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: The present invention relates to immunogenic compositions and vaccines of flavivirus. In particular, the present invention relates to improved Dengue vaccines and the design and making of such vaccines that enhance immunogenicity of the vaccine. The vaccines and immunogenic compositions of the present invention relate to mixed head bivalent flagellin-dengue antigen fusion proteins which can be combined with other bivalent dengue antigen fusion proteins or monovalent dengue antigen fusion proteins to produce multivalent vaccine including tetravalent vaccines.

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: Compositions that include a flagellin/antigen protein comprising at least a portion of at least one flagellin and at least a portion of at least one antigen and methods of administering these compositions to humans at least 49 years old. The compositions stimulate immune response to the antigen, in particular, a protective immune response to the antigen, in the human, such as an elderly human.

Abstract: Methods of making and compositions that stimulate a protective immune response in a subject include a portion of a protein from a naturally occurring viral hemagglutinin, wherein the protein portion includes at least a portion of a globular head and at least a portion of at least one secondary structure that causes the globular head to essentially retain its tertiary structure, and wherein the protein portion lacks a membrane fusion domain, a transmembrane domain and a cytoplasmic domain. Compositions can further include a Toll-like Receptor agonist and a carrier protein.