Vaccine adjuvants and formulations thereof

Abstract

The present disclosure pertains to the field of vaccine technologies, with a focus on improved vaccine adjuvants and their formulations for enhancing immune responses. The described approach addresses limitations of traditional adjuvants by introducing novel formulations of the TLR7 agonist 1 V270, either as a standalone agent or in combination with co-adjuvants such as 2G272 and 2E151. These formulations include self-assembling nanoparticles, lipid-incorporated nanoparticles, and aqueous or liposomal combinations, designed to enhance antigen-specific immune responses while maintaining favorable safety and stability profiles. Notable advantages include balanced Thl / Th2 immune responses, dose¬ sparing effects, cross-reactive immunity, and compatibility with modern vaccine platforms such as mRNA vaccines. Applications encompass systemic and mucosal immunization against a wide range of pathogens, including influenza, SARS-CoV-2, and other infectious diseases. The described approach demonstrates enhanced immunogenicity, durability, and efficacy, particularly in aged populations and those requiring heterologous prime-boost regimens.

Description

[0001] 1133.122WO1, SD2025-069-2PCT VACCINE ADJUVANTS AND FORMULATIONS THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application Serial No. 63 / 708,026 titled “Improved Vaccine Adjuvants and Formulations Thereof,” filed October 16, 2024, the disclosure of which is incorporated herein in its entirety by reference. STATEMENT OF GOVERNMENT SUPPORT This invention was made with government support under 75N93019C00042, HHSN272200900034c, and HHSN272201400051c awarded by the National Institutes of Health. The Government has certain rights in the invention. FIELD OF DISCLOSURE The present disclosure pertains to vaccine technologies, specifically to improved vaccine adjuvants and their formulations for enhancing immune responses. BACKGROUND Vaccination represents one of the most effective means to prevent infectious disease and reduce morbidity and mortality worldwide. In recent decades, advances in immunobiology and vaccine platforms have highlighted the importance of adjuvants—substances that augment and direct immune responses to co-administered antigens. Traditional adjuvant classes, including aluminum salts, oil-in-water emulsions, and microbial-derived immunostimulants, have been employed to generate strong and durable antibody responses. The evolution of subunit vaccines, inactivated viruses, and nucleic acid modalities underscores the need for adjuvants capable of meeting diverse formulation requirements while maintaining favorable safety and stability profiles. Vaccines seek to elicit balanced and durable humoral and cellular immunity capable of preventing infection or disease progression. In particular, robust T helper type 1 (Th1) responses can support cell-mediated effector functions against intracellular pathogens, while T helper type 2 (Th2) pathways drive potent antibody production and class switching. Mucosal immunization strategies aim to generate secretory IgA at barrier surfaces to block initial infection. At the same time, modern platforms such as mRNA and viral vectors require adjuvants that integrate seamlessly to enhance antigen expression and presentation. Dose- sparing capabilities, cross-protective breadth against evolving strains, and long-lasting memory responses remain defining goals for next-generation vaccine formulations. Despite significant successes, currently available adjuvants exhibit limitations in potency, reactogenicity, or immune profile specificity. Aluminum salts, while well 1133.122WO1, SD2025-069-2PCT characterized and safe, tend to favor Th2 polarization and may not adequately support Th1- biased or cellular responses. Emulsion-based systems can improve immunogenicity, but occasionally induce excessive local inflammation and pose manufacturing and stability challenges. Microbial-derived agonists, such as toll-like receptor ligands, have shown promise but can suffer from narrow safety windows or limited compatibility with certain antigens and platforms. Furthermore, achieving balanced systemic and mucosal immunity often requires complex formulation strategies that complicate manufacturing and regulatory pathways. SUMMARY In one embodiment, the disclosure includes an immunogenic or vaccine adjuvant composition comprising self-assembled nanoparticles of Formula (I), lipid-incorporated Formula (I) nanoparticles or liposomal or non-liposomal nanoparticles such as aqueous dispersions, aqueous suspensions or emulsions. Formula (I) comprises a moiety in which X1is O, S or NRc; R1is hydrogen, C1–C10alkyl (substituted or unsubstituted), C6–C10aryl (substituted or unsubstituted) or C5–C9heterocyclic (substituted or unsubstituted); Rcis hydrogen, C1–C10alkyl (substituted or unsubstituted) or together with R1forms a (substituted) heterocyclic ring; each R2independently is OH, C1–C6alkyl (substituted or unsubstituted), C1– C6alkoxy (substituted or unsubstituted), C(O)-alkyl, C(O)-aryl, C(O)OH, C(O)O-alkyl, NRaRb, C(O)NRaRb, halo, nitro or cyano, or R2is absent; each Raand Rbindependently is hydrogen, C1–C6alkyl (substituted or unsubstituted), C3–C8cycloalkyl, C1–C6alkoxy, C1–C6alkanoyl, aryl, Het or combinations thereof; substituents on any alkyl, aryl or heterocyclic group include hydroxy, alkyl, hydroxyalkylene, alkoxy, cycloalkyl, alkoxyalkylene, amino, cyano, halo or aryl; n is 0–4; X2is a bond or linking group; and R3is a phospholipid or analog comprising one or two alkyl ethers or carboxylic esters of the glyceryl moiety; or tautomers, pharmaceutically acceptable salts or solvates thereof. The composition further comprises a co- adjuvant and / or an antigen. In another embodiment, R3comprises a group of formula in which R11and R12are C8– C25acyl groups; R13is hydrogen or a negative charge; R14is a C1–C8alkyl (optionally substituted or bearing NH, S or O); Z is O and q is 1. X2is —C(O)— and X1is O. Each acyl group may include one to four sites of unsaturation, epoxidation or hydroxylation. The nanoparticles have a Z-average of about 20–200, a polydispersity index less than 0.4 and an average zeta potential between –50 mV and 50 mV. These compositions may include or exclude lipids selected from phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, phosphatidylglycerol, DOTAP, DOPC, DOPG, DSPC, PEG-phospholipids, cholesterol, ionizable lipids or combinations thereof; surfactants such as 1133.122WO1, SD2025-069-2PCT Cremophor EL, Tween-80, Tween-20, SPAN-80, SPAN-83, poloxamers, TPGS, SDS, methylcellulose, PEG400 or glycerol; and oils such as squalene, soybean oil, castor oil, mineral oil, vegetable oil, sesame seed oil or linseed oil. The antigen may be a nucleic acid, an amino acid sequence / protein, a carbohydrate or an inactivated, dead or attenuated virus or bacteria, including cancer, viral or bacterial proteins or carbohydrates derived from pathogens such as Dengue, West Nile, Zika, SARS-CoV, SARS-CoV-2, influenza, HIV, tuberculosis, cholera, salmonella, pertussis, malaria or syphilis. An additional adjuvant may include aluminum salts, MPL, squalene-in-water emulsions, CpG 1018, AS04, AS01, QS21 or AS03. The co-adjuvant may be formulated as nanoparticles of Formula (II), (III), (IV), (V), (VI) or (VII), or as tautomers, salts or solvates thereof. In further embodiments, the composition is formulated as a nanoparticle, a micelle, an emulsion or an aqueous dispersion / suspension; as a neutral or charged formulation; as a co- encapsulated formulation in which Formula (I) and the co-adjuvant are co-encapsulated within a single nanoparticle; or as an admixed composition of separate nanoparticles or as an aqueous admix of Formula (I) with Formula (II) through (VII). In another embodiment, the disclosure includes a method to produce an immune response in a subject comprising administering an effective amount of the composition. The method may enhance or prolong an antigen immune response or boost a primary vaccination. Administration may be intramuscular, subcutaneous or intradermal. The liposomal formulation of 1V270 (Lipo-1V270) reduces its innate immune stimulatory potency but enhances its ability to induce antigen-specific immune responses in vivo, including: increased IgG2a and IgG1 antibodies; dose-dependent adjuvant effects; in the heterologous prime-boost with MPLA- and Lipo-1V270-adjuvanted IIAV, Lipo-1V270 boosting provides the following protective immune responses; induction of HA-specific IgG and IgA in nasal wash and bronchial alveolar lavage; comparable IgG responses to MPLA prime-boost vaccination; HA-specific IgG2a and splenic T-cell responses; cross-reactive Ig responses; Lipo-1V270 shows dose-sparing effects when used with mRNA antigen. These and other features will be more clearly understood from the following detailed description and accompanying drawings and claims. BRIEF DESCRIPTION OF THE DRAWINGS In the drawings, which are not necessarily drawn to scale, like numerals describe substantially similar components throughout the several views. Like numerals having different letter suffixes represent different instances of substantially similar components. The drawings 1133.122WO1, SD2025-069-2PCT illustrate generally, by way of example, but not by way of limitation, various embodiments of the present invention. FIGS. 1A-1D demonstrate the in vitro innate immune stimulatory effects of Lipo- 1V270 adjuvant and unformulated IV270, in accordance with various embodiments. FIGS. 2A-2F demonstrate that Lipo-1V270 sustains a Th1 response while increasing antigen specific IgG1, in accordance with various embodiments. FIG. 3 provides an experimental timeline demonstrating the dosing schedule for a heterologous prime-boost regimen of IIVA + MPLA + Lipo-1V270 immunization, in accordance with various embodiments. FIGS. 4A-4F demonstrate that intramuscular and intranasal Lipo-1V270 boosting induces HA-specific IgG and IgA in nasal wash and bronchoalveolar lavage fluid (BALF), in accordance with various embodiments. FIGS.5A-5I demonstrate Lipo-1V270 adjuvanted IIAV vaccine induces systemic and local antigen specific IgG, IgA, and splenic T cell responses, in accordance with various embodiments. FIGS.6A-6C demonstrate intranasal boosting with Lipo-1V270 induces mucosal IgA and superior antigen-specific IgG2a induction, in accordance with various embodiments. FIGS. 7A-7D demonstrate heterologous reactive IgG induction by Lipo-1V270, in accordance with various embodiments. FIGS. 8A-8E demonstrate the adjuvant screening process for an mRNA antigen application, in accordance with various embodiments. FIG.8F shows Lipo-1V270 enhances mRNA vaccine immunogenicity, in accordance with various embodiments. FIG. 9 illustrates the different types of formulations prepared with TLR4 agonist compounds 2G023A and 2G053, in accordance with various embodiments. FIG. 10 provides the biophysical characteristics of liposomal formulations of 1V270 and in combination with 2G023A, in accordance with various embodiments. FIG.11 provides the biophysical characteristics of aqueous formulations of 1V270 and in combination with 2G023A, in accordance with various embodiments. FIG. 12 provides the biophysical characteristics of aqueous admix, aqueous combination, liposomal admix, and liposomal combination formulations of 1V270-2G023A co-adjuvants, in accordance with various embodiments. FIG.13 demonstrates the effects of 1V270-2G023A co-adjuvancy formulation on IgG1 antibody titers, in accordance with various embodiments. 1133.122WO1, SD2025-069-2PCT FIG.14 demonstrates the effects of 1V270-2G023A co-adjuvancy formulation on IgG2 antibody titers, in accordance with various embodiments. FIGS.15A-15C demonstrate the effects of 1V270-2G023A co-adjuvancy formulation on HA-specific IgG antibody titers in aged mice after immunization with HA + 1V270- 2G023A, in accordance with various embodiments. FIGS.16A-16C demonstrate the effects of 1V270-2G023A co-adjuvancy formulation on lymphoid cell populations in aged mice after immunization with HA + 1V270-2G023A, in accordance with various embodiments. FIG.17 shows the combination of 1V270 with 2E151 synergistically enhances 1V270- induced innate immune responses, in accordance with various embodiments. FIGS. 18A-18C show that 2E151 acts as a co-adjuvant to 1V270 when included in a boosted intramuscular immunization regimen with OVA antigen, in accordance with various embodiments. FIGS. 19A-19C demonstrate that 2E151 + 1V270 co-adjuvancy improves immunogenicity via HA-specific IgG antibody generation in aged mice after a boosted intramuscular immunization regimen with HA antigen, in accordance with various embodiments. FIGS. 20A-20C demonstrate that 2E151 + 1V270 co-adjuvancy improves immunogenicity via expansion of lymphoid cell populations in aged mice after being administered a boosted intramuscular immunization regimen with HA antigen, in accordance with various embodiments. FIGS. 21A-21E demonstrates that 2G272 works as a co-adjuvant with 1V270 when included in a boosted immunization regimen with IIAV, in accordance with various embodiments. FIGS.22A-22F demonstrates 1V270-2G272 co-adjuvancy promotes a germinal center reaction in the lymphoid organs of mice administered a boosted immunization regimen with IIAV, in accordance with various embodiments. FIGS. 23A-23E demonstrates 1V270-2G272 co-adjuvancy elicits the generation of cross-reactive anti-HA antibodies (from a phylogenetically distant influenza strain) after a boosted immunization regimen with IIAV, in accordance with various embodiments. FIGS. 24A-24D demonstrating that various Influenza strains induced IgG, IFN- gamma, and IL-17 responses in lymphoid cells from mice administered 1V270-2G272 co- adjuvants with IIAV during an immunization regimen, in accordance with various embodiments. 1133.122WO1, SD2025-069-2PCT FIGS.25A-25F show that Influenza strains induced IgG and IFN-gamma responses in lymphoid cells from aged mice administered 1V270-2G272 co-adjuvants with IIAV during an immunization regimen, in accordance with various embodiments. DESCRIPTION Reference will now be made in detail to certain embodiments of the disclosed subject matter. While the disclosed subject matter will be described in conjunction with the enumerated claims, it will be understood that the exemplified subject matter is not intended to limit the claims to the disclosed subject matter. Vaccination has long been recognized as one of the most effective strategies for preventing infectious diseases and reducing global morbidity and mortality. However, the development of next-generation vaccines has revealed significant limitations in conventional adjuvant technologies. Traditional adjuvants, such as aluminum salts, oil-in-water emulsions, and microbial-derived immunostimulants, often fail to achieve the desired balance between humoral and cellular immune responses. For instance, aluminum salts predominantly favor T helper type 2 (Th2) polarization, which is insufficient for combating intracellular pathogens requiring robust T helper type 1 (Th1) responses. Similarly, while emulsion-based systems can enhance immunogenicity, they frequently induce excessive local inflammation and pose challenges related to manufacturing and stability. Microbial-derived agonists, such as toll-like receptor (TLR) ligands, have shown promise but are often constrained by narrow safety windows, limited compatibility with certain antigens, and suboptimal integration with modern vaccine platforms, such as mRNA and viral vectors. Furthermore, achieving balanced systemic and mucosal immunity often necessitates complex formulation strategies, complicating manufacturing and regulatory pathways. The present disclosure addresses these limitations by introducing novel vaccine adjuvants and formulations that leverage the distinct properties of the TLR7 agonist 1V270, either as a standalone agent or in combination with co-adjuvants such as 2G272 and 2E151. These formulations include self-assembling nanoparticles, lipid-incorporated nanoparticles, and aqueous or liposomal combinations, which are specifically designed to enhance antigen- specific immune responses while maintaining favorable safety and stability profiles. For example, liposomal formulations of 1V270 reduce innate immune stimulatory potency, but significantly enhance antigen-specific immune responses in vivo, including increased IgG2a and IgG1 antibody production, dose-sparing effects, and cross-reactive immune responses. Additionally, co-adjuvancy systems, such as 1V270-2G272 and 1V270-2E151, provide synergistic benefits by promoting balanced Th1 / Th2 immune responses, expanding lymphoid 1133.122WO1, SD2025-069-2PCT cell populations, and inducing durable and cross-protective immunity against phylogenetically distant strains of pathogens. The described formulations offer significant benefits for contemporary vaccine platforms, such as mRNA vaccines, where compatibility with lipid nanoparticles and dose- sparing capabilities are of high importance. By refining the adjuvant properties of 1V270 and its co-adjuvants, these formulations facilitate the creation of vaccines that are not only more effective but also safer and simpler to produce. These improvements address pressing medical needs, such as enhancing mucosal immunity, providing cross-reactive protection against rapidly mutating RNA viruses, and improving vaccine efficacy in populations with pre-existing immunity or advanced age. Definitions The following definitions are included to provide a clear and consistent understanding of the specification and claims. As used herein, the recited terms have the following meanings. All other terms and phrases used in this specification have their ordinary meanings as one of skill in the art would understand. Such ordinary meanings may be obtained by reference to technical dictionaries, such as Hawley's Condensed Chemical Dictionary 16th Edition, by M. Larranga, R Lewis Sr., and R Lewis, New York, N.Y., 2016. An “acyl” group as the term is used herein refers to an organic structure bearing a carbonyl group through which the structure is bonded, e.g., to glycerol hydroxyl groups of a phospholipid, forming a “carboxylic ester” group. Examples of acyl groups include fatty acid groups such as oleoyl groups, that thus form fatty (e.g., oleoyl) esters with the glycerol hydroxyl groups. An “alkyl” group includes straight or branched C8-24alkyl groups which may be substituted. Alkyl includes straight or branched C1-10alkyl groups, e.g., methyl, ethyl, propyl, butyl, pentyl, isopropyl, isobutyl, 1-methylpropyl, 3-methylbutyl, hexyl, and the like. Lower alkyl includes straight or branched C1-6alkyl groups, e.g., methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1- methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2- dimethylpropyl, and the like. A “heteroalkyl” group is an alkyl group wherein one or more carbon atoms is replaced with a heteroatom (e.g., O, NH, and S). Polyethylene glycol (PEG) is an example of a heteroalkyl group. The term “alkylene” refers to a divalent straight or branched hydrocarbon chain (e.g., ethylene: -CH2=CH2-) comprising at least one double bond. 1133.122WO1, SD2025-069-2PCT The term “heteroalkylene” is an alkylene group wherein one or more carbon atoms is replaced with a heteroatom (e.g., O, NH, and S). The group -O-CH2CH=CH2is an example of a heteroalkylene. The term “alkynyl” refers to a divalent straight or branched hydrocarbon chain (e.g., ethylene: -C≡CH and -C≡C-) comprising at least one triple bond. Cycloalkyl, such as C3-7cycloalkyl, includes groups such as, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like, and alkyl-substituted C3-7cycloalkyl group, e.g., straight or branched C1-6alkyl group such as methyl, ethyl, propyl, butyl or pentyl, and C6-7cycloalkyl group such as, cyclopentyl or cyclohexyl, and the like. Heterocycloalkyl, such as C3-7heterocycloalkyl, includes groups such as tetrahydrofuranyl, pyrrolidinyl, morpholinyl, piperidinyl, and piperazinyl. Lower alkoxy includes C1-6alkoxy groups, such as methoxy, ethoxy or propoxy, and the like. Lower alkanoyl includes C1-6alkanoyl groups, such as formyl, acetyl, propanoyl, butanoyl, pentanoyl or hexanoyl, and the like. C7-11aroyl, includes groups such as benzoyl or naphthoyl; Lower alkoxycarbonyl includes C2-7alkoxycarbonyl groups, such as methoxycarbonyl, ethoxycarbonyl or propoxycarbonyl, and the like. Lower alkylamino group means amino group substituted by C1-6alkyl group, such as, methylamino, ethylamino, propylamino, butylamino, and the like. Di(lower alkyl)amino group means amino group substituted by the same or different and C1-6alkyl group (e.g., dimethylamino, diethylamino, ethylmethylamino). Lower alkylcarbamoyl group means carbamoyl group substituted by C1-6alkyl group (e.g., methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, butylcarbamoyl). Di(lower alkyl)carbamoyl group means carbamoyl group substituted by the same or different and C1-6alkyl group (e.g., dimethylcarbamoyl, diethylcarbamoyl, ethylmethylcarbamoyl). Halogen atom means halogen atom such as fluorine atom, chlorine atom, bromine atom or iodine atom. Aryl refers to a C6-10monocyclic or fused cyclic aryl group, such as phenyl, indenyl, or naphthyl, and the like. Heterocyclic or heterocycle refers to monocyclic saturated heterocyclic groups, or unsaturated monocyclic or fused heterocyclic group containing at least one heteroatom, e.g., 0- 3 nitrogen atoms NRc, 0-1 oxygen atom (—O—), and 0-1 sulfur atom (—S—). Non-limiting 1133.122WO1, SD2025-069-2PCT examples of saturated monocyclic heterocyclic group includes 5 or 6 membered saturated heterocyclic group, such as tetrahydrofuranyl, pyrrolidinyl, morpholinyl, piperidyl, piperazinyl or pyrazolidinyl. Non-limiting examples of unsaturated monocyclic heterocyclic group includes 5 or 6 membered unsaturated heterocyclic group, such as furyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, thienyl, pyridyl or pyrimidinyl. Non-limiting examples of unsaturated fused heterocyclic groups includes unsaturated bicyclic heterocyclic group, such as indolyl, isoindolyl, quinolyl, benzothizolyl, chromanyl, benzofuranyl, and the like. A Het group can be a saturated heterocyclic group or an unsaturated heterocyclic group, such as a heteroaryl group. Substituents for substitution on the alkyl, aryl or heterocyclic groups described herein include, but are not limited to, hydroxy (OH), C1-6alkyl, hydroxyC1-6alkylene, C1-6alkoxy, C1-6alkoxyC1-6alkylene, C3-6cycloalkyl, amino (e.g., NH2, NHalkyl, and the like), cyano, halogen (e.g., Cl, Br, and F), or aryl. References in the specification to “one embodiment,” “an embodiment,” etc., indicate that the embodiment described may include a particular aspect, feature, structure, moiety, or characteristic, but not every embodiment necessarily includes that aspect, feature, structure, moiety, or characteristic. Moreover, such phrases may, but do not necessarily, refer to the same embodiment referred to in other portions of the specification. Further, when a particular aspect, feature, structure, moiety, or characteristic is described in connection with an embodiment, it is within the knowledge of one skilled in the art to affect or connect such aspect, feature, structure, moiety, or characteristic with other embodiments, whether or not explicitly described. As used herein, the term “in some embodiments” refers to embodiments of all aspects of the disclosure, unless the context clearly indicates otherwise. The singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to “a compound” includes a plurality of such compounds, so that a compound X includes a plurality of compounds X. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for the use of exclusive terminology, such as “solely,” “only,” and the like, in connection with any element described herein, and / or the recitation of claim elements or use of “negative” limitations. The term “and / or” means any one of the items, any combination of the items, or all of the items with which this term is associated. The phrase “one or more” is readily understood by one of skill in the art, particularly when read in context of its usage. For example, one or more substituents on a phenyl ring refers to one to five, or one to four, for example if the phenyl ring is di-substituted. 1133.122WO1, SD2025-069-2PCT As used herein, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating a listing of items, “and / or” or “or” shall be interpreted as being inclusive, e.g., the inclusion of at least one, but also including more than one of a number of items, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of” or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e., “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” As used herein, the terms “including,” “includes,” “having,” “has,” “with,” or variants thereof, are intended to be inclusive similar to the term “comprising.” The term “about” can refer to a variation of ± 5%, ± 10%, ± 20%, or ± 25% of the value specified. For example, “about 50” percent can in some embodiments carry a variation from 45 to 55 percent. For integer ranges, the term “about” can include one or two integers greater than and / or less than a recited integer at each end of the range. Unless indicated otherwise herein, the term “about” is intended to include values, e.g., weight percentages, proximate to the recited range that are equivalent in terms of the functionality of the individual ingredient, the composition, or the embodiment. The term about can also modify the endpoints of a recited range as discuss above in this paragraph. As will be understood by the skilled artisan, all numbers, including those expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth, are approximations and are understood as being optionally modified in all instances by the term “about.” These values can vary depending upon the desired properties sought to be obtained by those skilled in the art utilizing the teachings of the descriptions herein. It is also understood that such values inherently contain variability necessarily resulting from the standard deviations found in their respective testing measurements. As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges recited herein also encompass any and all possible sub-ranges and combinations of sub-ranges thereof, as well as the individual values making up the range, particularly integer values. A recited range (e.g., weight percentages or carbon groups) includes each specific value, integer, decimal, or identity within the range. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, or tenths. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle 1133.122WO1, SD2025-069-2PCT third and upper third, etc. As will also be understood by one skilled in the art, all language such as “up to,” “at least,” “greater than,” “less than,” “more than,” “or more,” and the like, include the number recited and such terms refer to ranges that can be subsequently broken down into sub-ranges as discussed above. In the same manner, all ratios recited herein also include all sub-ratios falling within the broader ratio. Accordingly, specific values recited for radicals, substituents, and ranges, are for illustration only; they do not exclude other defined values or other values within defined ranges for radicals and substituents. One skilled in the art will also readily recognize that where members are grouped together in a common manner, such as in a Markush group, the invention encompasses not only the entire group listed as a whole, but each member of the group individually and all possible subgroups of the main group. Additionally, for all purposes, the invention encompasses not only the main group, but also the main group absent one or more of the group members. The invention therefore envisages the explicit exclusion of any one or more of members of a recited group. Accordingly, provisos may apply to any of the disclosed categories or embodiments whereby any one or more of the recited elements, species, or embodiments, may be excluded from such categories or embodiments, for example, for use in an explicit negative limitation. The term “at least” prior to a number or series of numbers (e.g., “at least two”) is understood to include the number adjacent to the term “at least,” and all subsequent numbers or integers that could logically be included, as clear from context. When “at least” is present before a series of numbers or a range, it is understood that “at least” can modify each of the numbers in the series or range. As used herein, the terms “including”, “includes”, “having”, “has”, “with”, or variants thereof, are intended to be inclusive similar to the term “comprising.” The terms “comprises,” “comprising,” and the like can have the meaning ascribed to them in U.S. Patent Law and can mean “includes,” “including” and the like. As used herein, “including” or “includes” or the like means including, without limitation. In the methods described herein, the acts can be carried out in a specific order as recited herein. Alternatively, in any aspect(s) disclosed herein, specific acts may be carried out in any order without departing from the principles of the invention, except when a temporal or operational sequence is explicitly recited. Furthermore, specified acts can be carried out concurrently unless explicit claim language recites that they be carried out separately or the plain meaning of the claims would require it. For example, a claimed act of doing X and a 1133.122WO1, SD2025-069-2PCT claimed act of doing Y can be conducted simultaneously within a single operation, and the resulting process will fall within the literal scope of the claimed process. The term “contacting” refers to the act of touching, making contact, or of bringing to immediate or close proximity, including at the cellular or molecular level, for example, to bring about a physiological reaction, a chemical reaction, or a physical change, e.g., in a solution, in a reaction mixture, in vitro, or in vivo. As used herein, an “effective amount” or “therapeutically effective amount” refers to an amount of a compound, or an amount of a combination of compounds, to treat or prevent a disease or disorder or viral or microbial infection, or to treat or prevent a symptom of the disease or disorder or viral or microbial infection, in a subject. As used herein, the terms “subject” and “patient” generally refers to an individual who will receive or who has received treatment (e.g., administration of a compound) according to a method described herein. The term “elderly” or “advanced age” as used herein refers to a subject that is typically 65 years old or greater. Elderly may in include a subject that is at least 50 years old or at least 55 years old, or at least 60 years old. Elderly as used herein refers to any subject that is more prone to infection by an infectious agent and / or has a reduced capacity to prevent, control or alleviate an infection by an infectious agent due in whole or part to aging. The term “young child” as used herein refers to a subject that is typically under the age of 5 years. The term “delivery vehicle” or “carrier” refers to any kind of device or material which can be used to deliver the invention in vivo. As used herein, the term “pharmaceutically acceptable carrier” includes any of the standard pharmaceutical carriers, such as a phosphate buffered saline solution, water, emulsions such as an oil / water or water / oil emulsion, and various types of wetting agents. The term also encompasses any of the agents approved by a regulatory agency of the US Federal government or listed in the US Pharmacopeia for use in animals, including humans. When the active compound is mixed with a carrier, or when the carrier serves as a diluent, it can be solid, semi-solid, or liquid material that acts as a vehicle, excipient, or medium for the active compound. The active compound can be adsorbed on a granular solid carrier, for example contained in a sachet. Some examples of suitable carriers are water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, dextrin, magnesium carbonate, sugar, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid or lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, 1133.122WO1, SD2025-069-2PCT hydroxymethylcellulose and polyvinylpyrrolidone. Similarly, the carrier or diluent can include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. Pharmaceutically acceptable carriers (vehicles) useful in this disclosure can be conventional. Remington's Pharmaceutical Sciences, by E. W. Martin, Mack Publishing Co., Easton, PA, 15th Edition (1975), describes compositions and formulations suitable for pharmaceutical delivery of one or more therapeutic compositions, such as one or more therapeutic cancer vaccines, and additional pharmaceutical agents. The terms “treat” and “treating” as used herein refer to (i) preventing a pathologic condition from occurring (e.g., prophylaxis); (ii) inhibiting the pathologic condition or arresting its development; (iii) relieving the pathologic condition; and / or (iv) ameliorating, alleviating, lessening, and removing one or more symptoms of a condition. A candidate molecule or compound described herein may be in an amount in a formulation or medicament, which is an amount that can lead to a biological effect, or lead to protection from, ameliorating, alleviating, lessening, relieving, diminishing or a disease condition, e.g., infection, for example. These terms also are applicable to reducing a titer of a microorganism (microbe) or infectious agent in a system (e.g., cell, tissue, or subject) infected with a microbe, reducing the rate of microbial propagation, reducing the duration of infection of an infectious agent, delaying or attenuating an infection by an infectious agent, reducing the number of symptoms or an effect of a symptom associated with the microbial infection, and / or removing detectable amounts of the microbe from the system. Examples of symptoms include but are not limited weight loss, fever, malaise, weakness, dehydration, failure or diminished organ or organ system function (e.g., pulmonary function). Examples of microbes include but are not limited to viruses, bacteria and fungi. A “preventive” or “prophylactic” treatment is a treatment administered to a subject who does not exhibit signs, or exhibits only early signs, of a disease or disorder. A prophylactic or preventative treatment is administered for the purpose of decreasing the risk of developing pathology associated with developing the disease or disorder. As used herein, the term “therapeutic” means an agent utilized to treat, combat, ameliorate, prevent, or improve an unwanted condition or disease of a patient. The term “in need thereof' means that the subject has been identified or suspected as having a need for the particular method or treatment. In some embodiments, the identification can be by any means of diagnosis or observation. In any of the methods described herein, the subject can be in need thereof. 1133.122WO1, SD2025-069-2PCT As used herein “injecting, administering or applying” includes administration of the invention by any number of routes and means including, but not limited to, topical, oral, buccal, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual, ophthalmic, or pulmonary. As used herein, a “subject in need thereof” is a patient, animal (domestic (cat, dog) or farm animal (livestock, horse, cow), mammal, or human, who will benefit from the method of this invention. The terms “subject” refers to an animal, such as a mammalian species (e.g., human). More specifically, a subject can be a vertebrate, e.g., a mammal such as a mouse, a primate, a simian, or a human. Animals include farm animals (e.g., production cattle, dairy cattle, poultry, horses, pigs, and the like), sport animals, and companion animals (e.g., pets or support animals). A subject can be a healthy individual, an individual that has or is suspected of having a disease or a predisposition to the disease, or an individual that needs therapy or suspected of needing therapy. The terms “individual” or “patient” are intended to be interchangeable with “subject.” For example, a subject can be an individual who has been diagnosed with having a pathogenic infection, is going to receive a therapy for a pathogenic infection, has received at least one therapy for a pathogenic infection of prophylactic / preventative (e.g., vaccine) treatment. A disease, condition, or disorder is “alleviated” if the severity of a symptom of the disease or disorder, the frequency with which such a symptom is experienced by a subject, or both, are reduced. An immune response is a change in the activity of a cell of the immune system, such as a B cell, T cell, or monocyte, as a result of a stimulus, either directly or indirectly, such as through a cellular or cytokine intermediary. In one embodiment, the response is specific for a particular antigen (an “antigen-specific response”). In one embodiment, an immune response is a T cell response, such as a CD4 T cell response or a CD8 T cell response. In one embodiment, an immune response results in the production of additional T cell progeny. In one embodiment, an immune response results in the movement of T cells. In another embodiment, the response is a B cell response, and results in the production of specific antibodies or the production of additional B cell progeny. In other embodiments, the response is an antigen- presenting cell response. “Enhancing an immune response” refers to co-administration of an adjuvant and an immunogenic agent, such as a peptide antigen, as part of a peptide antigen conjugate, wherein the adjuvant increases the desired immune response to the immunogenic agent compared to administration of the immunogenic agent to the subject in the absence of 1133.122WO1, SD2025-069-2PCT the adjuvant. In some embodiments, an antigen is used to stimulate an immune response leading to the activation of cytotoxic T cells that kills virally infected cells or cancerous cells. In some embodiments, an antigen is used to induce tolerance or immune suppression. A tolerogenic response may result from the unresponsiveness of a T cell or B cell to an antigen. A suppressive immune response may result from the activation of regulatory cells, such as regulatory T cells that downregulate the immune response, i.e. dampen then immune, response. Antigens administered to a patient in the absence of an adjuvant are generally tolerogenic or suppressive and antigens administered with an adjuvant are generally stimulatory and lead to the recruitment, expansion and activation of immune cells. Immunogenic composition comprises a formulation of materials comprising an antigen and an adjuvant that induces a measurable immune response against the antigen. An adjuvant is a substance added to vaccines to enhance and strengthen the immune response to the vaccine antigen. It helps the body produce a stronger and often longer-lasting immunity against the targeted disease by activating the innate immune system and promoting signals that stimulate adaptive immunity. A co-adjuvant, on the other hand, is used in combination with a primary adjuvant to further improve or modulate the immune response. The co-adjuvant may aid in delivering the antigen and primary adjuvant to immune cells more effectively or enhance the activation of specific immune pathways. Co-adjuvants can act synergistically with the main adjuvant to optimize the vaccine's efficacy, sometimes enabling the use of lower doses of each component to minimize side effects while maximizing protective immunity. The core difference is that an adjuvant is the main immune-stimulating component in the vaccine, whereas a co-adjuvant is an additional substance used alongside the primary adjuvant to augment or complement its effect. Generally, the difference between self-assembling nanoparticles and lipid-incorporated nanoparticles lies in their composition and the mechanism of their formation. Self-assembling nanoparticles are formed through the process of nanoprecipitation or self-assembly, where lipid molecules or other components spontaneously organize under specific conditions, such as controlled mixing of lipid and aqueous phases. This process leads to the formation of nanoparticle seeds which grow and stabilize into particles. These nanoparticles often consist mainly of lipids that arrange themselves around a payload (such as drugs or nucleic acids) and form stable colloidal particles by themselves through electrostatic interactions and hydrophobic forces. Lipid-incorporated nanoparticles (often called lipid nanoparticles or LNPs), on the other hand, are a specific type of self-assembling nanoparticle that include lipids such as phospholipids, cholesterol, PEGylated lipids, and ionizable or cationic lipids. LNPs are 1133.122WO1, SD2025-069-2PCT predominantly used as drug delivery vehicles, especially for RNA-based therapeutics like mRNA vaccines. They have a more complex lipid composition forming multilayer or bilayer structures that encapsulate the payload and protect it for delivery to target cells. LNPs rely on careful lipid formulation to optimize stability, encapsulation efficiency, and cellular uptake. Thus, self-assembling nanoparticles refer broadly to particles formed by spontaneous organization of molecules, which can include lipid particles, while lipid-incorporated nanoparticles specifically refer to those nanoparticles formed and stabilized by lipid components tailored for drug or gene delivery purposes. Generally, lipid-incorporated nanoparticles (lipid nanoparticles, or LNPs) differ from aqueous or liposomal combinations primarily in their structure, composition, and morphology. Lipid-incorporated nanoparticles (LNPs) have a solid or multilayer lipid core that encapsulates substances like nucleic acids. They typically contain ionizable cationic lipids, cholesterol, PEGylated lipids, and structural lipids. LNPs do not have an aqueous internal cavity; instead, the cargo is embedded and stabilized within the lipid matrix, making them more compact and stable. LNPs are widely used for delivering genetic material such as mRNA. Liposomes are spherical vesicles composed of one or more phospholipid bilayers surrounding an aqueous core. They enclose hydrophilic substances inside the aqueous cavity and lipophilic substances within the lipid bilayer. Liposomes have a more open bilayer vesicle structure with an aqueous internal cavity, which makes them versatile for encapsulating various drug types but relatively less stable than LNPs. Aqueous or liposomal combinations refer generally to formulations where liposomes are suspended in an aqueous medium, forming vesicles with water-filled cores surrounded by lipid bilayers. Thus, LNPs have a solid or complex lipid core without an aqueous cavity and are formulated mainly for nucleic acid delivery with high stability, whereas liposomes are bilayer vesicles with aqueous cavities used for encapsulating both hydrophilic and lipophilic drugs but tend to be less structurally rigid. Co-encapsulated combinations and admixed combinations in nanoparticles differ in how the components (such as drugs or antigens and adjuvants) are formulated and delivered. Co-encapsulated combinations refer to two or more components being encapsulated together inside the same nanoparticle carrier. This approach enables synchronized delivery of both components directly to the target site. Co-encapsulation can provide synergistic effects because both components reach the cells simultaneously, potentially improving therapeutic efficacy and minimizing systemic side effects. Achieving successful co-encapsulation requires matched diffusion and assembly characteristics of the components to ensure they are incorporated proportionally into the same particle. Admixed combinations involve separately preparing 1133.122WO1, SD2025-069-2PCT nanoparticles with different components and then mixing these distinct nanoparticle populations together before administration. The components are not physically combined inside the same particle but are delivered together as a mixture of different particles. This can be easier to achieve but may result in less coordinated delivery and interaction at the cellular level. In immunological applications, such as synthetic vaccine particles, co-encapsulation of antigen and adjuvant in one particle can enhance immune responses and reduce systemic inflammation compared to admixed particles where antigen and adjuvant are delivered separately but concurrently. Thus, co-encapsulated combinations are single nanoparticles with multiple payloads inside, while admixed combinations are mixtures of distinct nanoparticles each carrying different payloads. A nanoparticle, as used herein, refers to a particle having at least one dimension in the nanometer range, typically from about 1 nanometer (nm) to about 1000 nm. Nanoparticles may be composed of lipids, polymers, proteins, or other materials, and are capable of encapsulating, adsorbing, or otherwise associating with active agents such as adjuvants or antigens. In the context of vaccine formulations, nanoparticles are used to enhance delivery, stability, and immunogenicity of the associated agents. A micelle, as used herein, refers to an aggregate of amphiphilic molecules (such as surfactants or lipids) that spontaneously arrange themselves in an aqueous environment to form a colloidal particle with a hydrophobic core and a hydrophilic shell. Micelles typically have a diameter in the range of about 5 nm to about 100 nm. They are capable of solubilizing hydrophobic compounds within their core and are used as delivery vehicles in pharmaceutical formulations. An emulsion, as used herein, refers to a colloidal system comprising two immiscible liquids, where one liquid (the dispersed phase) is distributed in the form of small droplets throughout the other liquid (the continuous phase). Emulsions may be oil-in-water (O / W), water-in-oil (W / O), or more complex types, and are stabilized by surfactants or emulsifying agents. In vaccine technology, emulsions are often used as adjuvant systems to enhance immune responses. An aqueous formulation, as used herein, refers to a pharmaceutical or vaccine composition in which the primary solvent or continuous phase is water or an aqueous buffer. Aqueous formulations may contain dissolved, suspended, or dispersed active agents, including nanoparticles, micelles, or emulsions, and may include additional excipients such as stabilizers, preservatives, or tonicity agents. Aqueous formulations are suitable for parenteral, mucosal, or other routes of administration. 1133.122WO1, SD2025-069-2PCT In a vaccine context, “boost” or “booster” refers to an additional dose of a vaccine given after the initial (primary) series of vaccination. The purpose of a booster dose is to re-expose the immune system to the immunizing antigen and enhance or restore immunity that may have decreased over time since the primary vaccination. Boosters help maintain or increase protection by stimulating the immune system to “remember” the pathogen and produce a stronger immune response, often improving the quantity and quality of antibodies and memory cells. They are commonly used for diseases where immunity wanes with time, such as tetanus, COVID-19, and pertussis. Thus, a booster dose “boosts” the immune memory and prolongs vaccine effectiveness against infection or disease. Dose-sparing effects refer to strategies and approaches that reduce the amount of vaccine antigen needed per dose while still achieving effective immune protection. These approaches help stretch limited vaccine supplies, increase availability during shortages or pandemics, and may involve using fractional doses, adjuvants, alternative delivery methods, or modified dosing intervals. Dose-sparing strategies in vaccines include, but are not limited to, fractional dosing (administering a lower-than-standard amount of antigen (such as one-fifth or one-half dose) while still eliciting a protective immune response. For example, fractional dosing with certain polio and influenza vaccines has shown comparable antibody production to full-dose regimens); use of adjuvants (adding immune-boosting agents (such as alum or squalene-based emulsions) that enhance the immune response, allowing for lower antigen amounts to confer similar protection); alternative delivery methods (techniques like intradermal (skin) administration or microneedle patches can be more immunologically efficient, achieving dose-sparing effects compared to intramuscular injection), and dose interval adjustments (lengthening the time between vaccine doses can sometimes lead to stronger immune responses with less antigen, as seen in some COVID-19 vaccine trials). Being immunocompromised means a person's immune system is weakened or not functioning properly, making it less capable of fighting off infections and diseases. This weakened immune state can be temporary or permanent and may result from health conditions (like cancer, diabetes, HIV), medical treatments (such as chemotherapy, immunosuppressive drugs, organ transplants), genetic disorders, or aging. People who are immunocompromised are more susceptible to infections and are at higher risk for more severe illnesses compared to those with a healthy immune system. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this technology belongs. Although exemplary methods, devices and materials are described herein, any 1133.122WO1, SD2025-069-2PCT methods and materials similar or equivalent to those expressly described herein can be used in the practice or testing of the present technology. For example, the reagents described herein are merely exemplary and that equivalents of such are known in the art. Compounds Relating to the Present Disclosure In one embodiment, the adjuvant and co-adjuvants have the following structures: wherein X1is -O-, -S-, or -NRc-; R1is hydrogen, (C1-C10)alkyl, substituted (C1-C10)alkyl, C6-10aryl, or substituted C6-10aryl, C5-9heterocyclic, or substituted C5-9heterocyclic; Rcis hydrogen, C1-10alkyl, or substituted C1-10alkyl; or Rcand R1taken together with the nitrogen to which they are attached form a heterocyclic ring or a substituted heterocyclic ring; each R2is independently -OH, (C1-C6)alkyl, substituted (C1-C6)alkyl, (C1-C6)alkoxy, substituted (C1-C6)alkoxy, -C(O)-(C1-C6)alkyl (alkanoyl), substituted -C(O)-(C1-C6)alkyl, - C(O)-(C6-C10)aryl (aroyl), substituted -C(O)-(C6-C10)aryl, -C(O)OH (carboxyl), -C(O)O(C1-C6)alkyl (alkoxycarbonyl), substituted -C(O)O(C1-C6)alkyl, -NRaRb, -C(O)NRaRb(carbamoyl), halo, nitro, or cyano, or R2is absent; each Raand Rbis independently hydrogen, (C1-C6)alkyl, substituted (C1-C6)alkyl, (C3- C8)cycloalkyl, substituted (C3-C8)cycloalkyl, (C1-C6)alkoxy, substituted (C1-C6)alkoxy, (C1- C6)alkanoyl, substituted (C1-C6)alkanoyl, aryl, aryl(C1-C6)alkyl, Het, Het (C1-C6)alkyl, or (C1-C6)alkoxycarbonyl; wherein the substituents on any alkyl, aryl or heterocyclic groups are hydroxy, C1-6alkyl, hydroxyC1-6alkylene, C1-6alkoxy, C3-6cycloalkyl, C1-6alkoxyC1-6alkylene, amino, cyano, halo, or aryl; n is 0, 1, 2, 3 or 4; X2is a bond or a linking group; and R3is a phospholipid or analog thereof comprising one or two alkyl ethers or carboxylic esters of the glyceryl moiety; or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof. 1133.122WO1, SD2025-069-2PCT wherein the composition further comprises a co-adjuvant and / or an antigen. In one embodiment, R3comprises a group of formula: wherein: R11and R12are each independently a C8-C25acyl group; R13is a negative charge or a hydrogen, and R14is a C1-C8n-alkyl or branched alkyl group which can be substituted or unsubstituted, wherein optionally one of the carbon atoms of the alkyl group is replaced by NH, S, or O; Z is O, S, or NH, and q is 0 or 1; the wavy line indicates a position of bonding, wherein an absolute configuration at the carbon atom bearing OR12is R, S, or any mixture thereof. In another embodiment, Z is O and q is 1. In another embodiment, R14is a C1alkyl group or a C2alkyl group. In still another embodiment, X2is -C(O)-. In yet another embodiment, X1is O. In embodiments, each R3is a C8-C25acyl group comprising one, two, three or four sites of unsaturation, epoxidation, hydroxylation, or a combination thereof. In one example, each C8-C25acyl group comprises one site of unsaturation. Thus, for example, each C8-C25acyl group can be of the formula: . In one embodiment, R1is (C1-C10)alkyl. And in another embodiment, R2is absent. In one example, the compound of the Formula (I) is 1V270, a TLR7 Agonist, is an oxoadenine pharmacophore conjugated to DOPE (Chan, 2009; Chan, 2011; Hayashi, 2011), which showed excellent vaccine adjuvant efficacy as a single agent and in combination with TLR4 ligands (Sato-Kaneko, 2022; Sato-Kaneko, 2022; Goff, 2017; Goff, 2015). Chemical Formula: C57H92N6O12P-. Molecular Weight: 1084.37 1133.122WO1, SD2025-069-2PCT . The compounds of the disclosure also include compounds of Formula (II), (III), and (IV): (Formula (II)), or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R15is selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R16and R17are each independently selected from -Br, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; and R18is selected from substituted or unsubstituted aryl (e.g., benzyl and naphthyl), or substituted or unsubstituted heteroaryl (e.g., benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]selenadiazolyl, and quinolinyl); 1133.122WO1, SD2025-069-2PCT (Formula (III)) or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R19is hydrogen, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R20is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; and R21is -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or (Formula (IV)) or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R22is hydrogen, halogen, -CN, -SH, -OH, -COOH, -NH2, -CONH2, nitro, -CF3, -CCl3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; R23is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R24is substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl; and 1133.122WO1, SD2025-069-2PCT R25is halogen, -CN, -SH, -OH, -COOH, -NH2, -CONH2, -NO2, -CF3, -CCl3, -PO4, substituted and unsubstituted phosphates, -SO4, substituted and unsubstituted alkyls, substituted and unsubstituted alkenes, substituted and unsubstituted alkynes, azides, esters, amides, ethers including substituted and unsubstituted alkyls, lipids, phospholipids, PEGs, linkers not limited to substituted carbonates, substituted carbamates and oxalate, succinate. The compounds of the disclosure also include compounds of Formula (V), (VI) or (VII): (Formula (V)) or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R26and R27are each independently selected from -Br, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; R28is selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and G is S or Se; (Formula (VI)) or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: 1133.122WO1, SD2025-069-2PCT R29is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R30is H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, -NH2or -OH; or or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R31is hydrogen, halogen, -CN, -SH, -OH, -COOH, -NH2, -CONH2, nitro (NO2), -CF3, -CCl3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; and R32is H; OR32A, wherein R32Ais H, substituted or unsubstituted alkyl, substituted or unsubstituted alkynyl or substituted or unsubstituted alkenyl; or NHR32B, wherein R32Bis H or acyl. The compounds of the disclosure also include: 1133.122WO1, SD2025-069-2PCT 2G272, a Calcium Influx Inducer. Chemical Formula: C15H15N3O4S2Se. Molecular Weight: 444.39; and 2E151 a Calcium Channel Activator. Chemical Formula: C26H31N3O3S2. Molecular Weight 497.67. In one embodiment, the compositions described herein are useful as a vaccine adjuvant. In one embodiment, the compositions may be in a pharmaceutical composition comprising a pharmaceutically acceptable carrier. In one embodiment, a method of enhancing or prolonging an immune response in a mammal is provided, comprising: administering to a mammal in need thereof a vaccine or an immunogenic / antigenic moiety (e.g., any antigen, such as a protein or carbohydrate component of virus or bacteria) and an effective amount of the compositions described herein. In one embodiment, the vaccine / immunogenic / antigenic moiety and composition described herein are co-administered. In one embodiment, the vaccine / immunogenic / antigenic moiety and composition described herein are sequentially administered. In one embodiment, the mammal is a human. In some embodiments, the composition comprises nanoparticles. As used herein, a nanoparticle has a diameter of about 30 nm to about 600 nm, or a range with any integer 1133.122WO1, SD2025-069-2PCT between 30 and 600, e.g., about 40 nm to about 250 nm, including about 40 to about 80 or about 100 nm to about 150 nm in diameter. The nanoparticles may be formed by mixing a compound provided herein which may spontaneously form nanoparticles, or by mixing a compound provided herein with a preparation of lipids, such as phospholipids including but not limited to phosphatidylcholine, phosphatidylserine or cholesterol, thereby forming a nanoliposome. In certain embodiments, a composition forms particles of about 10 nanometers to about 1000 nanometers, and sometimes, a composition forms particles with a mean, average or nominal size of about 100 nanometers to about 400 nanometers. Lipids are fatty acid derivatives with various head group moieties. Triglycerides are lipids made from three fatty acids and a glycerol molecule (a three-carbon alcohol with a hydroxyl group (OH) on each carbon atom). Mono- and diglycerides are glyceryl mono- and di-esters of fatty acids. Phospholipids are similar to triglycerides except that the first hydroxyl of the glycerol molecule has a polar phosphate-containing group in place of the fatty acid. Phospholipids are amphiphilic, possessing both hydrophilic (water soluble) and hydrophobic (lipid soluble) groups. The head group of a phospholipid is hydrophilic and its fatty acid tail (acyl chain) is hydrophobic. The phosphate moiety of the head group is negatively charged. In addition to lipid and / or phospholipid molecules, nanoliposomes may contain other molecules such as sterols in their structure. Sterols are important components of most natural membranes, and incorporation of sterols into nanoliposome bilayers can bring about major changes in the properties of these vesicles. The most widely used sterol in the manufacture of the lipid vesicles is cholesterol (Chol). Cholesterol does not by itself form bilayer structures, but it can be incorporated into phospholipid membranes in very high concentrations, for example up to 1:1 or even 2:1 molar ratios of cholesterol to a phospholipid such as phosphatidylcholine (PC) (11). Cholesterol is used in nanoliposome structures in order to increase the stability of the vesicles by modulating the fluidity of the lipid bilayer. In general, cholesterol modulates fluidity of phospholipid membranes by preventing crystallization of the acyl chains of phospholipids and providing steric hindrance to their movement. This contributes to the stability of nanoliposomes and reduces the permeability of the lipid membrane to solutes. Physicochemical properties of nanoliposomes depend on several factors including pH, ionic strength and temperature. Generally, lipid vesicles show low permeability to the entrapped material. However, at elevated temperatures, they undergo a phase transition that alters their permeability. Phospholipid ingredients of nanoliposomes have an important thermal characteristic, i.e., they can undergo a phase transition (Tc) at temperatures lower than their 1133.122WO1, SD2025-069-2PCT final melting point (Tm). Also known as gel to liquid crystalline transition temperature, Tc is a temperature at which the lipidic bilayer loses much of its ordered packing while its fluidity increases. Phase transition temperature of phospholipid compounds and lipid bilayers depends on the following parameters: polar head group; acyl chain length; degree of saturation of the hydrocarbon chains; and nature and ionic strength of the suspension medium. In general, Tc is lowered by decreased chain length, by unsaturation of the acyl chains, as well as presence of branched chains and bulky head groups (e.g. cyclopropane rings). Hydrated phospholipid molecules arrange themselves in the form of bilayer structures via Van-der Waals and hydrophilic / hydrophobic interactions. In this process, the hydrophilic head groups of the phospholipid molecules face the water phase while the hydrophobic region of each of the monolayers face each other in the middle of the membrane. It should be noted that formation of liposomes and nanoliposomes is not a spontaneous process and sufficient energy must be put into the system to overcome an energy barrier. In other words, lipid vesicles are formed when phospholipids such as lecithin are placed in water and consequently form bilayer structures, once adequate amount of energy is supplied. Input of energy (e.g. in the form of sonication, homogenization, heating, etc.) results in the arrangement of the lipid molecules, in the form of bilayer vesicles, to achieve a thermodynamic equilibrium in the aqueous phase. Antigens / Immune Moieties An antigen, in the context of a vaccine or an immunogenic composition, is any substance-typically a component of a pathogen or a product it produces-that stimulates the immune system to recognize it as foreign and generate a targeted immune response, including the creation of antibodies or activation of immune cells. Antigens used in vaccines may include parts of viruses, bacteria, or toxins, such as whole or weakened (attenuated) viruses or bacteria, inactivated viruses or bacteria, specific proteins or polysaccharides (carbohydrates) present on the pathogen’s surface, bacterial toxins which have been chemically inactivated (“toxoids”) and / or mRNA coding for a viral protein (as found in some COVID-19 vaccines). The immune system responds to the introduced antigen without causing disease, “training” the body to recognize and respond more rapidly if exposed to the actual pathogen later. Examples of vaccine antigens include, but are not limited to, influenza vaccine (contains hemagglutinin and neuraminidase proteins from the influenza virus), hepatitis B vaccine (uses the hepatitis B surface antigen (HBsAg), a recombinant protein), diphtheria and tetanus vaccines: (use toxoids—chemically inactivated bacterial toxins), pneumococcal vaccine (contains polysaccharide antigens from the Streptococcus pneumoniae bacterium’s 1133.122WO1, SD2025-069-2PCT capsule) and COVID-19 mRNA vaccines (encode the SARS-CoV-2 spike protein, producing the antigen within cells for immune recognition). These examples illustrate how vaccine antigens are derived from parts of the pathogen to trigger protective immunity safely and effectively. In some embodiments, the viral or bacterial protein or carbohydrate is from Dengue, West Nile Virus, Zika fever, Coronavirus disease 2019, Nipah virus infection, Lyme disease, Malaria, Marburg virus, Rift Valley fever, Tuberculosis, Avian flu, Chikungunya, Cholera, Ebola, E. coli, Hantavirus Infection, HIV Infections, Pertussis, Pneumococcal disease, SARS- CoV and SARS-CoV-2, Crimean–Congo hemorrhagic fever, Gonorrhea, Influenza, Middle East respiratory syndrome, MRSA, RSV, Varicella-zoster virus, H. pylori infections, Human papilloma, Hepatitis A, B, and C, Epstein Barr virus, HSV 1,2,6, Anthrax, Smallpox, or Tularemia protein or carbohydrate, such as a viral protein, e.g., spike or capsid protein. In some embodiments the antigen is an inactivated / dead or attenuated virus, such as a Dengue, West Nile Virus, Zika fever, Coronavirus disease 2019, Nipah virus infection, Marburg virus, Rift Valley fever, Avian flu, Chikungunya, Ebola, Hantavirus Infection, HIV Infections, SARS- CoV and SARS-CoV-2, Crimean–Congo hemorrhagic fever, Influenza, Middle East respiratory syndrome, RSV, Varicella-zoster virus, Human papilloma, Hepatitis A, B, and C, Epstein Barr virus, HSV 1,2,6, Smallpox virus or combination thereof. Immunogenic compositions may comprise one or more different antigens, such as peptide antigens, carbohydrate antigens and / or nucleic acid antigens. The length of the peptide antigen (A) depends on the specific application and is typically between about 5 to about 50 amino acids. In preferred embodiments, the peptide antigen (A) is between about 7 to 35 amino acids, e.g., 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 or 35 amino acids, or a full length protein. Antigens use in embodiments of the present disclosure may be selected from pathogens, cancerous cells, auto-antigens or allergens. In some embodiments, the antigen can be a peptide- based antigen that can include a region of a polypeptide or protein from a pathogen (such as a virus, bacteria, or fungi) or a tissue of interest (such as a cancerous cell). In other embodiments, the antigen can be a whole protein or glycoprotein derived from a pathogen, or a peptide or glycopeptide fragment of the protein or glycoprotein. In other embodiments, the antigen can be a protein, or peptide fragments of a protein, that is expressed primarily by tumor tissue (but not healthy tissue) and is a tumor-associated antigen. In other embodiments, the antigen is protein or peptide that is associated with auto-immunity. In still other embodiments, the antigen 1133.122WO1, SD2025-069-2PCT is a protein or glycoprotein that is associated with allergies. In other embodiments, the antigen is a carbohydarate. In some embodiments, the antigen is a cancer antigen, such as those found in the cancer vaccines. Examples of cancer vaccines include, but are not limited to, protein or peptide-based vaccines (those which use specific proteins or peptide fragments from cancer cells to stimulate immunity, e.g., HER2 peptides (NeuVax) for breast cancer, HPV16 E7 peptides for cervical cancer); nucleic acid-based vaccines (DNA or RNA) (provide genetic instructions for cells to produce tumor antigens, inducing immune response, e.g., mRNA-4157 / V940 (personalized mRNA vaccines in clinical trials for various cancers, including skin and pancreatic cancers)); cell-based vaccines (use whole tumor cells or dendritic cells loaded with tumor antigens, e.g., Sipuleucel-T (Provenge) for metastatic prostate cancer; autologous dendritic cell vaccines); viral vector vaccines (use genetically modified viruses to deliver cancer antigens and stimulate immune responses, e.g., T-VEC (Imlygic), an oncolytic virus vaccine for advanced melanoma; Bacillus Calmette-Guérin (BCG), a bacterial vaccine used to treat bladder cancer); investigational and personalized platforms (personalized mRNA vaccines tailored to patient's tumor mutations; DNA vaccines under trial for cancers like breast, cervical (HPV-related), melanoma). These vaccines work by stimulating the immune system to recognize and attack cancer cells, offering new options for cancer treatment beyond traditional therapies. Antigens that can be expressed by tumor cells include, but are not limited to, CLPP, Cyclin-A1, MAGE- A1, MAGE-C1, MAGE-C2, SSX2, XAgE1b / GAGED2a, Melan-A / MART-1, TRP-1, Tyrosinase, CD45, glypican-3, IGF2B3, Kallikrein 4, KIF20A, Lengsin, Meloe, MUC5AC, surviving, prostatic acid phosphatase, NY-ESO-1 and MAGE-A3. Routes of Administration / Method of Inducing an Immune Response The compositions described herein can be used to elicit an immune response tin a subject. Subjects that can benefit from the disclosed methods include human and veterinary subjects. In some embodiments, a subject is selected for treatment that has, or is at risk for developing, an infection with an infectious agent that comprises the antigen, for example because of exposure or the possibility of exposure to the infectious agent. Following administration of a therapeutically effective amount of a disclosed immunogenic composition, the subject can be monitored for the infection, symptoms associated with the infection, or both. In some embodiments, a subject is selected for treatment that has, or is at risk for developing, a cancer, such as a malignant tumor. Following administration of an effective 1133.122WO1, SD2025-069-2PCT amount of a disclosed immunogen, the subject can be monitored for the presence of the cancer, a reduction in tumor burden, any appropriate symptom of the cancer, or a combination thereof. The administration of a therapeutically effective amount of an immunogenic composition including a peptide antigen as disclosed herein can be for prophylactic or therapeutic purposes. When provided prophylactically, the immunogenic composition is provided in advance of any symptom, for example in advance of infection or development of a tumor. The prophylactic administration of the immunogenic composition serves to prevent or ameliorate subsequent development of the disease or condition. Hence in some embodiments the methods involve selecting a subject at risk for contracting an infection or developing a tumor, and administering a therapeutically effective amount of a disclosed therapeutically effective amount of a disclosed immunogenic composition. The immunogenic composition can thus be provided prior to the anticipated exposure to the infectious agent, or development of the tumor, so as to attenuate the anticipated severity, duration or extent of an infection or tumor, and / or any associated disease symptoms. When provided therapeutically, the disclosed immunogenic composition can be provided at or after the onset of a symptom of disease or condition, for example after development of a symptom of infection, or diagnosis of infection, or development of a symptom of a tumor, or diagnosis of a tumor. Treatment of the infection or tumor can include delaying and / or reducing signs or symptoms of the infection or tumor in the subject. In some examples, treatment using the methods disclosed herein prolongs the time of survival of the subject. The immunogenic composition can be used in coordinate immunization protocols or combinatorial formulations. In some embodiments, a therapeutically effective amount of a disclosed immunogenic composition can be administered to a subject to treat or inhibit an infectious agent in a subject. An infectious agent is an agent that can infect a subject, including, but not limited to, viruses, bacteria, and fungi. The subject can be selected for treatment that has, is suspected of having or is at risk of developing an infection with the infectious agent. In some embodiments, the infectious agent is a virus, a bacteria, or a fungus as described above, and the peptide antigen includes an antigen from the particular virus, bacteria, or fungus. The effective amount will depend upon the severity of the disease and the general state of the patient's health. A therapeutically effective amount is that which provides either subjective relief of a symptom(s) or an objectively identifiable improvement as noted by the clinician or other qualified observer. In one embodiment, a therapeutically effective amount is 1133.122WO1, SD2025-069-2PCT the amount necessary to inhibit tumor growth, or the amount that is effective at reducing a sign or a symptom of the tumor. In another embodiment, a therapeutically effective amount is the amount necessary to inhibit infection by an infectious agent, or the amount that is effective at reducing a sign or a symptom of the infection. The therapeutically effective amount of the agents administered can vary depending upon the desired effects and the subject to be treated. In some examples, therapeutic amounts are amounts which eliminate or reduce the patient's tumor burden, or which prevent or reduce the proliferation of metastatic cells, or which reduce the load of infectious agent in the subject. The actual dosage of the immunogenic composition will vary according to factors such as the disease indication and particular status of the subject (for example, the subject's age, size, fitness, extent of symptoms, susceptibility factors, and the like), time and route of administration, other drugs or treatments being administered concurrently, as well as the specific pharmacology of the compound for eliciting the desired activity or biological response in the subject. Dosage regimens can be adjusted to provide an optimum prophylactic or therapeutic response. A therapeutically effective amount is also one in which any toxic or detrimental side effects of the compound and / or other biologically active agent is outweighed in clinical terms by therapeutically beneficial effects. Dosage can be varied by the attending clinician to maintain a desired concentration at a target site (for example, the lungs or systemic circulation). Higher or lower concentrations can be selected based on the mode of delivery, for example, trans-epidermal, rectal, oral, pulmonary, intraosseous, or intranasal delivery versus intravenous or subcutaneous or intramuscular delivery. Dosage can also be adjusted based on the release rate of the administered formulation, for example, of an intrapulmonary spray versus powder, sustained release oral versus injected particulate or transdermal delivery formulations, and so forth. Any method of administration can be used for the disclosed therapeutic agents, including local and systemic administration. For example, topical, oral, intravascular such as intravenous, intramuscular, intraperitoneal, intranasal, intradermal, intrathecal and subcutaneous administration can be used. The particular mode of administration and the dosage regimen will be selected by the attending clinician, taking into account the particulars of the case (for example the subject, the disease, the disease state involved, and whether the treatment is prophylactic). In cases in which more than one agent or composition is being administered, one or more routes of administration may be used. One non-limiting example of a route of administration of a compound / composition is to the respiratory system. The respiratory system includes the nasal cavity and associated 1133.122WO1, SD2025-069-2PCT sinuses, the nasopharynx, oropharynx, larynx, trachea, bronchi, bronchioles, respiratory bronchioles, alveolar ducts and alveolar sacs. In specific embodiments the compounds described herein are administered to the lungs or the nasal cavity. Pulmonary administration can be used for delivery to the lungs and other regions of the respiratory system. Pulmonary administration includes, but is not limited to, aerosol inhalation via nasal (intranasal) or oral routes and intratracheal instillation. Aerosol inhalation is by any means by which an aerosol can be introduced into the respiratory system, including, but not limited to, pressurized metered dose inhalers, dry power inhalers and nebulizers (e.g., liquid spray and suspension spray) for oral route or any device suitable for intranasal administration. In addition, in some embodiments, are provided various dosage formulations for inhalation delivery. For example, formulations may be designed for aerosol use in devices such as metered-dose inhalers, dry powder inhalers and nebulizers. Intratracheal instillation can be carried out by delivering a solution into the lungs via a device, such as a syringe. Intranasal administration which can be employed to effect pulmonary administration can be used specifically for administration to the nasal cavity and sinuses. Devises for intranasal administration include, but are not limited to liquid drop devices, spray devices, dry powder devices and aerosol devices. Intranasal administration can also be by nasal gel or insuffulations. Formulation of the compounds described herein as aerosols (solid or liquid particles), liquids, powders, gels, nanoparticles may be obtained using standard procedures well known in the art. The compositions may also be administered parenterally, for example, intravenously, intra-arterially, intraperitoneally, intrathecally, intraventricularly, intraurethrally, intrasternally, intracranially, intramuscularly, or subcutaneously. Such administration may be as a single bolus injection, multiple injections, or as a short- or long-duration infusion. Implantable devices (e.g., implantable infusion pumps) may also be employed for the periodic parenteral delivery over time of equivalent or varying dosages of the particular formulation. For such parenteral administration, the compounds may be formulated as a sterile solution in water or another suitable solvent or mixture of solvents. The solution may contain other substances such as salts, sugars (particularly glucose or mannitol), to make the solution isotonic with blood, buffering agents such as acetic, citric, and / or phosphoric acids and their sodium salts, and preservatives. 1133.122WO1, SD2025-069-2PCT The compositions can be formulated as pharmaceutical compositions and administered to a mammalian host, such as a human patient in a variety of forms adapted to the chosen route of administration, e.g., by pulmonary routes, orally or parenterally, by intravenous, intramuscular, topical or subcutaneous routes. Thus, the present compositions may be systemically administered, e.g., orally, in combination with a pharmaceutically acceptable vehicle such as an inert diluent or an assimilable edible carrier. They may be enclosed in hard- or soft-shell gelatin capsules, may be compressed into tablets, or may be incorporated directly with the food of the patient's diet. For oral therapeutic administration, the compositions may be combined with one or more excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. Such compositions and preparations should contain at least 0.1% of active compound. The percentage of the compositions and preparations may, of course, be varied and may conveniently be between about 2 to about 60% of the weight of a given unit dosage form. The amount of adjuvants in such useful compositions is such that an effective dosage level will be obtained. The tablets, troches, pills, capsules, and the like may also contain the following: binders such as gum tragacanth, acacia, corn starch or gelatin; excipients such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid and the like; a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, fructose, lactose or aspartame or a flavoring agent such as peppermint, oil of wintergreen, or cherry flavoring may be added. When the unit dosage form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier, such as a vegetable oil or a polyethylene glycol. Various other materials may be present as coatings or to otherwise modify the physical form of the solid unit dosage form. For instance, tablets, pills, or capsules may be coated with gelatin, wax, shellac or sugar and the like. A syrup or elixir may contain the active compound, sucrose or fructose as a sweetening agent, methyl and propylparabens as preservatives, a dye and flavoring such as cherry or orange flavor. Of course, any material used in preparing any unit dosage form should be pharmaceutically acceptable and substantially non-toxic in the amounts employed. In addition, the adjuvants or other agents may be incorporated into sustained-release preparations and devices. The compositions may also be administered intravenously or intraperitoneally by infusion or injection. Solutions of the compositions can be prepared in water, optionally mixed with a nontoxic surfactant. Dispersions can also be prepared in glycerol, liquid polyethylene 1133.122WO1, SD2025-069-2PCT glycols, triacetin, 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 dosage forms suitable for injection or infusion can include sterile aqueous solutions or dispersions or sterile powders comprising the active ingredient which are adapted for the extemporaneous preparation of sterile injectable or infusible solutions or dispersions, optionally encapsulated in liposomes. In all cases, the ultimate dosage form should be sterile, fluid and stable under the conditions of manufacture and storage. The liquid carrier or vehicle can be a solvent or liquid dispersion medium comprising, for example, water, ethanol, a polyol (for example, glycerol, propylene glycol, liquid polyethylene glycols, and the like), vegetable oils, nontoxic glyceryl esters, and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the formation of liposomes, by the maintenance of the required particle size in the case of dispersions or by the use of surfactants. The prevention of the action of microorganisms during storage can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it may be useful to include isotonic agents, for example, sugars, buffers 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 compound(s) in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filter sterilization. In the case of sterile powders for the preparation of sterile injectable solutions, one method of preparation includes vacuum drying and the freeze- drying techniques, which yield a powder of the active ingredient plus any additional desired ingredient present in the previously sterile-filtered solutions. For topical administration, the compounds may be applied in pure form, e.g., when they are liquids. However, it will generally be desirable to administer them to the skin as compositions or formulations, in combination with a dermatologically acceptable carrier, which may be a solid or a liquid. Useful solid carriers include finely divided solids such as talc, clay, microcrystalline cellulose, silica, alumina and the like. Useful liquid carriers include water, alcohols or glycols or water-alcohol / glycol blends, in which the present compounds can be dissolved or dispersed at effective levels, optionally with the aid of non-toxic surfactants. Adjuvants such as fragrances and antimicrobial agents can be added to optimize the properties for a given use. The resultant liquid compositions can be applied from absorbent pads, used to impregnate 1133.122WO1, SD2025-069-2PCT bandages and other dressings, or sprayed onto the affected area using pump-type or aerosol sprayers. Thickeners such as synthetic polymers, fatty acids, fatty acid salts and esters, fatty alcohols, modified celluloses or modified mineral materials can also be employed with liquid carriers to form spreadable pastes, gels, ointments, soaps, and the like, for application directly to the skin of the user. Examples of useful dermatological compositions which can be used to deliver compounds to the skin are known to the art; for example, see Jacquet et al. (U.S. Pat. No. 4,608,392), Geria (U.S. Pat. No. 4,992,478), Smith et al. (U.S. Pat. No. 4,559,157) and Wortzman (U.S. Pat. No.4,820,508). Useful dosages can be determined by comparing their in vitro activity, and in vivo activity in animal models. Methods for the extrapolation of effective dosages in mice, and other animals, to humans are known to the art; for example, see U.S. Pat. No.4,938,949. Generally, the concentration of the active compound in a liquid composition, such as a lotion, will be from about 0.1-25 wt-%, e.g., from about 0.5-10 wt-%. The concentration in a semi-solid or solid composition such as a gel or a powder will be about 0.1-5 wt-%, e.g., about 0.5-2.5 wt-%. The active ingredient may be administered to achieve peak plasma concentrations of the active compound of from about 0.5 to about 75 μM, e.g., about 1 to 50 μM, such as about 2 to about 30 μM. This may be achieved, for example, by the intravenous injection of a 0.05 to 5% solution of the active ingredient, optionally in saline, or orally administered as a bolus containing about 1-100 mg of the active ingredient. Desirable blood levels may be maintained by continuous infusion to provide about 0.01-5.0 mg / kg / hr or by intermittent infusions containing about 0.4-15 mg / kg of the active ingredient(s). The amount of the active compound, or an active salt or derivative thereof, required for use in treatment will vary not only with the particular salt selected but also with the route of administration, the nature of the condition being treated and the age and condition of the patient and will be ultimately at the discretion of the attendant physician or clinician. In general, however, a suitable dose will be in the range of from about 0.5 to about 100 mg / kg, e.g., from about 10 to about 75 mg / kg of body weight per day, such as 3 to about 50 mg per kilogram body weight of the recipient per day, for instance in the range of 6 to 90 mg / kg / day, e.g., in the range of 15 to 60 mg / kg / day. More than one dose (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28, or, for example, 35, 42, 49, 56, 63, or 70) may be determined by a physician or clinician to be required. Doses may be administered 1133.122WO1, SD2025-069-2PCT before, after, or before and after exposure to the infectious agent as determined by a physician or clinician based on the above discussed factors and other relevant factors. Scheduling of administration of doses (e.g., consecutive days, alternate days, multiple doses in one day) can also be determined by a physician or clinician based on the above discussed factors and other relevant factors. The duration of treatment can be for a predetermined period of time. For example, 1, 2, 3, 4, 5, 6, 7 or more days, one week, two weeks, three weeks, four weeks or more. Alternatively, the duration of treatment can be for a period of time until the infectious agent is no longer detectable in the subject, or the infectious agent is present at a level that does not result in symptoms or until there is an elimination or reduction in the number or severity of symptoms typically exhibited by a subject infected with a specific infectious agent. The duration of treatment can be determined by a physician or clinician based on the above discussed factors and other relevant factors. The active compounds may be conveniently administered in unit dosage form; for example, containing 5 to 1000 mg, conveniently 10 to 750 mg, most conveniently, 50 to 500 mg of active ingredient per unit dosage form. The desired dose may conveniently be presented in a single dose or as divided doses administered at appropriate intervals, for example, as two, three, four or more sub-doses per day. The sub-dose itself may be further divided, e.g., into a number of discrete loosely spaced administrations, such as multiple inhalations from an insufflator or by application of a plurality of drops into the eye. The dose, and perhaps the dose frequency, will also vary according to the age, body weight, condition, and response of the individual patient. In general, the total daily dose range for an active agent for the conditions described herein, may be from about 50 mg to about 5000 mg, in single or divided doses. In some embodiments, a daily dose range should be about 100 mg to about 4000 mg, e.g., about 1000-3000 mg, in single or divided doses, e.g., 750 mg every 6 hr of orally administered compound. This can achieve plasma levels of about 500-750 uM, which can be effective to kill cancer cells. In managing the patient, the therapy should be initiated at a lower dose and increased depending on the patient's global response. In some embodiments the compound is not administered with a solvent or preservative such as DMSO or ethanol, which may have toxic effects, e.g., in humans. The present disclosure describes various compounds useful for enhancing or prolonging an immune response, as vaccine adjuvants. EXAMPLES 1133.122WO1, SD2025-069-2PCT Various embodiments of the present invention can be better understood by reference to the following Examples which are offered by way of illustration. The present invention is not limited to the Examples provided herein. Example I - Formulation of Immune Adjuvants Introduction The formulation is important in vaccine preparation to ensure its stability and safety for clinical use. Particulate formulation can enhance the immunogenicity of vaccines through deposit effects and enhancement of uptake by antigen-presenting cells. Liposomal formulations can include spherical vesicles containing lipid derivatives, such as those currently used in human vaccines (e.g., AS01B in the Shingrix vaccine (Stoker, 2018)). Recently, lipid nanoparticles have also been used in mRNA vaccines to enhance stability and cellular entry of antigen-coding mRNA (Eygeris, 2022; Tenchov, 2021). Formulations of 1V270 Adjuvant 1V270 is a TLR7 agonist and was formulated into nanoparticles. Self-assembling 1V270 nanoparticles and lipid-incorporated 1V270 nanoparticles were biophysically characterized. Raw 1V270 nanoparticles were formulated by the drop method using DMSO and analyzed (Table 1). Namely, 1V270 self-assembling particles averaged z = 173 nm and PDI = 0.072. The incorporation rate of 1V270 into nanoparticles without added lipids was 100%. The incorporation rate of 1V270 into lipid nanoparticles was also 100%. The zeta potential of the self-assembling nanoparticles averaged -36.1 mV.

[0002] 1133.122WO1, SD2025-069-2PCT Table 1. Biophysical Characteristics of Unlipidated 1V270 Nanoparticles (50 uM sample in 1% DMSO). Liposomal formulations of 1V270 nanoparticles comprised DOPC (160 mM) and cholesterol (10 mM). 1V270 nanoparticles with DOPC-cholesterol were prepared using the lipid film rehydration method using 9:1 Chloroform:Methanol as solvents. The rehydration buffer used was 10-50mM NaPB, 100mM NaCl, pH=6.1. Sonication was employed to reduce the particle size. Liposomal formulations with either 0.05 mM 1V270 (1027-207-1) or 0.5 mM 1133.122WO1, SD2025-069-2PCT 1V270 (1027-207-2) were characterized and imaged (FIG. 10). Lipidated nanoparticles measured on average 93 nm and had PDI = 0.265. Stability of the API (1V270) in DOPC- cholesterol formulations was monitored for more than 6 months and confirmed to be greater than 98% when stored at 2-8 ℃. Aqueous formulations of 1V270 nanoparticles comprised either 0.05 mM 1V270 (1027-218-1) or 0.5 mM 1V270 (1027-218-2) in 5% Cremophor EL and were characterized and imaged (FIG.11). Formulations of 2G023A Adjuvant 2G023A is a TLR4 agonist and was formulated as an adjuvant. Some formulations were charge neutral (FIG. 9). Charge neutral formulations included liposomal, aqueous, and emulsion formulations, while charged formulations included liposomal and emulsion formulations (FIG.9). Charge-neutral liposomal formulations in DOPC-cholesterol included 4 mM 2G023A (FIG.12), such as formulation 1027-207-3. Charge-neutral aqueous formulations of 2G023A included one of the following solvent recipes: 5% TPGS, 5% TPGS + 5% DMSO, 5% Cremophor EL (such as formulation 1027-218-3 in FIG. 12, which contained 4 mM 2G023A), 5% Cremophor EL + 5% DMSO, or 1% Tween-80 + 5% DMSO. Charge-neutral emulsion formulations (FIG.9) included 5% Soybean Oil or 5% Squalene. Electrochemically charged liposomal formulations included DOPC (160 mM) and cholesterol (0-10 mM), which consequently could be cationic or anionic formulations. Electrochemically charged emulsion formulations included 5% Soybean Oil or 5% Squalene. Formulations of 2G053 Adjuvant 2G053 is a TLR4 agonist and was formulated as an adjuvant. Some formulations were charge neutral. Charge neutral formulations included liposomal formulations with DOPC (160 mM) and cholesterol (0-10 mM) (FIG.9). Formulations of 1V270 and 2G023A Co-Adjuvants Some adjuvant formulations included multiple compounds with adjuvant properties that were formulated together as co-adjuvants (FIGS. 10-12). 1V270-2G023A co-adjuvant formulations comprised either liposomal or aqueous formulations. 1V270-2G023A co- adjuvant formulations comprised either combination or admix formulations. 1V270-2G023A co-adjuvant formulations comprised liposomal combination (such as 1027-207-5 and 1027- 207-6 in FIGS.10 and 12), liposomal admix (such as with the mixing of 1027-207-1 + 1027- 207-3, or 1027-207-2 + 1027-207-3 as seen in FIGS. 12-14), aqueous combination (such as 1027-218-5 and 1027-218-6 in FIGS. 11 and 12) and aqueous admix formulations (such as with the mixing of 1027-218-1 + 1027-218-3, or 1027-218-2 + 1027-218-3 as seen in FIGS. 11-14). As will be discussed, the experiments resulting in FIGS.13-14 addressed the effects of 1133.122WO1, SD2025-069-2PCT formulation on the immunogenicity of 1V270-2G023A co-adjuvants, specifically the effects of 1V270-2G023A co-adjuvant formulation on IgG1 (FIG. 13) and IgG2 (FIG. 14) antibody titers. Formulations of 1V270 and 2E151 Co-Adjuvants Some adjuvant formulations included multiple compounds with adjuvant properties that were formulated together as co-adjuvants. 1V270-2E151 co-adjuvant formulations comprised aqueous admix formulations. An aqueous admix formulation was deemed beneficial based on the experiments regarding the effects of 1V270-2G023A co-adjuvant formulation type on immunogenicity (see FIGS.13-14). Formulations of 1V270 and 2G272 Co-Adjuvants Some adjuvant formulations included multiple compounds with adjuvant properties that were formulated together as co-adjuvants. 1V270-2G272 co-adjuvant formulations comprised aqueous admix formulations. An aqueous admix formulation was deemed beneficial based on the experiments regarding the effects of 1V270-2G023A co-adjuvant formulation type on immunogenicity (FIGS.13-14). Example 2 - Effects of Formulation on Adjuvant-Related Immunogenicity and Immunization Introduction Toll-like receptors (TLRs) recognize the pathogen-associated pattern recognition molecules, and currently, ten and thirteen TLRs are identified in humans and mice, respectively. TLR7 is located in the endosomal compartment on plasmacytoid dendritic cells and B cells in humans. In mice, TLR7 is identified in conventional dendritic cells in addition to pDC and B cells (Fitzgerald, 2020; Kawai, 2011; Fabbri, 2012). Because TLR7 is expressed in an endosomal compartment in limited immune cells and is the only TLR whose ligand is a small molecular weight compound, TLR7 ligands were selected as immune-safe and easy-to- synthesize immunomodulators for further optimization (Blasius, 2010). A synthetic TLR7 ligand, 1V136 (SM360320), was identified and an extensive structure-activity-relationship campaign was performed. Subsequently, 1V209 was identified as a versatile conjugatable TLR7 ligand (Chan, 2009). The immune-stimulatory activities of TLR7 ligands conjugated with various molecules (e.g., protein polyethylene glycol and lipids) have been explored (Chan, 2009). In vitro innate immune stimulatory effects of Lipo-1V270 Adjuvant and unformulated IV270 The lipid portion in 1V270 is incorporated into the lipid bilayers of liposomes (Andra, 2022), which attenuates the pharmacophores from accessing the receptors. Thus, the liposomal 1133.122WO1, SD2025-069-2PCT formulation was assessed to determine if lipids affected the innate immune stimulatory potency of 1V270 (FIGS. 1A-1D). Human TLR7 reporter cells (5x104cells / 200 uL / well), murine BMDC (105cells / 200 uL / well), and hPBMC (2x105cells / 200 uL / well) were cultured with serially diluted compounds. The dilution was started at 10 µM for 1V270 and Lipo-1V270, and 100 µM for 852A and 2 to 4 -fold serial dilution was performed.852A is FDA-approved TLR7 agonist and was used for comparator. LPS and blank liposome (Lipo-Blank) served as positive and negative controls, respectively. Lipo-Blank and vehicle were used for the negative control and LPS was used for positive control in some experiments. The culture supernatants were collected. NF-kB inducible SEAP protein levels in the supernatants were measured by QuantiBlue reagent, and murine IL-12 and human IL-8 in the culture supernatant was measured by ELISA. EC50and Cmaxwere calculated by Prism 10. EC50and Cmaxof unformulated 1V270 and Lipo-1V270 were compared in vitro using three cell lines; human TLR7-SEAP HEK reporter cell line, murine bone marrow-derived dendritic cells (mBMDC), and human peripheral blood mononuclear cells (hPMBC). The cells were incubated with serially diluted Lipo-1V270 or unformulated 1V270 overnight. The cytokine levels in the supernatant were measured by ELISA (FIGS.1A-1D). Dose-dependent cytokine releases are presented in FIGS. 1A-1C, and EC50and Cmaxare summarized in FIG.1D. EC50of Lipo-1V270 is higher in hTLR7 reporter cells, mBMDC, and hPBMC, while Cmaxof Lipo-1V270 shows higher trends in primary cells. These data indicate that liposomal formulation decreased the TLR7 potency of 1V270. The above in vitro study demonstrated that the formulation in liposome weakened the innate immune stimulatory potency of 1V270. However, this liposomal particulate formulation has been shown to increase the immunogenicity of vaccines by enhancing their deposit properties, which can be evaluated in in vivo experiments. As will be discussed, the liposomal formulation of 1V270 (Lipo-1V270) reduces its innate immune stimulatory potency but enhances its ability to induce antigen-specific immune responses in vivo, including increased IgG2a and IgG1 antibodies and dose-dependent adjuvant effects. Effects of 1V270-2G023A Co-Adjuvancy Formulation on Immunogenicity Various formulations of 1V270-2G023A co-adjuvants were prepared, and the effects of co-adjuvant formulation on immunogenicity were studied (FIGS. 13-14). 1V270-2G023A co-adjuvant formulations comprised liposomal combination (such as 1027-207-5 and 1027- 207-6 in FIGS.10 and 12), liposomal admix (such as with the mixing of 1027-207-1 + 1027- 207-3, or 1027-207-2 + 1027-207-3 as seen in FIGS. 12-14), aqueous combination (such as 1027-218-5 and 1027-218-6 in FIGS. 11 and 12), and aqueous admix formulations (such as 1133.122WO1, SD2025-069-2PCT with the mixing of 1027-218-1 + 1027-218-3, or 1027-218-2 + 1027-218-3 as seen in FIGS. 11-14). Experiments resulting in FIGS.13-14 explored the effects of co-adjuvant formulation on IgG1 and IgG2 antibody titer production. Specifically, FIGS.13-14 addressed the following variables affecting immune adjuvancy: (1) single adjuvant versus co-adjuvant exposure, (2) adjuvant dosage, (3) mixing of co-adjuvants to produce a chemical admix or chemical combination, (4) liposomal versus aqueous solvency. Two doses (“low” and “high”) of 1V270 were controlled for, as well as all combinations of single versus co-adjuvancy, adjuvant dose, adjuvant solvency and admix versus combination preparation. Surprisingly, aqueous admixes of 1V270-2G023A outperformed other formulations in generating a robust innate immune response in the form of IgG1 and IgG2 antibody production (FIGS.13-14). Effects of 1V270-2G023A Co-Adjuvancy Formulation on Immunization Various formulations of 1V270-2G023A co-adjuvants were prepared, and the effects of co-adjuvant formulation on immunization regimens were studied (FIGS.15A-15B and 16A- 16B). Experiments resulting in FIGS.15A-15B addressed how co-adjuvant formulation affects IgG1 and IgG2 antibody titer production in mice immunized with HA antigen in the presence of co-adjuvants 1V270-2G023A. Experiments resulting in FIGS.16A-16B addressed how co- adjuvant formulation (solvent and mixture type) affect lymphoid cell populations (specifically B and T cells) in mice that were intramuscularly immunized with HA antigen in the presence of the co-adjuvants 1V270-2G023A. Again, and similar to the data presented in FIGS.13-14, the aqueous admix formulation of 1V270-2G023A outperformed liposomal admixes and liposomal combinations (FIGS. 15A-15B, 16A-16B). Contrary to the many commercially available adjuvants that are formulated in liposomes, the immune potency of the 1V270- 2G023A co-adjuvant system is optimized as an aqueous admix formulation. Effects of Formulated Adjuvants and Co-Adjuvants on Immunogenicity and / or Immunization against Pathogens Antigen-specific immune responses by prime-boost immunization with Lipo-1V270 Adjuvant Inactivated Influenza A virus (IIVA) was used as an antigen to investigate the adjuvant effects of Lipo-1V270 and unformulated 1V270 in vivo (FIGS.2A-2F). Unformulated 1V270 induced significantly higher IgG2a but did not induce HA-specific IgG1 in sera. Lipo-1V270 adjuvanted IIAV induced HA-specific IgG1 similar to unformulated 1V270 with higher HA- specific IgG2a induction (FIGS.2B and 2C). Dose-dependent antigen-specific IgG1 and IgG2a induction by Lipo-1V270 was demonstrated using ovalbumin as an antigen (FIGS. 2D-2F). While Lipo-1V270 dropped its potency in vitro assays, these results indicated that Lipo-1V270 retained Th1 adjuvant properties similar to unformulated 1V270, and liposomal formulation 1133.122WO1, SD2025-069-2PCT provided increased Th2 adjuvant effects on 1V270 in vivo. Female BALB / c mice (6-8 week- old) (n=4-10) were i.m. immunized with IIAV (Cal9) (10µg equivalent to 3 µg HA / animal) alone, IIAV adjuvanted with unformulated 1V270, blank-liposomes (Blk-Lipo) or Lipo-1V270 on days 0 and 21. Sera were collected on day 28 and HA-specific IgG1 and G2a were measured by ELISA. Mice were i.m. immunized with OVA 1µg / animal adjuvanted with various dose of Lipo-1V270 (25, 5, 1, and 0.2 nmol / animal) on days 0 and 21. Sera were collected on day 28 and OVA-specific total IgG, IgG1 and IgG2a were measured by ELISA. P values indicated by * and ** are p<0.05 and p<0.01. respectively, by Kruskal-Wallis followed by Dunn’s test. Select formulations of 1V270 resulted in enhanced and broadened immune responses, including Th1 and Th2 responses, dose-sparing effects, heterologous protection, and increased durability. Such formulations are predicted to be particularly effective in populations that have already been vaccinated as a means of boosting these individuals by systemic or intranasal administration (mucosal).1V270 has been demonstrated to be an excellent adjuvant inducing Th1-biased immune responses but unsuitable for Th2 immune responses. Also, TLR7 expression is limited in hematopoietic cells such as plasmacytoid DCs (pDCs) and B cells. In contrast, TLR4 is expressed on immune and non-immune cells, making TLR4 ligands feasible for the priming vaccination. On the other hand, the TLR7 ligand will serve as B cell proliferation when it is used to boost immunization. Adjuvant effect of Lipo-1V270 adjuvanted IIAV boosting via the intramuscular and intranasal route following the prime immunization with MPLA adjuvanted IIAV in the heterologous prime-boost regiment It was hypothesized that TLR4 ligand and TLR7 ligand as the priming and boosting immunization would improve the magnitude and durability of the immune response, including increased T cell responses. The adjuvant activity of Lipo-1V270 was examined by heterologous prime-boost immunization with TLR4 agonist monophosphoryl Lipid A(MPLA). BALB / c were intramuscularly immunized with IIAV (10 µg / animal) adjuvanted with MPLA (1 µg / dose) or vehicle (0.5 % DMSO). The mice were then divided into 4 groups of different boosting recipes, as shown in Table 2. MPLA was used as a comparator since it is an FDA- approved vaccine adjuvant for the GSK vaccines, e.g., SHINGRIX and RSV vaccines. The animals were boosted on day 21 with the same regimen, and one cohort was sacrificed on day 28 (FIG. 3). The mice in the group of MPLA i.m.+ Lipo-1V270 i.n. received two additional boosters on days 84 and 105. The sera bronchial lavage fluid (BALF) and nasal wash (NW) were collected on days 28 and 122 (FIG 3). Influenza virus hemagglutinin-specific IgG, IgG1, IgG2a, and IgA were examined by ELISA. The splenocytes were also harvested on days 28 1133.122WO1, SD2025-069-2PCT and 122 and cultured with HA protein for five days. IL-5 and IFN-gamma in the culture supernatant were measured by ELISA. Table 2. Experimental groups for Experiments 5A, 5B, and 5C (n = 4 mice per group, n=2 cohorts). Female BALB / c mice (6–8-week-old) were immunized on days 0 and 21 (Table 2). On days 28 and 122, nasal wash and bronchial alveolar fluids were collected, and HA specific IgG and IgA were measured by ELISA (FIGS.4A-4F). P values indicated by * and ** are p<0.05 and p<0.01. respectively, by Kruskal-Wallis followed by Dunn’s test. Intramuscular vaccination with IIAV plus MPLA (i.m.) priming and Lipo-1V270 Adjuvant boosting induces mucosal HA-specific IgG and IgA To study whether Lipo-1V270 booster via i.m. and i.n. routes induced local mucosal protection, a 1st cohort of mice were sacrificed on day 42 and nasal wash and BALF were collected (FIG. 4A). Lipo-1V270 significantly enhanced HA-specific IgG in the nasal wash and BALF compared to MPLA priming alone (FIG. 4B and 4C). Intranasal boosting Lipo- 1V270 significantly increased IgA in the nasal wash (FIG.4D). These data indicated that Lipo- 1V270 adjuvanted IIAV induced local mucosal antigen-specific IgA and IgG via intramuscular routes. Lipo-1V270 adjuvant induces systemic HA-specific IgG2a comparable to MPLA i.m. boosting To examine the adjuvant effects of Lipo-1V270 on systemic IgG induction, HA- specific IgG levels in sera were measured on day 28. Intramuscular immunization of Lipo- 1V270 adjuvanted IIAV induced systemic antigen-specific total IgG at similar levels to MPLA 1133.122WO1, SD2025-069-2PCT i.m. boosted animals on day 28 (FIG.5A) and sustained up to 60 days (FIG.5B). Meanwhile, intranasal administration of Lipo-1V270 showed minimal systemic IgG release (FIG.5A). Next, it was examined whether Lipo-1V270 influences IgG1 and IG2a class switches (FIGS. 5A-5F). MPLA i.m.- Lipo-1V270 i.m. boosting induced similar levels of IgG1 with MPLA i.m.-MPLA i.m. boosting on day 28 (FIG. 5A, 5B and 5C). MPLA i.m.-MPLA i.m. boosting further increased antigen-specific antibody titers (FIG.5D and 5E). In contrast, Lipo- 1V270 i.n. boosting showed similar kinetics of IgG2a levels with MPLA i.m. boosting levels over time, while IgG2a levels decreased in the Lipo1V270 i.m. boosting group after day 89 (FIGS.5E and 5F). These trends were mirrored by the antigen-specific splenic responses, as the mice that received the Lipo-1V270 i.m. or i.n-boosting enhanced antigen-specific splenocyte responses (FIG. 5F and 5G). On day 122, 7 days after the last Lipo-1V270 i.n. boosting the antigen- specific splenic responses in 1V270 i.n. boosting group was significantly higher than those in the MPLA priming alone group (FIGS. 5H and 5I). These data indicate that the Lipo-1V270 i.n. and i.m. boosting promoted antigen-specific humoral and cellular responses when used in a heterologous prime-boost regimen. Lipo-1V270 i.n. boosting helps to maintain Th1 / / Th2 balanced cellular immune responses and could be an option for boosting in combination with existing IIAV vaccines. The cohorts of BALB / c (n=4-8) were primed with MPLA (1 µg / animal) or vehicle on day 0 as shown in FIG.3. On days 84 and 105, Lipo-1V270 i.n. group received an additional boost. Blood was collected on days 28, 42, 59, 70, 84, 91, 105, 112, and 119. HA-specific Ig were measured by ELISA. HA-specific total IgG, IgG, IgG2a, kinetics of IgG1 and IgG2a are shown in FIGS. 5A-5E. On days 28 and 122, the cohorts of mice were sacrificed and splenocytes were harvested and cultured with HA (5 µg / mL) for 3 days. HA specific IL-5 and IFN-gamma released in the culture supernatants were measured by ELISA. P values indicated by * and ** are p<0.05 and p<0.01. respectively, by Kruskal-Wallis followed by Dunn’s test. Intranasal Lipo-1V270 Adjuvant induces systemic Th1 biased immune responses The activities of unformulated 1V270 and Lipo-1V270 were compared as a mucosal adjuvant for intranasal boosting with IIAV (FIGS. 6A-6C). Both unformulated 1V270 and Lipo-1V270 induced significantly higher mucosal IgA and systemic IgG (FIG.6A and 6B). In contrast, the mice immunized with Lipo-1V270 adjuvanted IIAV produced higher IgG2a, 1133.122WO1, SD2025-069-2PCT indicating Th1 immune responses, while i.n. administration of unformulated 1V270 adjuvanted IIAV failed IgG2a induction above vehicle control (FIG.6C). The two cohorts of BALB / c (n=4-8) were primed with MPLA (1 µg / animal) or vehicle on day 0 and boosted with Lipo-1V270 or unformulated 1V270 (1V270) on days 21, 84 and 105. Nasal wash was collected on day 28. Sera were collected days 28, 42, 59, 70, 84, 91, 105, 112, and 119. HA-specific Ig were measured by ELISA, such as IgA in nasal wash. The same data of MPLA IM and MPLA IM-Lipo-1V270 in FIGS. 5D-5E are used in this comparison. The kinetics of IgG1, and IgG2a are shown in FIGS 6A-6C. P value indicated by * p<0.05 by Kruskal-Wallis followed by Dunn’s test. Lipo-1V270 Adjuvant induced cross-reactive antibodies against HA from phylogenetically distant strains The induction of cross-protective immune responses is essential to infections caused by highly mutating RNA viruses, such as influenza virus and SARS-CoV2 virus. Thus, sera were collected from mice that received H1N1 Cal9 IIAV adjuvanted Lipo-1V270 boosting (i.m. or i.n.) on day 28 and cross-reactive responses to HA of phylogenetically distant strains, H3 (group 2) and H11 (group 1), were examined (FIGS. 7A-7D). Briefly, BALB / c (n=4) were primed with MPLA (1 µg / animal, i.m.) or vehicle on day 0 and boosted with MPLA i.m. Lipo- 1V270 i.m. or Lipo-1V270 i.n. on days 21, 84 and 105. Sera collected days 28, and 112 were tested for cross reactivity against H3 and H11 HA proteins. HA-specific Ig were measured by ELISA and geometric means were calculated by Graph Pad Prism 9. On day 28, Lipo-1V270 i.m. boosting elicited H3 and H11 reactive IgG comparable to MPLA prome- boosting group (FIG. 7A and 7B). The cross-reactive Ig remained similar on days 112 (FIGS. 7C and 7D). These data demonstrate that Lipo-1V270 i.m. or i.n. boosting induced cross-reactive Ig. Lipo-1V270 Adjuvant for mRNA application The above results demonstrate that Lipo-1V270 is non-reactogenic and promotes cross- reactive IgG and IgA when administered intranasally. SARS-CoV2 mRNA protects thousands of individuals from death and severe symptoms. However, mRNA vaccines do not provide cross-reactive protection against mutated virus strains and long-term antibodies. Thus, it was hypothesized that Lipo-1V270 could address these unmet medical needs of the SARS-CoV2 mRNA vaccine. Antigen production by mRNA in a vaccine is a factor for the induction of antigen- specific humoral and cellular responses. Antigen expression in mRNA vaccines is influenced by inflammatory responses, namely type I interferons induced by LNP formulation or immune reactive nucleotides. Thus, screening commercially available TLR and non-TLR adjuvants was 1133.122WO1, SD2025-069-2PCT necessary to determine mRNA vaccine compatibility. Ovalbumin (OVA) mRNA non- replicating mRNA (nrRNA) LNP (100 ng / animal, Arcturus, San Diego, CA) were immunized with the adjuvants (Table 3), and OVA-specific IgG1 and IgG2a were measured by ELISA. MPLA and 1V270 enhanced both IgG1 and G2a (FIGS. 8A and 8B). In a repeated study, 1V270 enhanced IgG1 and G2a titers and increased OVA antigen-specific splenic IFN-gamma release (FIG. 8C, D, and 8E). Thus, it was confirmed that 1V270 and MPLA could enhance mRNA immunogenicity and have dose-sparing effects with mRNA antigen. Table 3. Adjuvants screened for OVA mRNA application. Ovalbumin non-replicating mRNA (nrRNA) LNP (100 ng / animal, Arcturus, San Diego, CA) were immunized with the indicated adjuvants (Table 3) on days 0 and 21 and OVA specific IgG 1 and IgG2a were measured by ELISA. P value indicated by * denotes p<0.05 by Kruskal Wallis test. Lipo-1V270 Adjuvant for OVA mRNA immunization regimen To evaluate the compatibility of mRNA LNP and Lipo-1V270, we combined Lipo- 1V270 (1-105 nmol / animal) with SARS-CoV-2 (Wuhan) Spike mRNA-LNP vaccine (0.5 µg / animal). BALB / c mice (n=5) were immunized with adjuvanted Spike mRNA-LNP on days 0 and 21 (Table 2, and Figure 8). On day 28, mice vaccinated with Lipo-1V270-adjuvanted mRNA-LNP showed higher levels of OVA-specific IgG1 and IgG2c when the antigen was 1133.122WO1, SD2025-069-2PCT adjuvanted with a low dose of Lipo-1V270 (1 or 1.5 nmol / dose), and increased antigen-specific antibodies to levels similar to those of high-dose mRNA-LNP (FIG. 8F). In contrast, higher doses of Lipo-1V270 (>10 nmol / dose) suppressed antibody responses (FIG. 8F). These findings suggest that low-dose Lipo-1V270 is compatible with mRNA-LNP and offer dose- sparing effects on the mRNA-LNP antigen. Table 4. Experimental groups As disclosed above, the heterologous prime-boost regimen with MPLA- and Lipo- 1V270-adjuvanted IIAV, followed by Lipo-1V270 boosting, provided multiple protective immune responses, including induction of HA-specific IgG and IgA in the nasal wash and bronchial alveolar lavage of treated mice, comparable IgG responses to MPLA prime-boost vaccination, HA-specific IgG2a and splenic T-cell responses, and cross-reactive Ig responses. Further, Lipo-1V270 demonstrated dose-sparing effects when used with mRNA antigen. Effects of 1V270-2E151 Co-Adjuvanticity on Immunogenicity Aqueous formulations of 1V270-2E151 co-adjuvants were prepared, and the effects of 1V270-2E151 co-adjuvancy on immunogenicity were studied (FIG. 17). 1V270-2E151 co- adjuvancy produced a potent IL-12 cytokine response in bone marrow-derived dendritic cells 1133.122WO1, SD2025-069-2PCT (BMDCs), in comparison to the lesser IL-12 response evoked by administration of either adjuvant individually. Effects of 1V270-2E151 Co-Adjuvancy on Immunization Aqueous formulations of 1V270-2E151 co-adjuvants were prepared, and the effects of 1V270-2E151 co-adjuvancy on a boosted intramuscular immunization regimen with OVA antigen were studied (FIGS.18A-18B).1V270-2E151 co-adjuvancy increased titers of OVA- specific IgG antibodies (FIG. 18A) and expanded lymphoid cell populations in immunized mice (B cells in FIG.18B). Effects of 1V270-2E151 Co-Adjuvancy on Immunization in organisms of advanced age Aqueous formulations of 1V270-2E151 co-adjuvants were prepared, and the effects of 1V270-2E151 co-adjuvancy on a boosted intramuscular immunization regimen with HA antigen were studied in mice of advanced age (see FIGS. 19A-19B and 20A-20B). 1V270- 2E151 co-adjuvancy increased titers of HA-specific IgG1 (FIG. 19A) and IgG2 (FIG. 19B) antibodies produced by B cells from immunized mice of advanced age. 1V270-2E151 co- adjuvancy with HA immunization induced lymphoid cell population expansion (B and T cells) in lymph nodes of aged mice, and with a similar effect size to commercial adjuvant AS01B (FIGS.20A-20B). Effects of 1V270-2G272 Co-Adjuvancy on Immunization Aqueous formulations of 1V270-2G272 co-adjuvants were prepared, and the effects of 1V270-2G272 co-adjuvancy on immunization regimens were studied. Lipo-1V270 was shown to be an excellent Th1 adjuvant, however, it was shown to be less effective for induction of Th2 immune responses. Since calcium influx inducer compound 2G272 has been demonstrated to enhance an exclusively Th2-biased immune response, 1V270 was applied as a co-adjuvant because of its Th1-biased adjuvant properties. Thus, immune responses following immunization with 2G272 mixed with TLR7 ligand (Th11V270), Alum (Th2 adjuvant), or oil and water emulsion (MF59) was studied while using IIAV as an antigen (FIGS. 21A-21E). Briefly, BALB / c mice (n=4-8) were immunized with IIAV (10 µg / animal) and adjuvanted with 1V270 (1nmol / dose), Alum (1:1) or MF59 (1:1) in the presence and absence of 2G272 (200nmol / dose) on days 0 and 21. Sera were collected on day 28 and HA-specific IgG1 and IgG2a were determined by ELISA. P values indicated by * p<0.05 and **p<0.01 by Mann- Whitney test and one way ANOVA with Kruskal Wallis test. Mice who received 2G272-adjuvanted IIAV presented with an increased HA-specific total IgG or IgG1 when used as a co-adjuvant for TLR7 ligands (1V270) (FIGS. 21A, 21B, 21C and 21D). In contrast, 2G272 had minimal effects on Alum and MF59 adjuvants.2G272 1133.122WO1, SD2025-069-2PCT demonstrated co-adjuvant activity when it was used at 200 nmol / injection (FIGS. 21D and 21E). Effects of 1V270-2G272 co-adjuvancy on a boosted intramuscular immunization regimen with IIVA were studied (FIGS. 22A-22E). 1V270-2G272 co-adjuvancy produced superior IgG and HAI titers in comparison to single adjuvant preparations administered in the presence of IIAV (FIGS.22A-22C).1V270-2G272 co-adjuvancy also promoted expansion of T and B cell populations in lymphoid organs of mice (FIGS.22D-22E). Lymphoid cells from IIAV+1V270-2G272 immunized mice produced cross-reactive IgG antibodies in the presence of antigen from phylogenetically distant strains of Influenza virus (e.g., H5, H11, H3) (FIGS. 23A-23C). Lymphoid cells from IIAV+1V270-2G272 immunized mice exposed to antigen from these Influenza strains (H1, H3, H5, and H11) also evoked robust cytokine responses for IFN-gamma and IL-17 (FIGS. 24A and 24C). P-value analysis confirmed the magnitude of IFN-gamma response was linked to 1V270-2G272 co-adjuvancy, rather than 1V270 or 2G272 adjuvancy alone, and only the commercial adjuvant AS01 could evoke a similarly robust IFN- gamma response (FIG.24B). IL-17 cytokine response was also strengthened by co-adjuvancy, but this effect could not be significantly linked to any one adjuvant or co-adjuvant system (FIG. 24D). Experiment 13: Effects of 1V270-2G272 Co-Adjuvancy on Immunization in organisms of advanced age Mice of advanced age were immunized against IIAV with 1V270-2G272 co-adjuvants (using the aqueous admix formulation). Lymphoid cells from aged, immunized mice produced robust IgG1, IgG2, and IFN-gamma responses to antigens from phylogenetically distant Influenza strains deployed in past experiments (FIGS. 25A-25F). While administration of commercially adjuvanted (AS01B and MF59) IIAV to aged mice also induced cross-reactive IgG1 and IgG2 antibody titers (FIGS. 25A-25B), only 1V270-2G272 co-adjuvanted IIAV immunization induced an IFN-gamma response during exposure to antigens from each of the four strains of Influenza tested (FIGS.25C-25F). Statements 1. An immunogenic or vaccine adjuvant composition comprising self-assembled nanoparticles of Formula (I), lipid incorporated Formula (I) nanoparticles or liposomal formulations of Formula (I) or non-liposomal nanoparticles such as aqueous dispersions, aqueous suspensions, emulsions, wherein Formula (I) comprises: 1133.122WO1, SD2025-069-2PCT wherein X1is -O-, -S-, or -NRc-; R1is hydrogen, (C1-C10)alkyl, substituted (C1-C10)alkyl, C6-10aryl, or substituted C6-10aryl, C5-9heterocyclic, or substituted C5-9heterocyclic; Rcis hydrogen, C1-10alkyl, or substituted C1-10alkyl; or Rcand R1taken together with the nitrogen to which they are attached form a heterocyclic ring or a substituted heterocyclic ring; each R2is independently -OH, (C1-C6)alkyl, substituted (C1-C6)alkyl, (C1-C6)alkoxy, substituted (C1-C6)alkoxy, -C(O)-(C1-C6)alkyl (alkanoyl), substituted -C(O)-(C1- C6)alkyl, -C(O)-(C6-C10)aryl (aroyl), substituted -C(O)-(C6-C10)aryl, -C(O)OH (carboxyl), -C(O)O(C1-C6)alkyl (alkoxycarbonyl), substituted -C(O)O(C1-C6)alkyl, -NRaRb, -C(O)NRaRb(carbamoyl), halo, nitro, or cyano, or R2is absent; each Raand Rbis independently hydrogen, (C1-C6)alkyl, substituted (C1-C6)alkyl, (C3- C8)cycloalkyl, substituted (C3-C8)cycloalkyl, (C1-C6)alkoxy, substituted (C1- C6)alkoxy, (C1-C6)alkanoyl, substituted (C1-C6)alkanoyl, aryl, aryl(C1-C6)alkyl, Het, Het (C1-C6)alkyl, or (C1-C6)alkoxycarbonyl; wherein the substituents on any alkyl, aryl or heterocyclic groups are hydroxy, C1-6alkyl, hydroxyC1-6alkylene, C1-6alkoxy, C3-6cycloalkyl, C1-6alkoxyC1-6alkylene, amino, cyano, halo, or aryl; n is 0, 1, 2, 3 or 4; X2is a bond or a linking group; and R3is a phospholipid or analog thereof comprising one or two alkyl ethers or carboxylic esters of the glyceryl moiety; or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof. wherein the composition further comprises a co-adjuvant and / or an antigen. The composition of statement 1, wherein R3comprises a group of formula: 1133.122WO1, SD2025-069-2PCT wherein: R11and R12are each independently a C8-C25 acyl group; R13is a negative charge or a hydrogen, and R14is a C1-C8n-alkyl or branched alkyl group which can be substituted or unsubstituted, wherein optionally one of the carbon atoms of the alkyl group is replaced by NH, S, or O; Z is O, S, or NH, and q is 0 or 1; the wavy line indicates a position of bonding, wherein an absolute configuration at the carbon atom bearing OR12is R, S, or any mixture thereof. 3. The composition of statement 2, wherein Z is O and q is 1. 4. The composition of statement 2, wherein R14is a C1alkyl group or a C2alkyl group. 5. The composition of any preceding statement, wherein X2is -C(O)-. 6. The composition of any preceding statement, wherein X1is O. 7. The composition of any preceding statement, wherein each R3is a C8-C25acyl group comprising one, two, three or four sites of unsaturation, epoxidation, hydroxylation, or a combination thereof. 8. The composition of statement 7, wherein each C8-C25acyl group comprises one site of unsaturation. 9. The composition of statement 8, wherein each C8-C25acyl group is of the formula: . 10. The composition of any preceding statement, wherein R1is (C1-C10)alkyl. 11. The composition of any preceding statement, wherein R2is absent. 12. The compound of statement 1, wherein the compound is of formula: 1133.122WO1, SD2025-069-2PCT . 13. The composition of any one of statements 1 to 12, wherein the nanoparticles have a Z- average of about 20-200. 14. The composition of any one of statements 1 to 13, wherein the nanoparticles have a polydispersity index (PDI) less than 0.4. 15. The composition of any one of statements 1 to 14, wherein the nanoparticles have an average zeta potential between -50 mV to 50 mV. 16. The composition of any one of statements 1 to 15, wherein the nanoparticles do not include lipids. 17. The composition of any one of statements 1 to 15, wherein the nanoparticles comprise lipids. 18. The composition of any one of statements 1 to 15 or 17, wherein the lipids are selected from phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylglycerol (PG), 1,2-dioleoyl-3- trimethylammonium-propane (DOTAP), dioleoylphosphatidylcholine (DOPC), dioleoylphosphoglycerol ( DOPG) distearoylphosphatidylcholine (DSPC), polyethylene glycol(PEG)-phospholipids, cholesterol, ionizable lipids such as D-Lin-MC3-DMA, DC- cholesterol or combinations thereof. 19. The composition of any one of statements 1 to 18, wherein the aqueous dispersions / suspensions comprise surfactants selected from Cremophor EL, Tween-80, Tween-20, SPAN-80, SPAN-83, poloxamers, TPGS, SDS, methylcellulose, PEG400, glycerol or combinations thereof. 1133.122WO1, SD2025-069-2PCT 20. The composition of any one of statements 1 to 19, wherein the emulsion comprises oils selected from squalene, soybean oil, castor oil, mineral oil, vegetable oil, sesame seed oil, linseed oil, linoleic oil or combinations thereof. 21. The composition of any one of statements 1 to 20, wherein the antigen comprises a nucleic acid sequence, an amino acid sequence / protein, a carbohydrate or an inactivated / dead or attenuated virus or bacteria or a combination thereof. 22. The composition of statement 21, wherein the nucleic acid sequence is mRNA, DNA, RNA or combination thereof. 23. The composition of statement 21 or 22, wherein the nucleic acid sequence codes for an antigenic protein. 24. The composition of any one of statements 1 to 23, wherein the antigen is an antigenic cancer, viral or bacterial protein or carbohydrate. 25. The composition of statement 21, wherein the antigen is derived from the following pathogens: a. viruses selected from Dengue, West Nile Virus, Zika fever, Coronavirus disease SARS-CoV and SARS-CoV-2, Nipah virus infection, Marburg virus, Rift Valley fever, Avian flu, Chikungunya, Ebola, Hantavirus Infection, HIV Infections, Crimean–Congo hemorrhagic fever, Influenza, Middle East respiratory syndrome, RSV, Varicella-zoster virus, Human papilloma, Hepatitis A, B, and C, Epstein Barr virus, Herpes simplex virus (Chicken- pox, Zoster), Smallpox, Foot and mouth disease virus (FMD), Measles, Mumps, Rubella, or Polio, b. bacteria selected from Tuberculosis, Cholera, Salmonella, E. coli, Pertussis, Pneumococcal disease, Gonorrhea, H. pylori infections, Anthrax, Tularemia, Streptococcus, Staphylococcus, MRSA Clostridium Difficile, Clostridium Tetani, Diphtheria or Chlamydia, or c. others selected from Lyme disease, Malaria or Syphilis. 26. The composition of statement 25, wherein the inactivated / dead or attenuated virus or bacteria is selected from a Dengue, West Nile Virus, Zika fever, Coronavirus disease 2019, Nipah virus infection, Marburg virus, Rift Valley fever, Avian flu, Chikungunya, Ebola, Hantavirus Infection, HIV Infections, SARS-CoV and SARS-CoV-2, Crimean–Congo hemorrhagic fever, Influenza, Middle East respiratory syndrome, RSV, Varicella-zoster virus, Human papilloma, Hepatitis A, B, and C, Epstein Barr virus, HSV 1,2,6, Smallpox virus or combination thereof. 1133.122WO1, SD2025-069-2PCT 27. The composition of any one of statements 21 to 26, wherein the viral protein is a spike or capsid protein. 28. The composition of any one of statements 1 to 27, further comprising an additional adjuvant. 29. The composition of statement 28, wherein the additional adjuvant comprises one or more of aluminum salts, 3-O-desacyl-4’-monophosphoryl lipid A (MPL), an oil-in-water emulsion of squalene oil, CpG 1018, AS04, AS01, a saponin adjuvant derived from Quillaja saponaria (QS21) or an oil-in-water emulsion containing squalene and vitamin E (ASO3). 30. The composition of any one of statements 1 to 29, wherein the co-adjuvant is formulated as nanoparticles. 31. The composition of statement 30, wherein the co-adjuvant is selected from Formula (II), (III), (IV), (V), or (VI): (Formula (II)), or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R15is selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R16and R17are each independently selected from -Br, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; and R18is selected from substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl; 1133.122WO1, SD2025-069-2PCT (Formula (III)) or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R19is hydrogen, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R20is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; and R21is -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or (Formula (IV)) or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R22is hydrogen, halogen, -CN, -SH, -OH, -COOH, -NH2, -CONH2, nitro, -CF3, - CCl3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; R23is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 1133.122WO1, SD2025-069-2PCT R24is substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl; and R25is halogen, -CN, -SH, -OH, -COOH, -NH2, -CONH2, -NO2, -CF3, -CCl3, -PO4, substituted and unsubstituted phosphates, -SO4, substituted and unsubstituted alkyls, substituted and unsubstituted alkenes, substituted and unsubstituted alkynes, azides, esters, amides, ethers including substituted and unsubstituted alkyls, lipids, phospholipids, PEGs, linkers not limited to substituted carbonates, substituted carbamates and oxalate, succinate. 32. The composition of statement 30, wherein the co-adjuvant is selected from Formula (V), (VI) or (VII): (Formula (V)) or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R26and R27are each independently selected from -Br, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; R28is selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and G is S or Se; 1133.122WO1, SD2025-069-2PCT (Formula (VI)) or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R29is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R30is H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, -NH2or -OH; or or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R31is hydrogen, halogen, -CN, -SH, -OH, -COOH, -NH2, -CONH2, nitro (NO2), -CF3, -CCl3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; and R32is H; OR32A, wherein R32Ais H, substituted or unsubstituted alkyl, substituted or unsubstituted alkynyl or substituted or unsubstituted alkenyl; or NHR32B, wherein R32Bis H or acyl. The composition of statement 30, wherein the co-adjuvant is selected from: 1133.122WO1, SD2025-069-2PCT or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof. 34. The composition of any one of statements 1 to 33, wherein the composition is formulated as a nanoparticle, a micelle, an emulsion or an aqueous dispersion / suspension formulation. 35. The composition of any one of statements 1 to 34, wherein the composition is formulated as a neutral formulation. 36. The composition of any one of statements 1 to 34, wherein the composition is formulated as a charged formulation. 37. The composition of any one of statements 1 to 36, wherein the composition is formulated as a co-encapsulated formulation. 38. The composition of any one of statements 1 to 37, wherein the composition comprising Formula (I) and the co-adjuvant are co-encapsulated within a single nanoparticle. 39. The composition of any one of claims 1 to 36, wherein the composition is formulated as an admixed composition. 40. The composition of any one of statements 1 to 36 or 39, wherein the composition comprising Formula (I) and the co-adjuvant are present as an admix of separate nanoparticles. 41. The composition of statement 39 or 40, wherein the composition is formulated as an aqueous admix of Formula (I) and Formula (II), or Formula (III), or Formula (IV), or Formula (V), Formula (VI) or Formula (VII). 1133.122WO1, SD2025-069-2PCT 42. A method to produce an immune response in a subject comprising administering to the subject an effective amount of a composition of any one of statements 1 to 41. 43. A method to enhance or prolong an antigen immune response in a subject comprising administering to the subject an effective amount of a composition of any one of statements 1 to 41. 44. A method to boost a primary vaccination in a subject comprising administering to the subject an effective amount of a composition of any one of statements 1 to 41. 45. The method of any one of statements 42 to 44, wherein the subject is of 55 or more years old. 46. The method of any one of statements 42 to 45, wherein the subject is immunocompromised. 47. The method of any one of statements 42 to 46, wherein the administration is systemic or mucosal. 48. The method of statement 47, wherein the mucosal administration is intranasal (i.n.). 49. The method of any one of statements 42 to 47, wherein the administration is intramuscular (i.m.), subcutaneous (s.c.) or intradermal (i.d.). Bibliography 1. Stoker K, Levien TL, Baker DE. Zoster Vaccine Recombinant, Adjuvanted. Hosp Pharm. 2018;53(3):136-41. Epub 2018 / 08 / 28. 2. Eygeris Y, Gupta M, Kim J, Sahay G. Acc Chem Res.2022;55(1):2-12. 3. Tenchov R, Bird R, Curtze AE, Zhou Q. ACS Nano.2021;15(11):16982-7015. 4. Fitzgerald KA, Kagan JC. Cell.2020;180(6):1044-66. 5. Kawai T, Akira S. Immunity.2011;34(5):637-50. 6. Fabbri M. Cancer Res.2012;72(24):6333-7. 7. Blasius AL, Beutler B. Immunity.2010;32(3):305-15. 8. Chan M, Hayashi T, Kuy CS, Gray CS, Wu CC, Corr M, Wrasidlo W, Cottam HB, Carson DA. Bioconjug Chem.2009;20(6):1194-200. 9. Chan M, Hayashi T, Mathewson RD, Yao S, Gray C, Tawatao RI, Kalenian K, Zhang Y, Hayashi Y, Lao FS, Cottam HB, Carson DA. Bioconjug Chem.2011;22(3):445-54. 10. Hayashi T, Chan M, Norton JT, Wu CC, Yao S, Cottam HB, Tawatao RI, Corr M, Carson DA, Daniels GA. Melanoma Res.2011;21(1):66-75. 11. Sato-Kaneko F, Yao S, Lao FS, Sako Y, Jin J, Shukla NM, Cottam HB, Chan M, Belsuzarri MM, Carson DA, Hayashi T. Vaccines (Basel).2022;10(10). 1133.122WO1, SD2025-069-2PCT 12. Sato-Kaneko F, Yao S, Lao FS, Shpigelman J, Messer K, Pu M, Shukla NM, Cottam HB, Chan M, Chu PJ, Burkhart D, Schoener R, Matsutani T, Carson DA, Corr M, Hayashi T. Front Immunol.2020;11:1207. 13. Goff PH, Hayashi T, He W, Yao S, Cottam HB, Tan GS, Crain B, Krammer F, Messer K, Pu M, Carson DA, Palese P, Corr M. J Virol.2017;91(19). 14. Goff PH, Hayashi T, Martinez-Gil L, Corr M, Crain B, Yao S, Cottam HB, Chan M, Ramos I, Eggink D, Heshmati M, Krammer F, Messer K, Pu M, Fernandez-Sesma A, Palese P, Carson DA. J Virol.2015;89(6):3221-35. 15. Andra V, Pammi SVN, Bhatraju L, Ruddaraju LK. Bionanoscience.2022;12(1):274-91. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Exemplary methods and materials are described herein, although methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention. Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific substances and procedures described herein. Such equivalents are considered to be within the scope of this invention. All publications, patents, and patent applications, Genbank sequences, websites and other published materials referred to throughout the disclosure herein are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application, Genbank sequences, websites and other published materials was specifically and individually indicated to be incorporated by reference. In the event that the definition of a term incorporated by reference conflicts with a term defined herein, this specification shall control.

Claims

1133.122WO1, SD2025-069-2PCT WHAT IS CLAIMED IS:

1. An immunogenic or vaccine adjuvant composition comprising self-assembled nanoparticles of Formula (I), lipid incorporated Formula (I) nanoparticles or liposomal formulations of Formula (I) or non-liposomal nanoparticles such as aqueous dispersions, aqueous suspensions, emulsions, wherein Formula (I) comprises:wherein X1is -O-, -S-, or -NRc-; R1is hydrogen, (C1-C10)alkyl, substituted (C1-C10)alkyl, C6-10aryl, or substituted C6-10aryl, C5-9heterocyclic, or substituted C5-9heterocyclic; Rcis hydrogen, C1-10alkyl, or substituted C1-10alkyl; or Rcand R1taken together with the nitrogen to which they are attached form a heterocyclic ring or a substituted heterocyclic ring; each R2is independently -OH, (C1-C6)alkyl, substituted (C1-C6)alkyl, (C1-C6)alkoxy, substituted (C1-C6)alkoxy, -C(O)-(C1-C6)alkyl (alkanoyl), substituted -C(O)-(C1- C6)alkyl, -C(O)-(C6-C10)aryl (aroyl), substituted -C(O)-(C6-C10)aryl, -C(O)OH (carboxyl), -C(O)O(C1-C6)alkyl (alkoxycarbonyl), substituted -C(O)O(C1-C6)alkyl, -NRaRb, -C(O)NRaRb(carbamoyl), halo, nitro, or cyano, or R2is absent; each Raand Rbis independently hydrogen, (C1-C6)alkyl, substituted (C1-C6)alkyl, (C3- C8)cycloalkyl, substituted (C3-C8)cycloalkyl, (C1-C6)alkoxy, substituted (C1- C6)alkoxy, (C1-C6)alkanoyl, substituted (C1-C6)alkanoyl, aryl, aryl(C1-C6)alkyl, Het, Het (C1-C6)alkyl, or (C1-C6)alkoxycarbonyl; wherein the substituents on any alkyl, aryl or heterocyclic groups are hydroxy, C1-6alkyl, hydroxyC1-6alkylene, C1-6alkoxy, C3-6cycloalkyl, C1-6alkoxyC1-6alkylene, amino, cyano, halo, or aryl; n is 0, 1, 2, 3 or 4; X2is a bond or a linking group; and1133.122WO1, SD2025-069-2PCT R3is a phospholipid or analog thereof comprising one or two alkyl ethers or carboxylic esters of the glyceryl moiety; or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof. wherein the composition further comprises a co-adjuvant and / or an antigen.

2. The composition of claim 1, wherein R3comprises a group of formula:wherein: R11and R12are each independently a C8-C25acyl group; R13is a negative charge or a hydrogen, and R14is a C1-C8n-alkyl or branched alkyl group which can be substituted or unsubstituted, wherein optionally one of the carbon atoms of the alkyl group is replaced by NH, S, or O; Z is O, S, or NH, and q is 0 or 1; the wavy line indicates a position of bonding, wherein an absolute configuration at the carbon atom bearing OR12is R, S, or any mixture thereof.

3. The composition of claim 2, wherein Z is O and q is 1.

4. The composition of claim 2, wherein R14is a C1alkyl group or a C2alkyl group.

5. The composition of claim 1, wherein X2is -C(O)-.

6. The composition of claim 1, wherein X1is O.

7. The composition of claim 1, wherein each R3is a C8-C25acyl group comprising one, two, three or four sites of unsaturation, epoxidation, hydroxylation, or a combination thereof.

8. The composition of claim 7, wherein each C8-C25acyl group comprises one site of unsaturation.

9. The composition of claim 8, wherein each C8-C25acyl group is of the formula:1133.122WO1, SD2025-069-2PCT.

10. The composition of claim 1, wherein R1is (C1-C10)alkyl.

11. The composition of claim 1, wherein R2is absent.

12. The compound of claim 1, wherein the compound is of formula:.

13. The composition of claim 1, wherein the nanoparticles have a Z-average of about 20- 200.

14. The composition of claim 1, wherein the nanoparticles have a polydispersity index (PDI) less than 0.

4.

15. The composition of claim 1, wherein the nanoparticles have an average zeta potential between -50 mV to 50 mV.

16. The composition of claim 1, wherein the nanoparticles do not include lipids.

17. The composition of claim 1, wherein the nanoparticles comprise lipids.1133.122WO1, SD2025-069-2PCT 18. The composition of claim 1, wherein the lipids are selected from phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylglycerol (PG), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), dioleoylphosphatidylcholine (DOPC), dioleoylphosphoglycerol ( DOPG) distearoylphosphatidylcholine (DSPC), polyethylene glycol(PEG)-phospholipids, cholesterol, ionizable lipids such as D-Lin-MC3-DMA, DC-cholesterol or combinations thereof.

19. The composition of claim 1, wherein the aqueous dispersions / suspensions comprises surfactants selected from Cremophor EL, Tween-80, Tween-20, SPAN-80, SPAN-83, poloxamers, TPGS, SDS, methylcellulose, PEG400, glycerol or combinations thereof.

20. The composition of claim 1, wherein the emulsion comprises oils selected from squalene, soybean oil, castor oil, mineral oil, vegetable oil, sesame seed oil, linseed oil, linoleic oil or combinations thereof.

21. The composition of claims 1, wherein the antigen comprises a nucleic acid sequence, an amino acid sequence / protein, a carbohydrate or an inactivated / dead or attenuated virus or bacteria or a combination thereof.

22. The composition of claim 21, wherein the nucleic acid sequence is mRNA, DNA, RNA or combination thereof.

23. The composition of claim 21, wherein the nucleic acid sequence codes for an antigenic protein.

24. The composition of claim 1, wherein the antigen is an antigenic cancer, viral or bacterial protein or carbohydrate.

25. The composition of claim 21, wherein the antigen is derived from the following pathogens: a. viruses selected from Dengue, West Nile Virus, Zika fever, Coronavirus disease SARS-CoV and SARS-CoV-2, Nipah virus infection, Marburg virus, Rift Valley fever, Avian flu, Chikungunya, Ebola, Hantavirus Infection, HIV Infections, Crimean–Congo hemorrhagic fever, Influenza, Middle East respiratory syndrome, RSV, Varicella-zoster virus,1133.122WO1, SD2025-069-2PCT Human papilloma, Hepatitis A, B, and C, Epstein Barr virus, Herpes simplex virus (Chicken- pox, Zoster), Smallpox, Foot and mouth disease virus (FMD), Measles, Mumps, Rubella, or Polio, b. bacteria selected from Tuberculosis, Cholera, Salmonella, E. coli, Pertussis, Pneumococcal disease, Gonorrhea, H. pylori infections, Anthrax, Tularemia, Streptococcus, Staphylococcus, MRSA Clostridium Difficile, Clostridium Tetani, Diphtheria or Chlamydia, or c. others selected from Lyme disease, Malaria or Syphilis.

26. The composition of claim 25, wherein the inactivated / dead or attenuated virus or bacteria is selected from a Dengue, West Nile Virus, Zika fever, Coronavirus disease 2019, Nipah virus infection, Marburg virus, Rift Valley fever, Avian flu, Chikungunya, Ebola, Hantavirus Infection, HIV Infections, SARS-CoV and SARS-CoV-2, Crimean–Congo hemorrhagic fever, Influenza, Middle East respiratory syndrome, RSV, Varicella-zoster virus, Human papilloma, Hepatitis A, B, and C, Epstein Barr virus, HSV 1,2,6, Smallpox virus or combination thereof.

27. The composition of claim 21, wherein the viral protein is a spike or capsid protein.

28. The composition of claim 1, further comprising an additional adjuvant.

29. The composition of claim 28, wherein the additional adjuvant comprises one or more of aluminum salts, 3-O-desacyl-4’-monophosphoryl lipid A (MPL), an oil-in-water emulsion of squalene oil, CpG 1018, AS04, AS01, a saponin adjuvant derived from Quillaja saponaria (QS21) or an oil-in-water emulsion containing squalene and vitamin E (ASO3).

30. The composition of claim 1, wherein the co-adjuvant is formulated as nanoparticles.

31. The composition of claim 30, wherein the co-adjuvant is selected from Formula (II), (III), (IV), (V), or (VI):1133.122WO1, SD2025-069-2PCT(Formula (II)), or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R15is selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R16and R17are each independently selected from -Br, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; and R18is selected from substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;(Formula (III)) or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R19is hydrogen, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R20is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; and1133.122WO1, SD2025-069-2PCT R21is -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or(Formula (IV)) or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R22is hydrogen, halogen, -CN, -SH, -OH, -COOH, -NH2, -CONH2, nitro, -CF3, - CCl3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; R23is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R24is substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl; and R25is halogen, -CN, -SH, -OH, -COOH, -NH2, -CONH2, -NO2, -CF3, -CCl3, -PO4, substituted and unsubstituted phosphates, -SO4, substituted and unsubstituted alkyls, substituted and unsubstituted alkenes, substituted and unsubstituted alkynes, azides, esters, amides, ethers including substituted and unsubstituted alkyls, lipids, phospholipids, PEGs, linkers not limited to substituted carbonates, substituted carbamates and oxalate, succinate.

32. The composition of claim 30, wherein the co-adjuvant is selected from Formula (V), (VI) or (VII):1133.122WO1, SD2025-069-2PCT(Formula (V)) or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R26and R27are each independently selected from -Br, -OH, -NH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; R28is selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and G is S or Se;(Formula (VI)) or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R29is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R30is H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, -NH2or -OH; or1133.122WO1, SD2025-069-2PCTor a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein: R31is hydrogen, halogen, -CN, -SH, -OH, -COOH, -NH2, -CONH2, nitro (NO2), -CF3, -CCl3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkenyl and substituted or unsubstituted heteroalkenyl; and R32is H; OR32A, wherein R32Ais H, substituted or unsubstituted alkyl, substituted or unsubstituted alkynyl or substituted or unsubstituted alkenyl; or NHR32B, wherein R32Bis H or acyl.

33. The composition of claim 30, wherein the co-adjuvant is selected from:1133.122WO1, SD2025-069-2PCT or a tautomer thereof; or a pharmaceutically acceptable salt or solvate thereof.

34. The composition of claim 1, wherein the composition is formulated as a nanoparticle, a micelle, an emulsion or an aqueous dispersion / suspension formulation.

35. The composition of claim 1, wherein the composition is formulated as a neutral formulation.

36. The composition of any one of claims 1 to 34, wherein the composition is formulated as a charged formulation.

37. The composition of claim 1, wherein the composition is formulated as a co- encapsulated formulation.

38. The composition of claim 1, wherein the composition comprising Formula (I) and the co-adjuvant are co-encapsulated within a single nanoparticle.

39. The composition of claim 1, wherein the composition is formulated as an admixed composition.

40. The composition of claim 1, wherein the composition comprising Formula (I) and the co-adjuvant are present as an admix of separate nanoparticles.

41. The composition of claim 39, wherein the composition is formulated as an aqueous admix of Formula (I) and Formula (II), or Formula (III), or Formula (IV), or Formula (V), Formula (VI) or Formula (VII).

42. A method to produce an immune response in a subject comprising administering to the subject an effective amount of a composition of claim 1.

43. A method to enhance or prolong an antigen immune response in a subject comprising administering to the subject an effective amount of a composition of claim 1.1133.122WO1, SD2025-069-2PCT 44. A method to boost a primary vaccination in a subject comprising administering to the subject an effective amount of a composition of claim 1.

45. The method of claim 42, wherein the subject is of 55 or more years old.

46. The method of claim 42, wherein the subject is immunocompromised.

47. The method of claim 42, wherein the administration is systemic or mucosal.

48. The method of claim 47, wherein the mucosal administration is intranasal (i.n.).

49. The method of claim 42, wherein the administration is intramuscular (i.m.), subcutaneous (s.c.) or intradermal (i.d.).

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