Innovative anti-VHH antibodies : SYnAbs enters the nano-world


Who hasn't heard about VHH?

As evolution progresses, camelids have developed the innate ability to generate small immunoglobulins (80 kDa) lacking light chains regions, so-called heavy chain-only antibodies (HCAbs). The smallest functional fragment of this HCAb is a single chain domain named VHH. In other words, when working with a small portion of a small camelid antibody, we play with a very tiny entity (2.5 nm in diameter and about 4 nm in length) which take the name of Nanobody (Nb).

The VHH (~15 kDa) have been honored by Ablynx, the company with the most important portfolio in the field, and the first approved therapeutic VHH « caplacizumab » for the use in adults with acquired thrombotic thrombocytopenic purpura (aTTP) disease.

Nbs offer many advantages, including :

  • a relatively short half-life (well suited for in-vivo imaging applications),
  • the ability to penetrate the most difficult-to-access tissues (such as the blood-brain barrier)
  • potential interaction with intracellular (and potentially deemed unreachable) targets,
  • being able to reach epitopes impossible to access for conventional antibodies (convex surface topology as compared to the flat or concave topologies found on conventional antibody paratope),
  • being produced in a simpler and less costly way (given their single-domain and hydrophilic nature, Nbs are well expressed in bacteria and yeasts).

And it is only a "small" ☺ overview of the many qualities of these entities…

mAbexperts (https://www.mabexperts.com/en) has developed unique know-how in the generation of VHH, through custom DNA & protein immunization in llama and alpaca, library generation and final production in bacteria (Escherichia coli) and yeast (Pichia pastoris and Saccharomyces cerevisiae).

At QVQ (http://www.qvquality.com) in Utrecht, the construction of phage-display libraries is performed by cloning of amplified VHH repertoires with minimal modification, thus presenting an authentic picture of in vivo-matured heavy chain repertoire diversity.

Furthermore, Nbs have other advantages over conventional Abs, such as their unique physical and chemical robustness. When the appropriate selection strategies are performed, Nbs can be selected with remarkable stability under certain harsh conditions, including extreme temperatures, the presence of proteases, high pressure, or low pH.

Building on the natural synergy with QVQ, and to support the growing demand of VHH technologies in immunotherapeutics development, diagnostic assay, and medical imaging applications,

SYnAbs (https://www.synabs.be) now offers secondary monoclonal antibodies for the detection, quantification, and purification of camelid antibodies.

These innovative rat anti-VHH monoclonal antibodies are now available on demand.

Active in VHH field? Don’t hesitate to reach us for more details!