Related U.S. Application Data 9 страница

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some embodiments, the subject has been exposed to or may be exposed to a toxin from a hazardous environmental substance. In some embodiments, the nanocarrier comprises a В-cell antigen, an immuno stimulatory agent, and a T cell antigen, such as an universal T cell antigen. In some embodiments, the nanocarrier further comprises a targeting moiety.

In some embodiments, where the method is for treating or preventing an addiction (or for treating a subject exposed to or who may be exposed to a toxin), the nanocarrier com­prises the addictive substance or toxin, an adjuvant, and a T cell. In some embodiments, the method raises high titer antibodies that bind and neutralize the offending agent before it reaches its effector site (e. g., the brain). In some embodiments, the addictive substance or toxin is at a high density on the surface of the nanocarrier.

In some embodiments, the infectious disease is a chronic viral infection. In some embodiments, the chronic viral infection is HIV, HPV, HBV, or HCV infection. In some embodiments, the infectious disease is or is caused by a bacterial infection. In some embodiments, the subject has or is susceptible to having a Pseudomonas infection, a Pneu­mococcus infection, tuberculosis, malaria, leishmaniasis, H. pylori, a Staphylococcus infection, or a Salmonella infec­tion. In some embodiments, the infectious disease is or is caused by a fungal infection. In some embodiments, the infectious disease is or is caused by a parasitic infection. In some embodiments, the infectious disease is or is caused by a protozoan infection. In some embodiments, the subject has or is susceptible to having influenza.

In some embodiments, where the method is to suppress or redirect an immune response, the subject has or is suscep­tible to having an allergic disease or an autoimmune disease. In some embodiments, the subject has a food allergy. In some embodiments, the subject is allergic to milk or other milk components (e. g., lactose), eggs, peanuts, tree nuts (walnuts, cashews, etc. ), fish, shellfish, soy, or wheat. In some embodiments, the method is to tolerize a subject to an antigen, such as an allergen. In some embodiments, the autoimmune disease is disease is lupus, multiple sclerosis, rheumatoid arthritis, diabetes mellitus type I, inflammatory bowel disease, thyroiditis, or celiac disease. In some embodiments, the subject has had or will have a transplant, and the method can be to prevent or ameliorate transplant rejection. In some embodiments, the nanocarrier comprises an antigen and an immune suppressant or an agent that induces regulatory T cells. In some embodiments, the nano­carrier further comprises a targeting moiety. Generally, where the method is one to suppress an immune response, the antigen is provided in the absence of an adjuvant.

In some embodiments for treating an allergy, the nano­carrier includes an allergen and an immunostimulatory agent (such as an adjuvant, e. g., a TLR agonist).

In some embodiments, the composition is administered in an amount effective to modify an immune response (e. g., from a Th2 to a Thl immune response). In some embodi­ments, the subject has or is susceptible to having an allergic disease. In some embodiments, the nanocarrier comprises an antigen, such as an allergen, and an immuno stimulatory agent. In some embodiments, the nanocarrier further com­prises a targeting moiety.

In some aspects, vaccine nanocarriers for delivery of immunomodulatory agents to the cells of the immune sys­tem are provided. In some embodiments, vaccine nanocar­riers comprise at least one immunomodulatory agent that is capable of inducing an immune response in В cells and/or in T cells. In certain embodiments, immunomodulatory agents

presented on nanocarrier surfaces stimulate В cells, and immunomodulatory agents encapsulated within the nanocar­riers are processed and presented to T cells. In some embodi­ments, vaccine nanocarriers comprise at least one targeting moiety that is useful for selective delivery of the vaccine nanocarrier to specific antigen-presenting cells (APCs).

In some embodiments, an immunomodulatory agent may comprise isolated and/or recombinant proteins or peptides, carbohydrates, glycoproteins, glycopeptides, proteoglycans, inactivated organisms and viruses, dead organisms and virus, genetically altered organisms or viruses, and cell extracts. In some embodiments, an immunomodulatory agent may comprise nucleic acids, carbohydrates, lipids, and/or small molecules. In some embodiments, an immu­nomodulatory agent is one that elicits an immune response. In some embodiments, an immunomodulatory agent is an antigen. In some embodiments, an immunomodulatory agent is used for vaccines.

In some embodiments, an immunomodulatory agent is any protein and/or other antigen derived from a pathogen. The pathogen may be a virus, bacterium, fungus, protozoan, parasite, etc. In some embodiments, an immunomodulatory agent may be in the form of whole killed organisms, peptides, proteins, glycoproteins, glycopeptides, proteogly­cans, carbohydrates, or combinations thereof.

In some embodiments, all of the immunomodulatory agents of a vaccine nanocarrier are identical to one another. In some embodiments, all of the immunomodulatory agents of a vaccine nanocarrier are different. In some embodiments, a vaccine nanocarrier comprises exactly one distinct type (i. e., species) of immunomodulatory agent. For example, when the immunomodulatory agent is an antigen, all of the antigens that are in the vaccine nanocarrier are the same. In some embodiments, a vaccine nanocarrier comprises exactly two distinct types of immunomodulatory agents. In some embodiments, a vaccine nanocarrier comprises greater than two distinct types of immunomodulatory agents.

In some embodiments, a vaccine nanocarrier comprises a single type of immunomodulatory agent that stimulates an immune response in В cells. In some embodiments, a vaccine nanocarrier comprises a single type of immuno­modulatory agent that stimulates an immune response in T cells. In some embodiments, a vaccine nanocarrier com­prises two types of immunomodulatory agents, wherein the first immunomodulatory agent stimulates В cells, and the second immunomodulatory agent stimulates T cells. In certain embodiments, any of the aforementioned agents could stimulate both В cells and T cells, but this is not necessarily so. In certain embodiments, the aforementioned immunomodulatory agents stimulates only В cells orT cells, respectively. In some embodiments, a vaccine nanocarrier comprises greater than two types of immunomodulatory agents, wherein one or more types of immunomodulatory agents stimulate В cells, and one or more types of immu­nomodulatory agents stimulate T cells.

In some embodiments, a vaccine nanocarrier includes a lipid membrane (e. g. lipid bilayer, lipid monolayer, etc. ). At least one immunomodulatory agent may be associated with the lipid membrane. In some embodiments, at least one immunomodulatory agent is embedded within the lipid membrane, embedded within the lumen of a lipid bilayer, associated with the interior surface of the lipid membrane, and/or encapsulated with the lipid membrane of a vaccine nanocarrier.

In some embodiments, a vaccine nanocarrier includes a polymer (e. g. a polymeric core). The immunomodulatory agent may be associated with the polymer, and in some

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embodiments, at least one type of immunomodulatory agent is associated with the polymer. In some embodiments, the immunomodulatory agent is embedded within the polymer, associated with the interior surface of the polymer, and/or encapsulated within the polymer of a vaccine nanocarrier, and, in some embodiments, at least one type of immuno­modulatory agent is embedded within the polymer, associ­ated with the interior surface of the polymer, and/or encap­sulated within the polymer of a vaccine nanocarrier.

In some embodiments, inventive vaccine nanocarriers comprise less than less than 90% by weight, less than 75% by weight, less than 50% by weight, less than 40% by weight, less than 30% by weight, less than 20% by weight, less than 15% by weight, less than 10% by weight, less than 5% by weight, less than 1% by weight, or less than 0. 5% by weight of the immunomodulatory agent.

In some embodiments, vaccine nanocarriers are associ­ated with at least one targeting moiety. In some embodi­ments, a targeting moiety may be a nucleic acid, polypep­tide, peptide, glycoprotein, glycopeptide, proteoglycan, carbohydrate, lipid, small molecule, etc. For example, a targeting moiety can be a nucleic acid targeting moiety (e. g. an aptamer, Spiegelmer®, etc. ) that binds to a cell type specific marker. In some embodiments, a targeting moiety may be a naturally occurring or synthetic ligand for a cell surface protein, e. g., DEC-205, CD169, CDllb, etc. Examples of targeting moieties also include those provided elsewhere herein, such as those described above.

In accordance with the present invention, a targeting moiety recognizes one or more “targets” or “markers” associated with a particular organ, tissue, cell, and/or sub- cellular locale. In some embodiments, a target may be a marker that is exclusively or primarily associated with one or a few cell types, with one or a few diseases, and/or with one or a few developmental stages. Examples of cells that are targeted include antigen presenting cells (APCs), such as dendritic cells, follicular dendritic cells, and macrophages. One example of a macrophage is a subcapsular sinuc mac­rophage. Other cells that are targeted include T cells and В cells. In some embodiments, a target can comprise a protein, a carbohydrate, a lipid, and/or a nucleic acid. In some embodiments, a target is a tumor marker. In some embodi­ments, a target is an APC marker. In certain embodiments, a target is a T cell marker. In some embodiments, the targeting moieties target secondary lymphoid tissues or organs. Secondary lympoid tissues or organs include lymph nodes, the spleen, Peyer’s patches, the appendix, or tonsils.

In certain embodiments, a target is a dendritic cell marker. In some embodiments, DC markers include DC-205, CDllc, class II MHC, CD80, CD86, DC-SIGN, CDllb, BDCA-1, BDCA-2, BDCA-4, Siglec-H, CX3CR1, and/or Langerin. Examples of such markers are provided elsewhere herein.

In certain embodiments, a target is a subcapsular sinus macrophage marker. In some embodiments, SCS-Mph markers include CD169 (i. e. sialoadhesin), CDllb (i. e. CDllb/CD18, Mac-1, CR3 or < iM|> 2 integrin), Fc receptor, and/or the mannose receptor (i. e. a multi-valent lectin), proteins which are all prominently expressed on SCS-Mph. Examples of such markers are provided elsewhere herein.

In certain embodiments, a target is a В cell marker. In some embodiments, В cell markers may include comple­ment receptors, CR1 (i. e. CD35) or CR2 (i. e. CD21), proteins which are expressed on В cells. In some embodi­ments, В cell targeting can be accomplished by В cell markers such as CD19, CD20, and/or CD22. In some embodiments, В cell targeting can be accomplished by В

cell markers such as CD40, CD52, CD80, CXCR5, VLA-4, class II MHC, surface IgM or IgD, APRL, and/or BAFF-R. Examples of such markers are provided elsewhere herein.

In certain embodiments, a target is a FDC marker. In some embodiments, FDC markers include complement receptors, CR1 (i. e. CD35) or CR2 (i. e. CD21), proteins which are expressed on FDCs. Examples of such markers are provided elsewhere herein.

In some embodiments, a vaccine nanocarrier comprises a single type of targeting moiety that directs delivery of the vaccine nanocarrier to a single cell type (e. g. delivery to SCS-Mph only). In some embodiments, a vaccine nanocar­rier comprises a single type of targeting moiety that directs delivery of the vaccine nanocarrier to multiple cell types (e. g. delivery to both SCS-Mphs and FDCs, or to both SCS-Mphs and DCs). In some embodiments, a vaccine nanocarrier comprises two types of targeting moieties, wherein the first type of targeting moiety directs delivery of the vaccine nanocarrier to one cell type, and the second type of targeting moiety directs delivery of the vaccine nanocar­rier to a second cell type. For example, in some embodi­ments, the first type of targeting moiety directs delivery to SCS-Mphs, and the second type of targeting moiety directs delivery to DCs. As another example, the first type of targeting moiety directs delivery to SCS-Mphs, and the second type of targeting moiety directs delivery to FDCs.

In some embodiments, inventive vaccine nanocarriers comprise less than 50% by weight, less than 40% by weight, less than 30% by weight, less than 20% by weight, less than 15% by weight, less than 10% by weight, less than 5% by weight, less than 1% by weight, or less than 0. 5% by weight of the targeting moiety.

In some embodiments, vaccine nanocarriers may trans­port one or more types of immuno stimulatory agents which can help stimulate immune responses. In some embodi­ments, immunostimulatory agents boost immune responses by activating APCs to enhance their immuno stimulatory capacity. In some embodiments, immuno stimulatory agents boost immune responses by amplifying lymphocyte responses to specific antigens. In some embodiments, immu­nostimulatory agents boost immune responses by inducing the local release of mediators, such as cytokines from a variety of cell types.

In some embodiments, a vaccine nanocarrier comprises a single type of immuno stimulatory agent that stimulates both В cells and T cells. In some embodiments, a vaccine nanocarrier comprises two types of immuno stimulatory agents, wherein the first type of immuno stimulatory agent stimulates В cells, and the second type of immunostimula­tory agent stimulates T cells. In some embodiments, a vaccine nanocarrier comprises greater than two types of immuno stimulatory agents, wherein one or more types of immuno stimulatory agents stimulate В cells, and one or more types of immuno stimulatory agents stimulate T cells.

In some embodiments, various assays can be utilized in order to determine whether an immune response has been modulated in a В cell or group of В cells or in a T cell or group of T cells. In some embodiments, the assay assesses whether or not the cell or group of cells has/have become “activated”.

In some embodiments, various assays can be utilized in order to determine whether an immune response has been stimulated in a T cell or group of T cells. In some embodi­ments, stimulation of an immune response in T cells can be determined by measuring antigen-induced production of cytokines by T cells. In some embodiments, stimulation of an immune response in T cells can be determined by

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21 measuring antigen-induced proliferation of T cells. In some embodiments, an immune response in T cells is determined to be stimulated if cellular markers of T cell activation are expressed at different levels (e. g. higher or lower levels) relative to unstimulated cells.

In some embodiments, various assays can be utilized in order to determine whether an immune response has been stimulated in a В cell or group of В cells. In some embodi­ments, stimulation of an immune response in В cells can be determined by measuring antibody titers, antibody affinities, antibody performance in neutralization assays, class-switch recombination, affinity maturation of antigen-specific anti­bodies, development of memory В cells, development of long-lived plasma cells that can produce large amounts of high-affinity antibodies for extended periods of time, ger­minal center reactions, and/or antibody performance in neutralization assays.

A vaccine nanocarrier is an entity that comprises, for example, at least one immunomodulatory agent which is capable of stimulating an immune response in В cells and/or T cells. Any vaccine nanocarrier can be used in accordance with the present invention.

In some embodiments, a nanocarrier has a greatest dimen­sion (e. g., diameter) of less than 100 microns (pm). In some embodiments, inventive nanocarriers have a greatest dimen­sion (e. g., diameter) of 300 nm or less. In some embodi­ments, inventive nanocarriers have a greatest dimension (e. g., diameter) of 250 nm or less. In some embodiments, inventive nanocarriers have a greatest dimension (e. g., diameter) of 200 nm or less. In some embodiments, inven­tive nanocarriers have a greatest dimension (e. g., diameter) of 150 nm or less. In some embodiments, inventive nano­carriers have a greatest dimension (e. g., diameter) of 100 nm or less. In some embodiments, inventive nanocarriers have a greatest dimension ranging between 25 nm and 200 nm. In some embodiments, inventive nanocarriers have a greatest dimension ranging between 20 nm and 100 nm.

A variety of different nanocarriers can be used in accor­dance with the present invention. In some embodiments, nanocarriers are spheres or spheroids. In some embodi­ments, nanocarriers are flat or plate-shaped. In some embodiments, nanocarriers are cubes or cuboids. In some embodiments, nanocarriers are ovals or ellipses. In some embodiments, nanocarriers are cylinders, cones, or pyra­mids. Nanocarriers may be solid or hollow and may com­prise one or more layers. In some embodiments, each layer has a unique composition and unique properties relative to the other layer(s). To give but one example, nanocarriers may have a core/shell structure, wherein the core is one layer (e. g. a polymeric core) and the shell is a second layer (e. g. a lipid bilayer or monolayer). Nanocarriers may comprise a plurality of different layers. In some embodiments, one layer may be substantially cross-linked, a second layer is not substantially cross-linked, and so forth. In some embodi­ments, one, a few, or all of the different layers may comprise one or more immunomodulatory agents, targeting moieties, immuno stimulatory agents, and/or combinations thereof. In some embodiments, one layer comprises an immunomodu­latory agent, targeting moiety, and/or immuno stimulatory agent, a second layer does not comprise an immunomodu­latory agent, targeting moiety, and/or immuno stimulatory agent, and so forth. In some embodiments, each individual layer comprises a different immunomodulatory agent, tar­geting moiety, immuno stimulatory agent, and/or combina­tion thereof.

In some embodiments, nanocarriers may optionally com­prise one or more lipids. In some embodiments, a nanocar­

rier is a liposome. In some embodiments, a nanocarrier comprises a lipid bilayer. In some embodiments, a nanocar­rier comprises a lipid monolayer. In some embodiments, a nanocarrier is a micelle. In some embodiments, a nanocar­rier comprises a core of a polymeric matrix surrounded by a lipid layer (e. g. lipid bilayer, lipid monolayer, etc. ). In some embodiments, a nanocarrier comprises a non-poly- meric core (e. g. metal particle, quantum dot, ceramic par­ticle, bone particle, viral particle, etc. ) surrounded by a lipid layer (e. g. lipid bilayer, lipid monolayer, etc. ).

In some embodiments, a nanocarrier comprises one or more polymers. In some embodiments, a polymeric matrix can be surrounded by a coating layer (e. g. liposome, lipid monolayer, micelle, etc. ). In some embodiments, an immu­nomodulatory agent, targeting moiety, and/or immunostimu­latory agent can be associated with the polymeric matrix. In such embodiments, the immunomodulatory agent, targeting moiety, and/or immunostimulatory agent is effectively encapsulated within the nanocarrier.

In some embodiments, an immunomodulatory agent, tar­geting moiety, and/or immunostimulatory agent can be covalently associated with a nanocarrier. In some embodi­ments, covalent association is mediated by a linker. In some embodiments, an immunomodulatory agent, targeting moi­ety, and/or immuno stimulatory agent is non-covalently asso­ciated with a nanocarrier. For example, in some embodi­ments, an immunomodulatory agent, targeting moiety, and/ or immunostimulatory agent is encapsulated within, surrounded by, and/or dispersed throughout a polymeric matrix, a lipid membrane, etc. Alternatively or additionally, an immunomodulatory agent, targeting moiety, and/or immuno stimulatory agent may be associated with a poly­meric matrix, a lipid membrane, etc. by hydrophobic inter­actions, charge interactions, van der Waals forces, etc.

A wide variety of polymers and methods for forming polymeric matrices therefrom are known in the art of drug delivery. In general, a polymeric matrix comprises one or more polymers. Any polymer may be used in accordance with the present invention. Polymers may be natural or unnatural (synthetic) polymers. Polymers may be homopo­lymers or copolymers comprising two or more monomers. In terms of sequence, copolymers may be random, block, or comprise a combination of random and block sequences. Polymers in accordance with the present invention may be organic polymers. In some embodiments, the polymers are dendritic polymers or blends of polymers.

Examples of polymers include polyethylenes, polycar­bonates (e. g. poly(l, 3-dioxan-2one)), polyanhydrides (e. g. poly(sebacic anhydride)), polyhydroxyacids (e. g. poly(|> - hydroxy alkanoate)), polypropylfumerates, polycaprolac­tones, polyamides (e. g. polycaprolactam), polyacetals, polyethers, polyesters (e. g. polylactide, polyglycolide), poly (orthoesters), polycyanoacrylates, polyvinyl alcohols, poly­urethanes, polyphosphazenes, polyacrylates, polymethacry­lates, polyureas, polystyrenes, and polyamines.

In some embodiments, nanocarriers comprise immuno­modulatory agents embedded within reverse micelles. To give but one example, a liposome nanocarrier may comprise hydrophobic immunomodulatory agents embedded within the liposome membrane, and hydrophilic immunomodula­tory agents embedded with reverse micelles found in the interior of the liposomal nanocarrier.

In some embodiments, a nanocarrier does not include a polymeric component. In some embodiments, nanocarriers comprise metal particles, quantum dots, ceramic particles, bone particles, viral particles, etc. In some embodiments, an immunomodulatory agent, targeting moiety, and/or immu­

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nostimulatory agent is associated with the surface of such a non-polymeric nanocarrier. In some embodiments, a non- polymeric nanocarrier is an aggregate of non-polymeric components, such as an aggregate of metal atoms (e. g. gold atoms). In some embodiments, an immunomodulatory agent, targeting moiety, and/or immunostimulatory agent is associated with the surface of, encapsulated within, sur­rounded by, and/or dispersed throughout an aggregate of non-polymeric components.

In some embodiments, nanocarriers may optionally com­prise one or more amphiphilic entities (i. e., entities that possess both hydrophilic and hydrophobic properties). In some embodiments, an amphiphilic entity can promote the production of nanocarriers with increased stability, improved uniformity, or increased viscosity.

In some embodiments, a nanocarrier comprises one or more nanoparticles associated with the exterior surface of and/or encapsulated within the nanocarrier.

Nanocarriers may be prepared using any method known in the art. For example, particulate nanocarrier formulations can be formed by methods such as nanoprecipitation, flow focusing using fluidic channels, spray drying, single and double emulsion solvent evaporation, solvent extraction, phase separation, milling, microemulsion procedures, microfabrication, nanofabrication, sacrificial layers, simple and complex coacervation, as well as other methods well known to those of ordinary skill in the art. Alternatively or additionally, aqueous and organic solvent syntheses for monodisperse semiconductor, conductive, magnetic, organic, and other nanoparticles may be utilized.

In some embodiments, immunomodulatory agents, target­ing moieties, and/or immuno stimulatory agents, are not covalently associated with a nanocarrier. For example, nano­carriers may comprise a polymeric matrix, and immuno­modulatory agents, targeting moieties, and/or immunos­timulatory agents, etc. are associated with the surface of, encapsulated within, and/or distributed throughout the poly­meric matrix of an inventive nanocarrier. Immunomodula­tory agents may be released by diffusion, degradation of the nanocarrier, and/or a combination thereof. In some embodi­ments, polymer(s) of the nanocarrier degrade by bulk ero­sion. In some embodiments, polymer(s) of the nanocarrier degrade by surface erosion.

In some embodiments, immunomodulatory agents, target­ing moieties, and/or immunostimulatory agents are cova­lently associated with a particle. In some embodiments, covalent association is mediated by one or more linkers. Any suitable linker can be used in accordance with the present invention. In some embodiments, the linker is a cleavable linker (e. g., an ester linkage, an amide linkage, a disulfide linkage, etc. ).

In some embodiments, nanocarriers are made by self­assembly. As an example, lipids are mixed with a lipophilic immunomodulatory agent, and then formed into thin films on a solid surface. A hydrophilic immunomodulatory agent is dissolved in an aqueous solution, which is added to the lipid films to hydrolyze lipids under vortex. Liposomes with lipophilic immunomodulatory agents incorporated into the bilayer wall and hydrophilic immunomodulatory agents inside the liposome lumen are spontaneously assembled. In certain embodiments, pre-formulated polymeric nanopar­ticles are mixed with small liposomes under gentle vortex to induce liposome fusion onto polymeric nanoparticle surface.

As another example, a hydrophilic immunomodulatory agent to be encapsulated is first incorporated into reverse micelles by mixing with naturally derived and non-toxic amphiphilic entities in a volatile, water-miscible organic

solvent. In some embodiments, a biodegradable polymer is added after reverse micelle formation is complete. The resulting biodegradable polymer-reverse micelle mixture is combined with a polymer-insoluble hydrophilic non-solvent to form nanoparticles by the rapid diffusion of the solvent into the non-solvent and evaporation of the organic solvent.

In some embodiments, lipid monolayer stabilized poly­meric nanocarriers are used to deliver one or a plurality of immunomodulatory agents. In certain embodiments, a hydrophilic immunomodulatory molecule is first chemically conjugated to the polar headgroup of a lipid. The conjugate is mixed with a certain ratio of unconjugated lipid molecules in an aqueous solution containing one or more water- miscible solvents. A biodegradable polymeric material is mixed with the hydrophobic immunomodulatory agents to be encapsulated in a water miscible or partially water miscible organic solvent. The resulting polymer solution is added to the aqueous solution of conjugated and unconju­gated lipid to yield nanoparticles by the rapid diffusion of the organic solvent into the water and evaporation of the organic solvent.

The compositions and methods described herein can be used for the prophylaxis and/or treatment of any infectious disease, disorder, and/or condition. Examples of other dis­eases, disorders, and/or conditions are provided elsewhere herein. In some embodiments, vaccine nanocarriers in accor­dance with the present invention may be used to treat, alleviate, ameliorate, relieve, delay onset of, inhibit progres­sion of, reduce severity of, and/or reduce incidence of one or more symptoms or features of a disease, disorder, and/or condition. In some embodiments, inventive vaccine nano­carriers may be used to treat, alleviate, ameliorate, relieve, delay onset of, inhibit progression of, reduce severity of, and/or reduce incidence of one or more symptoms or fea­tures of microbial infection (e. g. bacterial infection, fungal infection, viral infection, parasitic infection, etc. ). In some embodiments, the prophylaxis and/or treatment of microbial infection comprises administering a therapeutically effective amount of inventive vaccine nanocarriers to a subject in need thereof, in such amounts and for such time as is necessary to achieve the desired result. In certain embodi­ments of the present invention, a “therapeutically effective amount” of an inventive vaccine nanocarrier is that amount effective for treating, alleviating, ameliorating, relieving, delaying onset of, inhibiting progression of, reducing sever­ity of, and/or reducing incidence of one or more symptoms or features of disease, disorder, and/or condition provided herein.

In some embodiments, inventive prophylactic and/or therapeutic protocols involve administering a therapeuti­cally effective amount of one or more inventive vaccine nanocarriers to a subject such that an immune response is modulated (e. g., stimulated in both T cells and/or В cells).

The present invention provides novel compositions com­prising a therapeutically effective amount of one or more vaccine nanocarriers and one or more pharmaceutically acceptable excipients. In some embodiments, the present invention provides for pharmaceutical compositions com­prising inventive vaccine nanocarriers as described herein. The composition may include more than one type of nano­carrier, each type having different constituents (e. g., immu­nomodulatory agents, targeting agents, immuno stimulatory agents, excipients, etc. ). In accordance with some embodi­ments, a method of administering a pharmaceutical compo­sition comprising inventive compositions to a subject (e. g. human) in need thereof is provided.

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