Yeast-based immunotherapy against clostridium difficile infection
AssigneeUniversity of Maryland, Baltimore
InventorsHanping Feng, James Eugene GALEN, Kevin CHEN, Yixuan ZHU
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Abstract
Antibody-based binding agents derived from human and camelid immunoglobulins are described, as well as strains of yeast engineered to secrete the binding agents, and methods of treating and preventing Clostridium difficile infections using the engineered strains of yeast. 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. The binding agents include camelid VHH peptide monomers, linked groups of VHH peptide monomers, VHH peptide monomers joined to antibody Fc domains, and VHH peptide monomers joined to IgG antibodies.
Claims21
1-67. (canceled)
A method of preventing a primary Clostridum difficile (C. difficile) infection or preventing a recurrent C. difficile) infection in a subject, comprising administering an effective amount of an engineered strain of Saccharomyces boulardii yeast to the subject, wherein the engineered strain of Saccharomyces boulardii yeast produces a tetra-specific, tetrameric binding agent comprising:
- a first, a second, a third, and a fourth linked VHH peptide monomer, wherein the first and third VHH peptide monomers have binding specificity for epitopes of TcdA and comprise the amino acid sequences of AH3 (SEQ ID NO:7) and AA6 (SEQ ID NO:5), respectively, and wherein the second and fourth VHH peptide monomers have binding specificity for epitopes of TcdB and comprise the amino acid sequences 5D (SEQ ID NO:1) and E3 (SEQ ID NO:
- 3), respectively.
A method of reducing recurrence of a Clostridum difficile (C. difficile) infection in a subject, comprising administering an engineered strain of Saccharomyces boulardii yeast that produces a VHH peptide binding agent comprising a first, second, third, and fourth VHH peptide monomer, wherein each VHH peptide monomer independently has binding specificity for a unique epitope of Clostridium difficile toxin A (TcdA) or toxin B (TcdB).
A method of treating a Clostridum difficile (C. difficile) infection in a subject, comprising administering an engineered strain of Saccharomyces boulardii yeast that produces a VHH peptide binding agent comprising a first, second, third, and fourth VHH peptide monomer, wherein each VHH peptide monomer independently has binding specificity for a unique epitope of Clostridium difficile toxin A (TcdA) or toxin B (TcdB).
Dependencies are inferred from the claim text.