Single-Domain Antibodies As Therapeutics against Human Viral Diseases

Abstract

In full-size formats, monoclonal antibodies have been highly successful as therapeutics against cancer and immune diseases. However, their large size leads to inaccessibility of some epitopes and relatively high production costs. As an alternative, single-domain antibodies (sdAbs) offer special advantages compared to full-size antibodies, including smaller size, larger number of accessible epitopes, relatively low production costs and improved robustness. Currently, sdAbs are being developed against a number of viruses, including human immunodeficiency virus-1 (HIV-1), influenza viruses, hepatitis C virus (HCV), respiratory syncytial virus (RSV), and enteric viruses. Although sdAbs are very potent inhibitors of viral infections, no sdAbs have been approved for clinical use against virial infection or any other diseases. In this review, we discuss the current state of research on sdAbs against viruses and their potential as therapeutics against human viral diseases.

Selective Engagement of FcγRIV by a M2e-Specific Single Domain Antibody Construct Protects Against Influenza A Virus Infection

“…Since the reported discovery of heavy chain-only antibodies in camelids in 1993, recombinant single domain proteins comprising the variable domain of these antibodies (VHHs also known as Nanobodies R ) have been used in numerous therapeutic applications (21). In the context of viral infections, various virus-neutralizing VHHs have been described that can interfere with different steps in the viral life cycle (22). Due to their outstanding stability and solubility, as well as their small size (∼15 kDa), ease of production and formatting flexibility, they are highly versatile building blocks for the development of new antivirals.…”

Engineering a Novel Antibody-Peptide Bispecific Fusion Protein Against MERS-CoV

“…Monoclonal antibodies represent one of the most promising immunotherapeutic agents for the treatment of cancers and infectious diseases [7,[47][48][49][50][51][52]. Previously, we used RBD of MERS-CoV S protein to screen a non-immune phage-displayed Fab library and identified a highly potent human neutralizing mAb m336 and a panel of other mAbs against MERS-CoV [34,36,37].…”

Fully human single-domain antibodies against SARS-CoV-2

“…The large-scale production of mAbs typically takes at least 3 to 6 months, making them difficult to be timely produced and used in an epidemic setting. An attractive alternative for mAbs is single-domain antibodies from camelid immunoglobulins, termed VHH or nanobodies that are the smallest naturally occurring antigen-binding protein domains with a molecular weight of 12-15 kDa 11 . Their small size provides several advantages over conventional mAbs (150 kDa), including larger number of accessible epitopes, relatively low production costs, and easiness of rapid production at kilogram scale in prokaryotic expression systems.…”

“…However, the camelid origin of nanobodies limits their application as therapeutics in human. To reduce the risk of immunogenicity, strategies for humanization of camelid nanobodies have become available in recent years but suffered from time- and labor-consuming 11 . Besides, humanized nanobodies still retain a small number of camelid residues, especially those within the framework region 2 (FR2), in order to maintain the solubility and antigen-binding affinity of parental antibodies 11,14 .…”