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Orally active bivalent VHH construct prevents proliferation of F4+ enterotoxigenic Escherichia coli in weaned piglets. 2022

Berthe Katrine Fiil, and Sandra Wingaard Thrane, and Michael Pichler, and Tiia Kittilä, and Line Ledsgaard, and Shirin Ahmadi, and Grith Miriam Maigaard Hermansen, and Lars Jelsbak, and Charlotte Lauridsen, and Susanne Brix, and Andreas Hougaard Laustsen
Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 224, 2800 Kongens Lyngby, Denmark.

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.

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