, Kadiyala P, Sun X, Son S, Hassani Najafabadi A, Aikins M, Lowenstein PR, Schwendeman A, Castro MG, Moon JJ. Synthetic High-density Lipoprotein NDss for Personalized Immunotherapy Against Gliomas. Clin Cancer Res.2020 Aug 15;26(16):4369- 4380. doi: 10.1158 / 1078-0432.CCR-20-0341. Epub 2020 May 21. PMID: 32439701; PMCID: PMC7442596. 27. 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Claims

UM-41715.601 CLAIMS 1. A composition comprising an sHDL nanoparticle comprising a phospholipid; an apoplipoprotein mimetic; a thiol-reactive lipid; and a peptide comprising a linker moiety connected with a payload moiety, wherein the linker comprises either: cysteine (C) and optionally one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S), or D-D or D-D-D if the payload includes a C amino acid; wherein the payload comprises a polypeptide that is 5 to 35 amino acids in length, and wherein the peptide comprises a net negative charge at a pH of 7 and an isoelectric point of 0.4 to 12; and wherein the peptide is covalently attached to the thiol-reactive lipid by way of the linker.

2. The composition of claim 1, wherein the linker comprises cysteine (C) and optionally one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S), wherein the peptide is covalently attached to the thiol-reactive lipid by way of the amino terminus of the Cys, the carboxy terminus of the Cys, or a non-terminal position of the Cys.

3. The composition of claim 1, wherein the payload comprises a C amino acid; wherein the linker comprises DD or DDD; wherein the peptide is covalently attached to the thiol-reactive lipid by way of the D-D or D-D-D of the linker.

4. The composition of claim 1, wherein the peptide comprises the formula: [linker]- [payload] or [payload]-[linker].UM-41715.601 5. The composition of claim 1, wherein the linker sequence is selected from: C, DDCDD, DD, and DDD if the payload comprises a C amino acid.

6. The composition of claim 1, wherein the payload has a net positive charge at a pH of 7 to 12.

7. The composition of claim 1, wherein the payload has a net zero charge at a pH of 7 to 12.

8. The composition of claim 1, wherein the payload has a net negative charge at a pH of 7 to 12.

9. The composition of claim 1, wherein the peptide has a charge of less than -0.

1.

10. The composition of claim 1, wherein the peptide has a charge ranging from -0.1 to -5.

0.

11. The composition of claim 1, wherein the peptide comprises an isoelectric point of 3.7 to 12.

12. The composition of claim 1, wherein the peptide comprises an isoelectric point of 0.62 to 9.

78.

13. The composition of claim 1, wherein the linker comprises a peptide dimer.

14. The composition of claim 1, wherein the peptide dimer is selected from DD, SE, SD, and EE.

15. The composition of claim 1, wherein the one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S) comprises a peptide trimer.

16. The composition of claim 15, wherein the peptide trimer is selected from DDD, EEE, and KEE.

17. The composition of claim 1, wherein the one to five amino acids independently selected from aspartic acid (D), glutamic acid (E), and serine (S) comprises a peptide 4-mer.UM-41715.601 18. The composition of claim 17, wherein the peptide 4-mer is selected from DDDD (SEQ ID NO:762) and EEEE (SEQ ID NO:763).

19. The composition of claim 1, wherein the payload has a charge of greater than 0.1 at pH 7.

20. The composition of claim 19, wherein the payload has a charge ranging from 0.1 to 5.

0.

21. The composition of claim 1, wherein the payload is a polypeptide that is 12 to 35 amino acids in length.

22. The composition of claim 21, wherein the payload is selected from GWYRSPFSRVVHL (SEQ ID NO:764), NTWTTSQSIAFPSK (SEQ ID NO:765), KVAPVWVRMME (SEQ ID NO:766), KYNKANAFL (SEQ ID NO:767), and ASFEAQGALANIAVDKA (SEQ ID NO:768).

23. The composition of claim 1, wherein the apolipoprotein mimetic is an ApoA-I mimetic, having a sequence of any of SEQ ID NOs: 1-336 and WDRVKDLATVYVDVLKDSGRDYVSQF (SEQ ID NO:341), LKLLDNWDSVTSTFSKLREOL (SEQ ID NO:342), PVTOEFWDNLEKETEGLROEMS (SEQ ID NO:343), KDLEEVKAKVQ (SEQ ID NO: 344), KDLEEVKAKVO (SEQ ID NO: 345), PYLDDFQKKWQEEMELYRQKVE (SEQ ID NO: 346), PLRAELQEGARQKLHELOEKLS (SEQ ID NO: 347), PLGEEMRDRARAHVDALRTHLA (SEQ ID NO: 348), PYSDELRQRLAARLEALKENGG (SEQ ID NO: 349), ARLAEYHAKATEHLSTLSEKAK (SEQ ID NO: 350), PALEDLROGLL (SEQ ID NO: 351), PVLESFKVSFLSALEEYTKKLN (SEQ ID NO:352), PVLESFVSFLSALEEYTKKLN (SEQ ID NO:353), PVLESFKVSFLSALEEYTKKLN (SEQ ID NO:352), TVLLLTICSLEGALVRRQAKEPCV (SEQ ID NO: 354) QTVTDYGKDLME (SEQ ID NO:355), KVKSPELOAEAKSYFEKSKE (SEQ ID NO:356), VLTLALVAVAGARAEVSADOVATV (SEQ ID NO:357), NNAKEAVEHLOKSELTOOLNAL (SEQ ID NO:358), LPVLVWLSIVLEGPAPAOGTPDVSS (SEQ ID NO:359), LPVLVVVLSIVLEGPAPAQGTPDVSS (SEQ ID NO:360), ALDKLKEFGNTLEDKARELISUM-41715.601 (SEQ ID NO: 361), VVALLALLASARASEAEDASLL (SEQ ID NO:362), HLRKLRKRLLRDADDLQKRLAVYOA (SEQ ID NO:363), AQAWGERLRARMEEMGSRTRDR (SEQ ID NO:364), LDEVKEQVAEVRAKLEEQAQ (SEQ ID NO:365), DWLKAFYDKVAEKLKEAF (SEQ ID NO:236), DWLKAFYDKVAEKLKEAFPDWAKAAYDKAAEKAKEAA (SEQ ID NO:366), PVLDLFRELLNELLEALKQKL (SEQ ID NO:367), PVLDLFRELLNELLEALKQKLA (SEQ ID NO:368), PVLDLFRELLNELLEALKQKLK (SEQ ID NO:4), PVLDLFRELLNELLEALKQKLA (SEQ ID NO:369), PVLDLFRELLNELLEALKKLLK (SEQ ID NO:370), PVLDLFRELLNELLEALKKLLA (SEQ ID NO:371), PLLDLFRELLNELLEALKKLLA (SEQ ID NO:372), and EVRSKLEEWFAAFREFAEEFLARLKS (SEQ ID NO: 373).

24. The composition of claim 23, wherein the apolipoprotein mimetic has the sequence PVLDLFRELLNELLEALKQKLK (SEQ ID NO: 4).

25. The composition of claim 1, wherein the thiol-reactive lipid is selected from dioleoyl- sn-glycero-3-phosphoethanolamine-N-[3-(2-pyridyldithio) propionate] (DOPE-PDP), 1,2-di- (9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidophenyl)butyramide], 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidophenyl)butyramide], 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidomethyl)cyclohexane- carboxamide], 1,2-Dioleoyl-sn–glycero-3-phosphoethanolamine-maleimide (DOPE-Mal), and 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine-N-[4-(p- maleimidomethyl)cyclohexane-carboxamide].

26. The composition of claim 25, wherein the thiol-reactive lipid is DOPE-PDP.

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