Appl Microbiol Biotechnol (2009) 84:1087–1094 ring in yeast, results in their rapid clearance in vivo due to binding to high-mannose receptors in the liver (Wright and Morrison 1994). This complicates the immunotherapeutic use of N-glycosylated FMDV-binding VHHs, which should be applied parenterally, but not of LT-binding VHHs, which should be delivered to the intestinal lumen by oral application. The use of recombinant yeast strains (Hamilton and Gerngross 2007) or plants (Strasser et al. 2008) that are engineered to produce proteins with human-like glycosyla- tion for production of glycosylated VHHs could prevent rapid in vivo clearance after parenteral application. Normally non-glycosylated VHHs can be converted to N-glycosylated VHHs by the introduction of potential N- glycosylation sites by site-directed mutagenesis (Sagt et al. 2000). 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