Prolonged in vivo residence times of llama single-domain antibody fragments in pigs by binding to porcine immunoglobulins

M.M. Harmsen, C.B. van Solt, H.P.D. Fijten, M.C. van Setten

    Research output: Contribution to journalArticleAcademicpeer-review

    56 Citations (Scopus)

    Abstract

    The therapeutic parenteral application of llama single-domain antibody fragments (VHHs) is hampered by their small size, resulting in a fast elimination from the body. Here we describe a method to increase the serum half-life of VHHs in pigs by fusion to another VHH binding to porcine immunoglobulin G (pIgG). We isolated 19 pIgG-binding VHHs from an immunized llama using phage display. Six VHHs were genetically fused to model VHH K609 that binds to Escherichia coli F4 fimbriae. All six yeast-produced genetic fusions of two VHH domains (VHH2s) were functional in ELISA and bound to pIgG with high affinity (1¿33 nM). Four pIgG-binding VHH2s were administered to pigs and showed a 100-fold extended in vivo residence times as compared to a control VHH2 that does not bind to pIgG. This could provide the basis for therapeutic application of VHHs in pigs.
    Original languageEnglish
    Pages (from-to)4926-4934
    JournalVaccine
    Volume23
    Issue number41
    DOIs
    Publication statusPublished - 2005

    Keywords

    • mouth-disease virus
    • monoclonal-antibodies
    • saccharomyces-cerevisiae
    • escherichia-coli
    • protection
    • expression
    • transmission
    • vaccination
    • catabolism
    • diabodies

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