Toxin-Specific Antibodies for the Treatment of Clostridium difficile Current Status and Future Perspectives 英文参考文献.docVIP

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Toxin-Specific Antibodies for the Treatment of Clostridium difficile Current Status and Future Perspectives 英文参考文献.doc

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Toxin-Specific Antibodies for the Treatment of Clostridium difficile Current Status and Future Perspectives 英文参考文献

Toxins 2010, 2, 998-1018; doi:10.3390/toxins2050998 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Toxin-Specific Antibodies for the Treatment of Clostridium difficile: Current Status and Future Perspectives ? Greg Hussack and Jamshid Tanha * Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario, K1A 0R6, Canada; E-Mail: Greg.Hussack@nrc-cnrc.gc.ca ? This is NRC publication number 42534. * Author to whom correspondence should be addressed; E-Mail: Jamshid.Tanha@nrc-cnrc.gc.ca; Tel.: +1-613-990-7206; Fax: +1-613-952-9092. Received: 26 March 2010; in revised form: 29 April 2010 / Accepted: 5 May 2010 / Published: 7 May 2010 Abstract: Therapeutic agents targeting bacterial virulence factors are gaining interest as non-antibiotic alternatives for the treatment of infectious diseases. Clostridium difficile is a Gram-positive pathogen that produces two primary virulence factors, enterotoxins A and B (TcdA and TcdB), which are responsible for Clostridium difficile-associated disease (CDAD) and are targets for CDAD therapy. Antibodies specific for TcdA and TcdB have been shown to effectively treat CDAD and prevent disease relapse in animal models and in humans. This review summarizes the various toxin-specific antibody formats and strategies under development, and discusses future directions for CDAD immunotherapy, including the use of engineered antibody fragments with robust biophysical properties for systemic and oral delivery. Keywords: Clostridium difficile; Clostridium difficile-associated disease; toxin; antibody; single-domain antibody; neutralization; therapy 1. Introduction Clostridium difficile is a Gram-positive, endospore-forming, anaerobic, gastrointestinal pathogen that is a leading cause of nosocomial infections in developed nations. The bacterium is transmitted by Toxins 2010, 2 999 the fecal-oral route and can readily colonize persons