The present invention relates to the use of a composition selected from the group consisting of antibodies, antibody fragments, insulin-like growth factor antagonists, Toll-like receptor antagonists and mixtures thereof for the treatment or the prophylaxis of certain diseases.

Novel, antibody-based binding agents derived from camelid V.sub.HH and human immunoglobulins are described. These binding agents recognize and bind with specificity to Clostridium difficile toxin A and/or toxin B and in some cases exhibit toxin neutralizing activity. These binding agents can be used to treat or prevent primary and recurrent CDI. The binding agents include humanized V.sub.HH peptide monomers, linked groups of humanized V.sub.HH peptide monomers, humanized V.sub.HH peptide monomers joined to antibody Fc domains, and humanized V.sub.HH peptide monomers joined to IgG antibodies.

In an embodiment, the present disclosure pertains to a method of treating or preventing C. difficile infections. In some embodiments, the method includes administering an antitoxin to a subject in need thereof. In some embodiments, the antitoxin includes a designed ankyrin repeat protein (DARPin). In an additional embodiments, the present disclosure pertains to a composition including an antitoxin for treating or preventing C. difficile infections. In some embodiments, the anti-toxin includes a DARPin. In some embodiments, the anti-toxin is a monomeric or dimeric DARPin for the neutralization of Clostridium difficile toxin B (TcdB).

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.

Compositions and methods of the present invention prevent, inhibit or reduce the toxic effects of proteins and toxins secreted from microbes. A method for neutralizing microbial protein products in a subject comprises administering a composition to the subject, said composition comprising plasma-derived IgM and optionally one or more excipients in a pharmaceutical carrier, wherein the composition is administered in an amount effective to neutralize the microbial protein products.

This present invention provides C-TAB.G5 and C-TAB.G5.1 isolated polypeptides comprising the receptor binding domains of C. difficile toxin A and toxin B as set forth in the amino acid sequences of SEQ ID NO: 2 and SEQ ID NO: 4. The C-TAB.G5 and C-TAB.G5.1 isolated polypeptides may be used to neutralize toxic effects of C. difficile toxin A and/or toxin B.

A VAMP epitope suitable for generating an antibody against a VAMP C-terminal neurotoxin cleavage product. Method of using such an epitope to generate an antibody against cleaved VAMP. Method of using such an antibody to assay for cleavage of a VAMP by clostridial neurotoxin.

The present application relates to recombinant Clostridium difficile antigens based on a fusion protein that consists of or comprises a first amino acid sequence and a second amino acid sequence, wherein: a) the first amino acid sequence is provided by an amino acid sequence that has at least 80% sequence identity with an amino acid sequence consisting of residues 1500-1850 of a C. difficile Toxin A sequence or residues 1500-1851 of a C. difficile Toxin B sequence; and b) the second amino acid sequence is provided by an amino acid sequence that has at least 80% sequence identity with an amino acid sequence consisting of a long repeat unit located within amino acid residues 1851-2710 of a C. difficile Toxin A sequence or within amino acid residues 1852-2366 of a C. difficile Toxin B sequence; though with the proviso that the fusion protein is not a polypeptide comprising amino acid residues 543-2710 of a C. difficile Toxin A and with the proviso that the fusion protein is not a polypeptide comprising amino acid residues 543-2366 of a C. difficile Toxin B. Also provided is the use of said antigens for the prevention/treatment/suppression of Clostridium difficile infection (CDI), together with methods for generating said antigens, methods for generating antibodies that bind to said antigens, and the use of said antibodies for the prevention/treatment/suppression of CDI.

This present invention provides C-TAB.G5 and C-TAB.G5.1 isolated polypeptides comprising the receptor binding domains of C. difficile toxin A and toxin B as set forth in the amino acid sequences of SEQ ID NO: 2 and SEQ ID NO: 4. The C-TAB.G5 and C-TAB.G5.1 isolated polypeptides may be used to neutralize toxic effects of C. difficile toxin A and/or toxin B.

A new cell line and an antibody for determining the activity of botulinum toxin are disclosed. Also disclosed is a method of determining the activity of botulinum toxin using the cell line and/or the antibody.