Escherichia coli F4 fimbriae specific lama single-domain antibody fragments effectively inhibit bacterial adhesion in vitro but poorly protect against diarrhea

M.M. Harmsen, C.B. van Solt, A. Hoogendoorn, F.G. van Zijderveld, T.A. Niewold, J. van der Meulen

    Research output: Contribution to journalArticleAcademicpeer-review

    47 Citations (Scopus)

    Abstract

    Oral administration of polyclonal antibodies directed against enterotoxigenic Escherichia coli (ETEC) F4 fimbriae is used to protect against piglet post-weaning diarrhoea. For cost reasons, we aim to replace these polyclonal antibodies by recombinant llama single-domain antibody fragments (VHHs) that can be produced efficiently in microorganisms. Six F4 fimbriae specific VHHs were isolated. The VHH that was produced at the highest level by yeast, K609, was further analysed. 3.8 mg/L K609 inhibited 90% of bacterial attachment to intestinal brush borders in vitro. Perfusion of a jejunal segment with at least 4 mg/L K609 reduced the ETEC-induced fluid loss, but only to 30%. Preventive administration of a high K609 dose (150 mg/(piglet day)) to piglets that were challenge infected with ETEC resulted in less severe diarrhoea only at 4 and 5 days post-infection, but did not improve average daily weight gain, ETEC shedding and piglet survival. Thus, we have shown that an antibody fragment that effectively inhibited in vitro ETEC adhesion to intestinal brush borders poorly protected piglets against experimental ETEC infection.
    Original languageEnglish
    Pages (from-to)89-98
    JournalVeterinary Microbiology
    Volume111
    Issue number1
    DOIs
    Publication statusPublished - 2005

    Keywords

    • egg-yolk antibodies
    • infectious intestinal-diseases
    • early-weaned piglets
    • monoclonal-antibodies
    • saccharomyces-cerevisiae
    • postweaning diarrhea
    • virulence factors
    • pigs
    • strains
    • secretion

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