Neutralization of Clostridium difficile toxin B with VHH-Fc fusions targeting the delivery and CROPs domains.

ABSTRACT: An increasing number of antibody-based therapies are being considered for controlling bacterial infections, including Clostridium difficile by targeting toxins A and B. In an effort to develop novel C. difficile immunotherapeutics, we previously isolated several single-domain antibodies (VHHs) capable of toxin A neutralization through recognition of the extreme C-terminal combined repetitive oligopeptides (CROPs) domain, but failed at identifying neutralizing VHHs that bound a similar region on toxin B. Here we report the isolation of a panel of 29 VHHs targeting at least seven unique epitopes on a toxin B immunogen composed of a portion of the central delivery domain and the entire CROPs domain. Despite monovalent affinities as high as KD = 70 pM, none of the VHHs tested were capable of t

SUBMITTER: Hussack G 

PROVIDER: S-EPMC6291252 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature