Abstract: The present invention relates to isolated or purified asporogenous Bacillus megaterium (B. megaterium) strains comprising a B. megaterium genome, wherein said genome is modified in that the spo0A gene is deleted or functionally deleted and the strain does not produce spores. The aspororogenous strains of the invention may be further modified by a deletion or functional deletion of one or more genes selected from xylA, xylR, leuC and leuD. The strains of the invention may further comprise an expression vector, wherein the expression vector comprises a sequence of nucleotides that encodes a heterologous polypeptide, operatively liked to a promoter. Also provided by the invention are modified expression vectors and promoters for use in the B. megaterium expression systems of the invention and methods of use thereof.

Abstract: The present invention relates to recombinant C. difficile toxin A (TcdA) and toxin B (TcdB) and binary toxin A (CDTa) proteins comprising specifically defined mutations relative to the native toxin sequence that substantially reduce or eliminate toxicity. The invention also relates to vaccines and immunogenic compositions comprising these recombinant toxins, as well as combinations of these toxins with binary toxin B (CDTb), which are capable of providing protection against C. difficile infection and/or the effects thereof. The invention also relates to methods of inducing an immune response to C. difficile comprising administering the vaccines and immunogenic compositions described herein to a patient. The invention also encompasses methods of expressing recombinant C. difficile toxin A and toxin B and CDTa mutants and CDTb in recombinant expression systems.

Abstract: The present invention relates to recombinant C. difficile toxin A (TcdA) and toxin B (TcdB) and binary toxin A (CDTa) proteins comprising specifically defined mutations relative to the native toxin sequence that substantially reduce or eliminate toxicity. The invention also relates to vaccines and immunogenic compositions comprising these recombinant toxins, as well as combinations of these toxins with binary toxin B (CDTb), which are capable of providing protection against C. difficile infection and/or the effects thereof. The invention also relates to methods of inducing an immune response to C. difficile comprising administering the vaccines and immunogenic compositions described herein to a patient. The invention also encompasses methods of expressing recombinant C. difficile toxin A and toxin B and CDTa mutants and CDTb in recombinant expression systems.

Abstract: The invention relates to nucleic acid molecules that include at least one death effector domain, expression vectors the include these nucleic acid molecules, host cells transformed with such vectors, methods for expressing and/or isolating gene products with at least one death effector domain, and purified or isolated gene products or fragments of these gene products that include at least one death effector domain.