Reformat into VHH

Typically, antibodies are made up of two heavy and two light chains, and both chains contribute to the antigen-binding site. Apart from these common antibodies, those from camelids, llamas, or sharks are comprised of only heavy chains. The antigen-binding site of these heavy chain antibodies (HcAbs) is composed by a single domain, referred to VHH in camelid HcAbs and VNAR in shark HcAbs. Besides, the CDR3 region of these single domain antibodies (sdAbs) comprises the extraordinary capacity to form long fingerlike extensions which enable to extend into cavities on antigens. Due to the special features of VHHs (easy to clone and express, bind antigens as effectively as full-length antibodies), they are being extensively studied as potential therapeutic, diagnostic and imaging tools. As an undisputed lead in the antibody engineering area, Creative Biolabs provides a full range of reformatting services for customers to obtain your ideal VHH antibody.

Reformat into VHH

Typically, reformat engineering of cAbs to increase therapeutic function needs knowledge of the differences of sequence and structural features between cAbs and common antibodies. cAb VHH x-ray crystal structures display the general immunoglobulin fold, usually most similar to the human variable heavy chain (VH) of family III. Nevertheless, many differences can be seen in the CDRs, and some long CDR H3s bend and make contacts with the framework region of the cAb VHH, which in a common antibody, would have been in contact with VL. In order to accelerate the cAb VHH structure determination process and better service for reformatting antibodies into VHH, we have developed an advanced in silico platform comprised several techniques, such as homology modeling, molecular dynamics simulation, in-house algorithm, and antibody molecule model analysis.

Nowadays, more than 11 marketed classical humanized antibodies have been designed by combining the reliance on homology modeling with the paucity in cAb VHH structures. Thus, with our experience scientists and full-scale platforms, we are confident in providing high quality reformatting into VHH services to promote your antibody project.

Fig 1. Model of small oligomer of ASCCARD complexed by VHHASC. (hmidt, F. I., 2016)

Properties of VHH Fragments

There are a number of features made VHHs different to common antibodies and give their unique properties. Following are several advantages of VHHs over murine antibodies:

• Weakly immunogenic in humans, on account of the genes encoding them have high sequence homology with genes belonging to the human VH families 3 and 4.
• Easy to generate via different expression systems with high yields.
• According to their sequence variability, VHHs can recognize several epitopes, ranging from small haptens to binding sites of enzymes.
• Due to their small size, VHHs enable to penetrate tissues, pass through barriers (the blood-brain barrier) and bind epitopes that unable by conventional antibodies.
• VHHs possess high solubility and stability in denaturing states or high temperatures.

With our comprehensive VHH antibody reformatting services, designing and engineering novel antibodies with desired therapeutic properties is available. We customize the service according to the specific requirements from the customers. We also provide other structure-based antibody reformatting services. Please contact us for more information and a detailed quote.

References

1. Smolarek, D., (2012). “Variable fragments of heavy chain antibodies (VHHs): a new magic bullet molecule of medicine?.” Advances in Hygiene & Experimental Medicine/Postepy Higieny i Medycyny Doswiadczalnej, 66.
2. Sircar, A., (2011). “Analysis and modeling of the variable region of camelid single-domain antibodies.” The Journal of Immunology, 186(11), 6357-6367.
3. Schmidt, F. I., (2016). “A single domain antibody fragment that recognizes the adaptor ASC defines the role of ASC domains in inflammasome assembly.” Journal of Experimental Medicine, jem-20151790.

All services provided on this site are intended to support preclinical research only. Do not use our services or final products on humans.