Abstract: In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.

Abstract: In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.

Abstract: The invention relates to immunogenic compositions for inducing an immune response to HIV comprising combinations of two, three, or four plasmids, where each plasmid is expressing a defined antigen, which may be a single antigen or a fusion of two or three antigens.

Abstract: In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.

Abstract: In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.

Abstract: In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.

Abstract: In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.

Abstract: The invention relates to immunogenic compositions for inducing an immune response to HIV comprising combinations of two, three, or four plasmids, where each plasmid is expressing a defined antigen, which may be a single antigen or a fusion of two or three antigens.

Abstract: A method of producing propagation-defective Vesicular Stomatitis Virus (VSV) in a cell culture is provided. The method involves introducing a plasmid vector encoding an optimized VSV G gene into a cell; expressing VSV G protein from the optimized VSV G gene; and introducing a propagation-defective VSV into the cell expressing the VSV G protein encoded by the optimized VSV G gene. The method further includes growing the cells in culture; and recovering the propagation-defective VSV from the culture.

Abstract: A method of producing propagation-defective Vesicular Stomatitis Virus (VSV) is provided. The method involves providing a cell that includes an optimized VSV G gene, wherein expression of VSV G protein from the optimized VSV G gene is inducible; and inducing the cell to express VSV G protein from the optimized VSV G gene. The method also involves infecting the induced cell with an attenuated VSV; growing the infected cells in culture; and recovering attenuated VSV from the culture.

Abstract: Modified polynucleotide compositions providing enhanced gene expression and methods for preparing said compositions are disclosed. Methods of using the compositions, such as in screening assays, diagnostic tools, kits, etc. and for prevention and/or treatment of diseases and disorders are also disclosed.

Abstract: A method for inducing and enhancing protective and/or therapeutic immunity in a mammal to HSV includes the steps of at least one immunization with an effective amount of a DNA vaccine composition which comprises a first nucleic acid molecule comprising a DNA sequence encoding the HSV type 1 or type 2 gD protein, and a second nucleic acid molecule comprising a DNA sequence encoding each Interleukin-12 heterodimer subunit. The method also comprises at least one subsequent immunization with an effective amount of a protein vaccine composition which comprises the HSV type 1 or type 2 gD protein; and the IL-12 heterodimer. A local anesthetic may be included in the DNA vaccine composition in an amount that forms one or more complexes with the nucleic acid molecules. When provided to the mammal in suitable effective dosages according to this protocol, the vaccine compositions used in this method produce an unexpectedly good protective and/or therapeutic immune response against HSV in an immunized mammal.

Abstract: A method for inducing and enhancing protective and/or therapeutic immunity in a mammal to HSV includes the steps of at least one immunization with an effective amount of a DNA vaccine composition which comprises a first nucleic acid molecule comprising a DNA sequence encoding the HSV type 1 or type 2 gD protein, and a second nucleic acid molecule comprising a DNA sequence encoding each Interleukin-12 heterodimer subunit. The method also comprises at least one subsequent immunization with an effective amount of a protein vaccine composition which comprises the HSV type 1 or type 2 gD protein; and the IL-12 heterodimer. A local anesthetic may be included in the DNA vaccine composition in an amount that forms one or more complexes with the nucleic acid molecules. When provided to the mammal in suitable effective dosages according to this protocol, the vaccine compositions used in this method produce an unexpectedly good protective and/or therapeutic immune response against HSV in an immunized mammal.