Abstract: Fusion proteins include full-length flagellin or portions of flagellin fused to at least one Clostridium difficile antigen. Fusion proteins can include a first Clostridium difficile antigen that replaces at least a portion or the entirety of domain 3 of flagellin and a second Clostridium difficile antigen fused to the carboxy terminal amino acid of flagellin. Fusion proteins can also include at least one Clostridium difficile antigen fused to the most carboxy terminus of portions of flagellin or full length flagellin. Methods that employ fusion proteins are administered to humans to ameliorate Clostridium difficile associated disease.

Abstract: Compositions that include at least three fusion proteins comprising flagellin and influenza antigens. In embodiments, the influenza antigens can include influenza A and influenza B antigens. The composition can further include at least one adjuvant.

Abstract: Compositions that include a fusion protein comprising flagellin and at least one antigen that has an isoelectric point greater than about 7.0 and that is fused to at least one domain 3 of the flagellin activate Toll-like Receptor 5. Methods of stimulating an immune response, in particular, a protective immune response include administering a composition that includes an antigen fused to a loop of domain 3 of flagellin.

Abstract: Compositions that include a fusion protein comprising flagellin and at least one antigen that has an isoelectric point greater than about 7.0 and that is fused to at least one domain 3 of the flagellin activate Toll-like Receptor 5. Methods of stimulating an immune response, in particular, a protective immune response include administering a composition that includes an antigen fused to a loop of domain 3 of flagellin.

Abstract: The present invention relates to improved vaccines and the design and making of such vaccines that enhance immunogenicity of the vaccine and/or reduce reactogenicity to the vaccine when administered. In particular the vaccines and immunogenic compositions of the present invention relate to flagellin-antigen fusion proteins in which the spatial orientation of the flagellin to antigen and the charge distribution of the antigen is optimized to enhance immunogenicity and/or reduce reactogenicity and/or improve folding of the protein.

Abstract: Compositions that include a fusion protein comprising flagellin and at least one antigen that has an isoelectric point greater than about 7.0 and that is fused to at least one domain 3 of the flagellin activate Toll-like Receptor 5. Methods of stimulating an immune response, in particular, a protective immune response include administering a composition that includes an antigen fused to a loop of domain 3 of flagellin.

Abstract: The present invention relates to improved vaccines and the design and making of such vaccines that enhance immunogenicity of the vaccine and/or reduce reactogenicity to the vaccine when administered. In particular the vaccines and immunogenic compositions of the present invention relate to flagellin-antigen fusion proteins in which the spatial orientation of the flagellin to antigen and the charge distribution of the antigen is optimized to enhance immunogenicity and/or reduce reactogenicity. The present invention also relates to methods of evaluating the vaccines by measuring the relative expression of certain gene markers. Altered expression of the genes relative to flagellin control sample may indicate that the vaccine is suitable to stimulate an adaptive immune response to the antigen component in the subject with minimal side effects.

Abstract: Polynucleotides encoding at least one immunizing antigen whose expression is controlled by a promoter derived from a gene encoding a co-stimulatory molecule are provided. The polynucleotides may also encode adjuvants. Compositions comprising at least one immunizing agent and at least one cytokine that enhance dendritic cell stimulation and/or survival are also provided. Methods for eliciting an immune response against the immunizing agent are also provided. The method includes the steps of administering the polynucleotides and, optionally, co-administering an adjuvant.

Abstract: Polynucleotides encoding at least one immunizing antigen whose expression is controlled by a promoter derived from a gene encoding a co-stimulatory molecule are provided. The polynucleotides may also encode adjuvants. Compositions comprising at least one immunizing agent and at least one cytokine that enhance dendritic cell stimulation and/or survival are also provided. Methods for eliciting an immune response against the immunizing agent are also provided. The method includes the steps of administering the polynucleotides and, optionally, co-administering an adjuvant.

Abstract: Polynucleotides encoding at least one immunizing antigen whose expression is controlled by a promoter derived from a gene encoding a co-stimulatory molecule are provided. The polynucleotides may also encode adjuvants. Compositions comprising at least one immunizing agent and at least one cytokine that enhance dendritic cell stimulation and/or survival are also provided. Methods for eliciting an immune response against the immunizing agent are also provided. The method includes the steps of administering the polynucleotides and, optionally, co-administering an adjuvant.