VHHs are variable fragments of camel single domain antibodies (sdAb). Thanks to their unique properties of size, solubility, stability, low immunogenicity, recognition of uncommon or hidden epitopes, VHHs present significant advantages compared to classical antibodies:
– Solubility: VHHs are naturally soluble in aqueous solution and do not have a tendency to aggregate, due to the substitution of hydrophobic by hydrophilic residues in the framework-2 region compared to conventional antibodies.
– Stability: VHHs are highly heat-stable. Indeed, VHH retain more than 80% of their binding activity after 1 week of incubation at 37°C. They are also stable when exposed to the denaturing effect of chaotropic agents and in the presence of proteases or extreme pH values.
– Expression: VHHs are expressed from a single gene requiring no post-translational modifications. The production process is scalable and expression systems other than bacteria can be used. There is no need of costly mammalian system for VHH expression.
– Immunogenicity: VHH antibodies have many important features, such as their low inherent toxicity, that make theme valuable for biotechnological and medical applications.
– Affinity: the affinity of VHHs is evaluated in one digit nanomolar range in their monovalent form. In multimeric forms, affinity can frequently be reached to picomolar.
– Functionality: VHHs can bind into cavities or active sites of enzyme targets. Other important features are ease and speed of drug discovery and ease of manufacture.