Selection and production of camelid VHHs/nanobodies

This PBSIM service offers the expertise for selection of camelid VHHs/nanobodies followed by their production and characterization (SPR, BLI, micro-cal).

The use of single-domains from camelid immunoglobulins, termed VHHs or nanobodies (Fig. 1), has seen an increasing growth in recent years. The usefulness of nanobodies in structural biology is now firmly established, as they provide access to new epitopes in concave and hinge regions – and stabilize them.

Remarkable results have been achieved by using nanobodies with flexible multi-domain proteins, large complexes and, last but not least, membrane proteins such as GPCRs or other receptors or channels. The structural biology group at the AFMB lab has been among the pioneers in the work on VHHs and nanobodies.

This tecnological facility offers immunization of llamas (Lama glama glama) or camels (Camelus dromedarius) in view to obtain target specific libraries, panning of these libraries by phage display from which several vHHs/nanobodies are cloned (service 1), expressed (service 2) and characterized (service 3) (Fig. 2). We also propose our “naive” library obtained by gathering the lymphocytes of non-immunized animals – in our case, 3 camels and 4 llamas. Randomizing one of the three CDRs (generally CDR3) from a selected VHH/nanobody followed by a new panning cycle (service 4) leads to sub-nanomolar affinities.