Prolonged in vivo residence times of llama single-domain antibody fragments in pigs by binding to porcine immunoglobulins
MM Harmsen, CB Van Solt, HPD Fijten, MC Van Setten - Vaccine, 2005 - Elsevier
MM Harmsen, CB Van Solt, HPD Fijten, MC Van Setten
Vaccine, 2005•ElsevierThe 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 …
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 …
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 (1–33nM). 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.
Elsevier