Abstract: 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.

Abstract: 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. In certain embodiments of the invention the agents include at least one curcuminoid.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The present invention provides techniques and reagents that induce an immune response against tumor cells. According to the invention, tumor cell components are contacted with a sensitizing agent, preferably so that one or more tumor cell components become haptenized with a sensitizing agent, and the resulting combination is administered to a patient suffering from a tumor, so that an anti-tumor immune response is mounted. In some embodiments of the invention, sensitizing agent/tumor cell component compositions are administered directly to a patient; in other embodiments they are administered by means of an antigen presenting cell such as a dendritic cell.

Abstract: Methods and pharmaceutical compositions for preventing and treating disease mediated by toxin-secreting bacteria. Inventive methods and compositions are suited to preventing or treating infections caused by bacterial toxins that enter host cells via receptor-mediated endocytosis (e.g., the anthrax and diphtheria toxins). Methods comprise a step of administering to an individual a pharmaceutical composition that includes an effective amount of an inhibitor of endosomal acidification. The inhibitor may be a primary amine, a carboxylic ionophore, or a selective inhibitor of the vacuolar proton pump (V-ATPase). The inhibitors of endosomal acidification may be employed in combination with other therapeutics such as antibiotics and antitoxins in order to prevent, treat or cure the disease.

Abstract: 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.

Abstract: It has been determined that allergens, which are characterized by both humoral (IgE) and cellular (T-cell) binding sites, can be modified to be less allergenic by modifying the IgE binding sites. The IgE binding sites can be converted to non-IgE binding sites by altering as little as a single amino acid within the protein, preferably a hydrophobic residue towards the center of the IgE epitope, to eliminate IgE binding. Additionally or alternatively a modified allergen with reduced IgE binding may be prepared by disrupting one or more of the disulfide bonds that are present in the natural allergen. The disulfide bonds may be disrupted chemically, e.g., by reduction and alkylation or by mutating one or more cysteine residues present in the primary amino acid sequence of the natural allergen. In certain embodiments, modified allergens are prepared by both altering one or more linear IgE eitopes and disrupting one or more disulfide bonds of the natural allergen.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Compositions are administered to block IgE binding to receptors and ultimately displace native IgE from mast cells and related cell types, to prevent the activation of these cells during an allergic response. The compositions consist of a pharmaceutically acceptable carrier for systemic or local administration and an amount of compound binding specifically to the Fc&egr;RI IgE binding sites, and more preferably, Fc&egr;RI and Fc&egr;RII IgE binding sites, to prevent activation and degranulation of mast cells in response to exposure to allergens. The compounds can consist of IgE molecules and fragments and modifications thereof, such as IgE fragments, humanized or single chain IgE antibodies or fragments thereof, IgE with a modified Fab, non-crosslinkable IgE, or peptidomimetics which bind to the same site on the receptor as the IgE, jointly referred to herein as “IgE fragments” unless otherwise stated.

Abstract: IgE-blocking agents and methods of their use have been developed for desensitizing an individual to an antigen. These IgE-blocking agents work by blocking the antigen-binding site of the IgE molecules and thereby preventing the antigen from binding. These agents typically have up to one IgE binding site present per molecule so as prevent any cross-linking of IgE which could lead to an allergic reaction. Methods of using these novel IgE blocking agents include administering the agents to alleviate or prevent allergic reactions as well as administering the agents to decrease the risk of allergic reactions during immunotherapy or “rush” immunotherapy. Compositions and kits comprising these IgE binding agents are also provided.

Abstract: 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 particuarly 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.