Abstract: A bifunctional composition comprising an intracellularly effective immunomodulating nucleic acid component containing at least one immunostimulatory, immunoinhibitory or immunomodulating motif and selected from a mononucleotide, a dinucleotide, an oligonucleotide or a polynucleotide with either a natural phosphodiester backbone or a modified backbone, optionally in combination with a specific antigen, in association with a protein binding to specific receptors on mammalian cell surfaces selected from the group consisting of cholera toxin (CT), the subunit B of CT (CTB), Escherichia coli heat labile enterotoxin (LT), the subunit B of LT (LTB), and proteins or protein derivatives that react with antiserum to CT or LT, bind to GM1 ganglioside, ADP-ribosylates an acceptor protein, or give rise to accumulation of cyclic AMP in target cells, and antibodies or other proteins which after binding to a specific cell surface component can be internalized into the cell, is described.
Abstract: Described are methods for inducing both a mucosal and a systemic immune response in the respiratory, digestive or urogenital tracts of a mammal to a microbial pathogen. The methods comprise topically administering onto the sublingual mucosa of the mammal an amount of an antigen effective to induce the mucosal and systemic immune responses and a pharmaceutically acceptable carrier or diluent. Pharmaceutical formulations and dosage forms for immunizing a mammal against a microbial pathogen to elicit a mucosal and systemic immune response in the respiratory, digestive or urogenital tracts are also described.
Abstract: The present invention discloses the use of the non-toxic cell-binding B subunit of CT (CTB), and holotoxin CT that is devoid of ADP-ribosylating activity, as adjuvants for enhancing transcutaneous immune response to a co-administered protein allergen. It was found that topical administration of CTB to mice induced serum antibody response against itself comparable to those evoked by CT, but was inefficient at promoting systemic antibody responses against an admixed prototype protein allergen. To the contrary co-administration of either CT or CTB with allergen led to vigorous antigen-specific T cell proliferative responses in lymph nodes draining the cutaneous site of administration and at distant systemic sites. Consistent with these observations, it was found that CTB selectively potentiated Th1-driven responses without affecting Th2-dependent responses.
Abstract: An immunological tolerance-inducing agent comprising a mucosa-binding molecule linked to a specific tolerogen is disclosed. Further, a method of inducing immunological tolerance in an individual against a specific antigen, including hapten, which causes an unwanted immune response in said individual comprising administration by a mucosal route of an immunologically effective amount of an immunological tolerance-inducing agent of the invention to said individual, is described.
Abstract: An agent comprising a mucosa-binding molecule linked to a specific microbial antigen is disclosed. Further, a method of inducing immunological tolerance in an individual against a specific microbial antigen, including hapten, which causes an unwanted immune response in said individual, comprising administration by a mucosal route of an immunologically effective amount of an immunological tolerance-inducing agent of the invention to said individual, is described.
Abstract: An immunological tolerance-inducing agent comprising a mucosa-binding molecule linked to a specific tolerogen is disclosed. Further, a method of inducing immunological tolerance in an individual against a specific antigen, including hapten, which causes an unwanted immune response in said individual comprising administration by a mucosal route of an immunologically effective amount of an immunological tolerance-inducing agent of the invention to said individual, is described.