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VHH Antibodies

Specifica delivers VHH antibody libraries and discovery campaigns with the same expertise we apply to our ScFv and Fab libraries. 

 

Read about our success in developing single-domain (VHH) antibodies from our libraries in this June 2025 article in mAbs.

 

Recombinant VHH libraries from Specifica deliver:

  • Fully humanized VHHs – not just the frameworks, but also the CDRs are humanized, providing improved safety and therapeutic efficacy
  • Broad diversity – our phage display libraries far exceed the diversity of immunization, and sorting via yeast display provides additional capabilities to enable selection for desired properties
  • High specificity – controlled selection conditions allow you to focus on specific regions of your target antigen
  • High affinity – exceptional binding due to the preserved CDR regions, often reaching into the sub-nanomolar range
    • >50% of campaigns yield at least one subnanomolar binder
    • >50% of binders <10nM and ~5% of binders are subnanomolar
  • High affinity and specificity – combined, high affinity and desired specificity can provide a drug-like VHH straight from selection, often without the need for additional improvement
  • High developability – over 70% of VHHs have two or fewer biophysical liabilities 

 

Together, our proven scaffolds, desired specificity, high affinity and excellent developability can provide a drug-like VHH straight from selection, often without the need for additional improvements.

VHH

What are VHH antibodies and what are their advantages?

  • VHHs are single-domain antibodies based on camelid antibodies
  • VHHs are much smaller than traditional antibodies, enabling them to bind to challenging targets including “hidden” epitopes, less easily accessible by traditional antibodies
  • VHHs are generally more diverse than other antibody fragments, due to their unique structure, with elongated CDR1 and CRD3 loops
  • VHHs are stable and soluble, making them well suited to meet the developability requirements of consistent quality and reduced variability

What is Specifica's approach to building VHH libraries?

  • Our VHH libraries are based on four well-behaved therapeutic VHH molecules, with HCDR1 and 2 natural replicated diversity from rearranged VH3 family genes;
  • The CDRs are filtered for correct folding via protein A selection (protein A binding being an inherent property of the VH3-23 gene family)
  • Only well-folded CDRs are allowed in the final library, enhancing its functionality and overall quality.
VHH-schematic

Email us to learn more or complete the contact us form and we’ll reach out to you.