NANOPARTICLES FOR TREATMENT OF ALLERGY

The present invention encompasses the surprising finding that nanoparticle compositions can have beneficial effects on allergy even when prepared without a known specific allergy therapeutic. The present invention provides such nanoparticle compositions. In some embodiments, provided nanoparticles are associated with functional elements that cause the nanoparticles to mimic bacterial cells. The present invention encompasses the surprising finding that provided nanoparticles may be useful for treatment and/or prevention of multiple different allergies in a single patient. The present invention encompasses the recognition that provided empty nanoparticles may be useful as a “pan-allergy” therapeutic and/or vaccine. 1. A composition comprising a population of nanoparticles , wherein the composition is substantially free of any allergy-specific antigen , and further wherein nanoparticles of the composition comprise at least one microbial mimic entity.2. The composition of claim 1 , wherein all of the particles within the population contain identical microbial mimic entities.3. The composition of or claim 1 , wherein the microbial mimic entity is selected from the group consisting of bacterial lipopolysaccharide (“LPS”) claim 1 , bacterial flagellin claim 1 , lipoteichoic acid from gram positive bacteria claim 1 , peptidoglycan claim 1 , double-stranded RNAs (“dsRNAs”) claim 1 , unmethylated CpG motifs claim 1 , characteristic portions thereof claim 1 , and combinations thereof.4. The composition of claim 1 , wherein the population contains at least two subpopulations of particles claim 1 , wherein all of the particles within each subpopulation contain identical microbial mimic entities.5. The composition of claim 4 , wherein the first subpopulation of particles comprises a first microbial mimic entity claim 4 , and the second subpopulation of particles comprises a second microbial mimic entity.6. The composition of claim 4 , wherein the first subpopulation of particles ...

Nanoparticles for treatment of allergy

The present invention encompasses the surprising finding that nanoparticle compositions can have beneficial effects on allergy even when prepared without a known specific allergy therapeutic. The present invention provides such nanoparticle compositions. In some embodiments, provided nanoparticles are associated with functional elements that cause the nanoparticles to mimic bacterial cells. The present invention encompasses the surprising finding that provided nanoparticles may be useful for treatment and/or prevention of multiple different allergies in a single patient. The present invention encompasses the recognition that provided empty nanoparticles may be useful as a “pan-allergy” therapeutic and/or vaccine.

Microbial delivery system

The present invention provides methods and compositions for treating or preventing allergic responses, particularly anaphylactic allergic responses, in subjects who are allergic to allergens or susceptible to allergies. Methods of the present invention utilize administration of microorganisms to subjects, where the microorganisms produce allergens and protect the subjects from exposure to the allergens until phagocytosed by antigen-presenting cells. Particularly preferred microorganisms are gram-negative bacteria, gram-positive bacteria, and yeast. Particularly preferred allergens are proteins found in foods, venoms, drugs and latex that elicit allergic reactions and anaphylactic allergic reactions in individuals who are allergic to the proteins or are susceptible to allergies to the proteins. The proteins may also be modified to reduce the ability of the proteins to bind and crosslink IgE antibodies and thereby reduce the risk of eliciting anaphylaxis without affecting T-cell mediated Th1-type immunity.

Microbial delivery system

The present invention provides methods and compositions for treating or preventing allergic responses, particularly anaphylactic allergic responses, in subjects who are allergic to allergens or susceptible to allergies. Methods of the present invention utilize administration of microorganisms to subjects, where the microorganisms produce allergens and protect the subjects from exposure to the allergens until phagocytosed by antigen-presenting cells. Particularly preferred microorganisms are gram-negative bacteria, gram-positive bacteria, and yeast. Particularly preferred allergens are proteins found in foods, venoms, drugs and latex that elicit allergic reactions and anaphylactic allergic reactions in individuals who are allergic to the proteins or are susceptible to allergies to the proteins. The proteins may also be modified to reduce the ability of the proteins to bind and crosslink IgE antibodies and thereby reduce the risk of eliciting anaphylaxis without affecting T-cell mediated Th1-type immunity.

IMMUNE MODULATION

The disclosure relates to compositions, methods of use and making, and kits for immunomodulation. In some embodiments, the present invention also provides compositions including at least one antigen substantially co-localized with at least one adjuvant agent in a format selected from patch, capsule, tablet, gel, matrix, paste, reservoir, adhesive, liquid, suspension, lyophilized solid, liquid contained within one or more lumenal units, and combinations thereof, wherein one or both of the antigen and the adjuvant agent is a crude preparation, and wherein the composition is characterized in that administration to a subject in need thereof results in an immune response in the subject to the antigen. 1. A composition comprising:at least one antigen substantially co-localized with at least one adjuvant agent in a format selected from patch, capsule, tablet, gel, matrix, paste, reservoir, adhesive, liquid, suspension, lyophilized solid, liquid contained within one or more lumenal units, and combinations thereof, wherein one or both of the antigen and the adjuvant agent is a crude preparation, and wherein the composition is characterized in that administration to a subject in need thereof results in an immune response in the subject to the antigen.2. The composition of claim 1 , wherein the antigen is a Th2 associated antigen and the immune response is not a predominantly Th2 response.3. The composition of claim 1 , wherein the antigen is a Th1 associated antigen and the immune response is not a predominantly Th1 response.4. The composition of claim 1 , designed and constructed to deliver both the antigen and the adjuvant to a population of the subject's cells.5. The composition of claim 4 , wherein the population of the subject's cells is or comprises immune cells.6. The composition of claim 5 , wherein the immune cells are or comprise antigen presenting cells.7. The composition of claim 2 , wherein the immune response is a predominantly Th1 response.8. The composition of ...

Modular nanodevices for smart adaptable vaccines

Modular nanoparticle vaccine compositions and methods of making and using the same have been developed. Modular nanoparticle vaccine compositions comprise an antigen encapsulated in a polymeric particle and adaptor elements which modularly couple functional elements to the particle. The modular design of these vaccine compositions, which involves flexible addition and subtraction of antigen, adjuvant, immune potentiators, molecular recognition and transport mediation elements, as well as intracellular uptake mediators, allows for exquisite control over variables that are important in optimizing an effective vaccine delivery system.

MODULAR NANODEVICES FOR SMART ADAPTABLE VACCINES

Modular nanoparticle vaccine compositions and methods of making and using the same have been developed. Modular nanoparticle vaccine compositions comprise an antigen encapsulated in a polymeric particle and adaptor elements which modularly couple functional elements to the particle. The modular design of these vaccine compositions, which involves flexible addition and subtraction of antigen, adjuvant, immune potentiators, molecular recognition and transport mediation elements, as well as intracellular uptake mediators, allows for exquisite control over variables that are important in optimizing an effective vaccine delivery system. 125.-. (canceled)26. A composition comprisingone or more antigens encapsulated in or incorporated into a polymeric nanoparticle that is surface modified with an adjuvant that is a bacterial or microbial derivative.27. The composition of claim 26 , wherein the bacterial or microbial derivative is selected from the group consisting of carbohydrates claim 26 , immunostimulatory oligonucleotides claim 26 , ADP-ribosylating toxins or detoxified derivatives thereof claim 26 , and combinations thereof.28. The composition of claim 26 , further comprising at least one protective layer claim 26 , wherein the protective layer is one which decreases particle degradation relative to a particle without a protective layer upon administration to a subject in need thereof.29. The composition of claim 27 , wherein the carbohydrates are or comprise lipopolysaccharide (LPS).30. The composition of claim 26 , wherein the bacterial or microbial derivative is or comprises a cell wall component of a gram negative bacteria.31. The protective layer of claim 28 , which is or comprises one or more of an enteric coating claim 28 , a physically-protective layer claim 28 , an environmentally-sensitive coating claim 28 , and a pH-responsive coating.32. The composition of claim 26 , wherein the one or more antigens are selected from the group consisting of viral claim 26 ...

NANOPARTICLES FOR TREATMENT OF ALLERGY

The present invention encompasses the surprising finding that nanoparticle compositions can have beneficial effects on allergy even when prepared without a known specific allergy therapeutic. The present invention provides such nanoparticle compositions. In some embodiments, provided nanoparticles are associated with functional elements that cause the nanoparticles to mimic bacterial cells. The present invention encompasses the surprising finding that provided nanoparticles may be useful for treatment and/or prevention of multiple different allergies in a single patient. The present invention encompasses the recognition that provided empty nanoparticles may be useful as a “pan-allergy” therapeutic and/or vaccine. 1. A composition comprising a population of nanoparticles , wherein the composition is substantially free of any allergy-specific antigen , and further wherein nanoparticles of the composition comprise at least one microbial mimic entity.2. The composition of claim 1 , wherein all of the particles within the population contain identical microbial mimic entities.3. The composition of claim 2 , wherein the microbial mimic entity is selected from the group consisting of bacterial lipopolysaccharide (“LPS”) claim 2 , bacterial flagellin claim 2 , lipoteichoic acid from gram positive bacteria claim 2 , peptidoglycan claim 2 , double-stranded RNAs (“dsRNAs”) claim 2 , unmethylated CpG motifs claim 2 , characteristic portions thereof claim 2 , and combinations thereof.4. The composition of claim 1 , wherein the population contains at least two subpopulations of particles claim 1 , wherein all of the particles within each subpopulation contain identical microbial mimic entities.5. The composition of claim 4 , wherein the first subpopulation of particles comprises a first microbial mimic entity claim 4 , and the second subpopulation of particles comprises a second microbial mimic entity.6. The composition of claim 4 , wherein the first subpopulation of particles ...

NANOPARTICLES FOR TREATMENT OF ALLERGY

The present invention encompasses the surprising finding that nanoparticle compositions can have beneficial effects on allergy even when prepared without a known specific allergy therapeutic. The present invention provides such nanoparticle compositions. In some embodiments, provided nanoparticles are associated with functional elements that cause the nanoparticles to mimic bacterial cells. The present invention encompasses the surprising finding that provided nanoparticles may be useful for treatment and/or prevention of multiple different allergies in a single patient. The present invention encompasses the recognition that provided empty nanoparticles may be useful as a “pan-allergy” therapeutic and/or vaccine. 117-. (canceled)18. A method of characterizing a preparation comprising a population of PLGA nanoparticles , which nanoparticles are substantially free of one or more allergens , the method comprising steps of:(i) assessing size distribution of nanoparticles in the preparation;(ii) assessing ability to suppress Th2 and/or increase Th1-type immune responses.19. The method of claim 18 , wherein the surfaces of the nanoparticles are associated with one or more modifications.20. The method of claim 19 , wherein the one or more modifications is or comprises a microbial mimic entity.21. The method of claim 20 , wherein the microbial mimic entity is or comprises a PAMP.22. The method of claim 21 , wherein the PAMP is one or both of LPS and flagellin.23. The method of claim 22 , wherein if both LPS and flagellin are present claim 22 , the ratio of LPS to flagellin is 9:1.24. The method of claim 23 , wherein LPS and flagellin may be present on the same or different nanoparticles in the population.25. The method of claim 19 , wherein the nanoparticles further comprise CpG claim 19 , and wherein the CpG is optionally encapsulated within the nanoparticles.26. The method of claim 22 , wherein the nanoparticles further comprise CpG claim 22 , and wherein the CpG is ...

Nanoparticles for treatment of allergy

The present invention encompasses the surprising finding that nanoparticle compositions can have beneficial effects on allergy even when prepared without a known specific allergy therapeutic. The present invention provides such nanoparticle compositions. In some embodiments, provided nanoparticles are associated with functional elements that cause the nanoparticles to mimic bacterial cells. The present invention encompasses the surprising finding that provided nanoparticles may be useful for treatment and/or prevention of multiple different allergies in a single patient. The present invention encompasses the recognition that provided empty nanoparticles may be useful as a “pan-allergy” therapeutic and/or vaccine.

Nanoparticles for treatment of allergy

The present invention encompasses the surprising finding that nanoparticle compositions can have beneficial effects on allergy even when prepared without a known specific allergy therapeutic. The present invention provides such nanoparticle compositions. In some embodiments, provided nanoparticles are associated with functional elements that cause the nanoparticles to mimic bacterial cells. The present invention encompasses the surprising finding that provided nanoparticles may be useful for treatment and/or prevention of multiple different allergies in a single patient. The present invention encompasses the recognition that provided empty nanoparticles may be useful as a "pan-allergy" therapeutic and/or vaccine.

Conductance of improperly folded proteins through the secretory pathway and related methods for treating disease

This invention provides the methodology and agents for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention of proteins. Thus, the methods and agents of the present invention provide for the release of normally retained proteins from the endoplasmic reticulum. The present invention is particularly useful for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention or degradation of mis-assembled or mis-folded proteins.

Conductance of improperly folded proteins through the secretory pathway and related methods for treating disease

Compositions and methods for the treatment of autosomal dominant polycystic kidney disease and other diseases having upregulated mtor activity

PC1-CTT polypeptides for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) are provided and can be or include PC1-CTT (SEQ ID NO:1) or a functional fragment or variant thereof. In some embodiments, the PC1-CTT polypeptide is a fusion protein or conjugate further including a functional element such as a protein transduction domain, fusogenic polypeptide, targeting signal, or expression and/or purification tag. Nucleic acids encoding the disclosed PC1-CTT polypeptides and other therapeutic proteins are also provided. In some embodiments, the nucleic acid encodes a TOP or TOP-like motif. The nucleic acids can be RNA or DNA, and can be, for example, a vector such as a plasmid or viral vector, or an mRNA. Methods of treatment are provided and typically include administering a subject in need thereof an effective amount of a disclosed polypeptide or nucleic acid.

Conductance of improperly folded proteins through the secretory pathway and related methods for treating disease

This invention provides the methodology and agents for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention of proteins. Thus, the methods and agents of the present invention provide for the release of normally retained proteins from the endoplasmic reticulum. The present invention is particularly useful for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention or degradation of mis-assembled or mis-folded proteins.

Methods for skewing the balance between th1 and th2 immune responses

Methods for preventing or treating disease mediateb by toxin-secreting bacteria

Methods for skewing the balance between th1 and th2 immune responses

The present invention provides compositions and methods for regulating immune system reactions by biasing T cell responses away from Th1 or Th2 responses in a pre-determined manner. Control is effected at the stage of antigen/APC encounter and/or at the stage of APC/T cell encounter. In preferred embodiments, a Th1 or Th2 response is inhibited through induction of the alternative response. The inventive methods and reagents are particularly useful for the management of autoimmune disorders, allergy, and asthma.

Conductance of improperly folded proteins through the secretory pathway and related methods for treating disease

This invention provides the methodology and agents for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention of proteins. Thus, the methods and agents of the present invention provide for the release of normally retained proteins form the endoplasmic reticulum. The present invention is particularly useful for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention or degradation of mis-assembled or mis-folded proteins. In certain embodiments of the invention the agents include at least one curcuminoid.

Conductance of improperly folded proteins through the secretory pathway and related methods for treating disease

This invention provides the methodology and agents for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention of proteins. Thus, the methods and agents of the present invention provide for the release of normally retained proteins form the endoplasmic reticulum. The present invention is particularly useful for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention or degradation of mis-assembled or mis-folded proteins. In certain embodiments of the invention the agents include at least one curcuminoid.

Compositions and methods for the treatment of autosomal dominant polycystic kidney disease and other diseases having upregulated mtor activity

PC1-CTT polypeptides for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) are provided and can be or include PC1-CTT (SEQ ID NO:1) or a functional fragment or variant thereof. In some embodiments, the PC1-CTT polypeptide is a fusion protein or conjugate further including a functional element such as a protein transduction domain, fusogenic polypeptide, targeting signal, or expression and/or purification tag. Nucleic acids encoding the disclosed PC1-CTT polypeptides and other therapeutic proteins are also provided. In some embodiments, the nucleic acid encodes a TOP or TOP-like motif. The nucleic acids can be RNA or DNA, and can be, for example, a vector such as a plasmid or viral vector, or an mRNA. Methods of treatment are provided and typically include administering a subject in need thereof an effective amount of a disclosed polypeptide or nucleic acid.

Conductance of improperly folded proteins through the secretory pathway

Modular nanoparticles for adaptable vaccines

Modular nanoparticle vaccine compositions and methods of making and using the same have been developed. Modular nanoparticle vaccine compositions comprise an antigen encapsulated in a polymeric particle and adaptor elements which modularly couple functional elements to the particle. The modular design of these vaccine compositions, which involves flexible addition and subtraction of antigen, adjuvant, immune potentiators, molecular recognition and transport mediation elements, as well as intracellular uptake mediators, allows for exquisite control over variables that are important in optimizing an effective vaccine delivery system.

Conductance of improperly folded proteins through the secretory pathway

This invention provides the methodology and agents for treating disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention of proteins. Thus, the methods and agents of the present invention provide for the release of normally retained proteins from the endoplasmic reticulum. The present invention is particularly useful for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention or degradation of mis-assembled or mis-folded proteins. In particular, thapsigargin, cyclopiazonic acid, DBHQ or halothane can be used to allow the release of ΔF508CFTR or of a secretion-incompetent variant null (Hong Kong) of α1-antitrypsin, in order to treat cystic fibrosis or chronic obstructive pulmonary disease (pulmonary emphysema) respectively.

Nanoparticle compositions

The present invention provides, among other things, nanoparticle compositions including a plurality of nanoparticles, each of which is comprised of a biodegradable or biocompatible polymer arranged in a nanoparticle structure defining an internal lumen and an external surface and one or more of a preparation of hydrophilic cellular components and a preparation of hydrophobic cellular components. In some embodiments, the preparation of hydrophilic cellular components is encapsulated within the internal lumen and the preparation of hydrophobic cellular components is associated with the external surface. Various methods of making and using disclosed nanoparticle compositions are also provided.