title: Intravenous adenovirus expressing a multi-specific, single-domain antibody neutralizing TcdA and TcdB protects mice from Clostridium difficile infection.
abstract: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and colitis in developed countries. The disease is mainly mediated via two major exotoxins TcdA and TcdB secreted by the bacterium. We have previously developed a novel, potently neutralizing, tetravalent and bispecific heavy-chain-only single domain (VHH) antibody to both TcdA and TcdB (designated as ABA) that reverses fulminant CDI in mice. Since ABA has a short serum half-life, in this study a replication-deficient recombinant adenovirus expressing ABA was generated and the long-lasting expression of functional ABA was demonstrated in vitro and in vivo Mice transduced with one dose of the adenovirus displayed high levels of serum ABA for more than1 month and were fully protected against systemic toxin challenges. More importantly, the ABA delivered by the adenovirus protected mice from both primary and recurrent CDI. Thus, replication-deficient adenoviral vector may be used to deliver neutralizing antibodies against the toxins in order to prevent CDI and recurrence.
authors: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
authors: Zhiyong
authors: Z
authors: Yang
authors: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
authors: Lianfa
authors: L
authors: Shi
authors: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
authors: Hua
authors: H
authors: Yu
authors: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
authors: Yongrong
authors: Y
authors: Zhang
authors: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
authors: Kevin
authors: K
authors: Chen
authors: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
authors: Ashley
authors: A
authors: Saint Fleur
authors: Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
authors: Guang
authors: G
authors: Bai
authors: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA hfeng@umaryland.edu.
authors: Hanping
authors: H
authors: Feng
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000235:genetics* / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D002460:Cell Line; D016360:Clostridioides difficile / Q000276:immunology*; D003015:Clostridium Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000628:therapy; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000276:immunology; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D007167:Immunotherapy; D051379:Mice; D009500:Neutralization Tests; D061905:Single-Domain Antibodies / Q000097:blood / Q000235:genetics* / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D061905:Single-Domain Antibodies; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile
keywords: Clostridium difficile; VHH, adenovirus; immunotherapy; toxins, antibody