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A Protein Microarray Assay for Serological Determination of Antigen-specific Antibody Responses Following Clostridium difficile Infection
Published on: June 15, 2018
Neutralization of Clostridium difficile toxin A using antibody combinations.
Stephen J Demarest1, Mangala Hariharan, Marikka Elia
1Verenium Corp., San Diego, CA, USA. stephen.demarest@biogenidec.com
Mabs
|February 13, 2010
Summary
Monoclonal antibodies targeting Clostridium difficile toxin A
Area of Science:
- Microbiology
- Immunology
- Toxicology
Background:
- Clostridium difficile infection is a significant healthcare concern, primarily driven by toxins A and B.
- The cell wall binding (CWB) domains of these toxins are crucial for their adherence to host cells.
Purpose of the Study:
- To develop and evaluate murine monoclonal antibodies against the CWB domain of Clostridium difficile toxin A.
- To assess the neutralizing capacity of these antibodies, both individually and in combination.
Main Methods:
- Generation of murine monoclonal antibodies against the CWB domain of Clostridium difficile toxin A.
- Screening antibodies for their ability to neutralize toxin A.
- Investigating the mechanisms of neutralization, including surface coverage and inhibition of cell association.
Main Results:
- Three antibodies neutralized toxin A, recognizing multiple epitopes, suggesting surface coverage is important.
- A combination of two non-competing antibodies (3358 and 3359) demonstrated enhanced neutralization.
- Antibody 3358 increased detectable CWB domain presence, while 3359 inhibited CWB domain cell association.
Conclusions:
- Antibody combinations targeting broader epitope spaces on C. difficile toxin A's CWB domains offer enhanced neutralization.
- Multiple mechanisms, including increased surface coverage and inhibition of cell association, contribute to effective toxin neutralization.
- These findings suggest a promising strategy for developing improved therapeutics against C. difficile-associated diarrhea.
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