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Orally active bivalent VHH construct prevents proliferation of F4+ enterotoxigenic Escherichia coli in weaned piglets

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  • Berthe Katrine Fiil, Technical University of Denmark
  • ,
  • Sandra Wingaard Thrane, Bactolife ApS
  • ,
  • Michael Pichler, Technical University of Denmark
  • ,
  • Tiia Kittilä, Technical University of Denmark
  • ,
  • Line Ledsgaard, Technical University of Denmark
  • ,
  • Shirin Ahmadi, Technical University of Denmark
  • ,
  • Grith Miriam Maigaard Hermansen, Technical University of Denmark, Bactolife ApS
  • ,
  • Lars Jelsbak, Technical University of Denmark
  • ,
  • Charlotte Lauridsen
  • Susanne Brix, Technical University of Denmark
  • ,
  • Andreas Hougaard Laustsen, Technical University of Denmark, Bactolife ApS

A major challenge in industrial pig production is the prevalence of post-weaning diarrhea (PWD) in piglets, often caused by enterotoxigenic Escherichia coli (ETEC). The increased use of antibiotics and zinc oxide to treat PWD has raised global concerns regarding antimicrobial resistance development and environmental pollution. Still, alternative treatments targeting ETEC and counteracting PWD are largely lacking. Here, we report the design of a pH, temperature, and protease-stable bivalent VHH-based protein BL1.2 that cross-links a F4+ ETEC model strain by selectively binding to its fimbriae. This protein inhibits F4+ ETEC adhesion to porcine epithelial cells ex vivo and decreases F4+ ETEC proliferation when administrated as a feed additive to weaned F4+ ETEC challenged piglets. These findings highlight the potential of a highly specific bivalent VHH-based feed additive in effectively delimiting pathogenic F4+ ETEC bacteria proliferation in piglets and may represent a sustainable solution for managing PWD while circumventing antimicrobial resistance development.

Original languageEnglish
Article number104003
Publication statusPublished - Apr 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

    Research areas

  • Infection control in health technology, Microbiology, Porcine medicine

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