Complementarity-Determining Region 3 (CDR3) of the Heavy Chain Only Antibodies: Therapeutic Perspectives

Neuroinfections are difficult and time-consuming to treat. The main bottleneck in therapy is drugs’ inability to enter the central nervous system (CNS) via the blood-brain barrier (BBB). Because the diffusion of conventional antibodies in tissues is limited by their large size (150 kDa), it is necessary to find an antibody fragment that can cross the BBB and treat CNS infections. Camelid heavy chain only antibodies, also known as nanobodies, possess a unique Variable domain of a Heavy chain (VHH). The VHH could be used as an alternative to conventional antibodies and have enormous potential in a wide range of medical and bio-technology fields. The VHH with an average molecular weight of 15 kDa can diffuse nearly four times better in tissues and tumours than common antibodies. A VHH is made up of four framework regions (FR1‒4) and three hypervariable complementarity-determining regions (CDR1‒3), with CDR3 being particularly important in interaction with pathogen epitopes. Experimental results have shown that the CDR3 domain alone can bind to epitopes and may contribute to reduce the size of the antigen-recognizing molecule, allowing it to be used more effectively to diffuse much better in tissues, and as well as to cross the BBB and biodistributed in CNS.