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Review
. 2017 Dec 13:8:1802.
doi: 10.3389/fimmu.2017.01802. eCollection 2017.

Single-Domain Antibodies As Therapeutics against Human Viral Diseases

Yanling Wu  1 , Shibo Jiang  1 , Tianlei Ying  1
Affiliations
Review

Single-Domain Antibodies As Therapeutics against Human Viral Diseases

Yanling Wu et al. Front Immunol. .

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.

Keywords: antiviral therapeutics; human immunodeficiency virus-1; nanobody; single-domain antibody; viral disease.

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Figures

Figure 1
Figure 1
Representation of single-domain antibodies (sdAbs) and their characteristics. (A) Representation of camelid sdAb framework (FR) and complementarity-determining (CDR) regions, showing hydrophilic amino acids (Phe42, Glu49, Arg50, Gly52) in the FR2 region compared to conventional human VH (Val42, Gly49, Leu50, Trp52). (B) Schematic representation of sdAb-based engineered antibody constructs. (C) Neutralizing sdAb JM4 (PDB identifier 4LAJ) in complex with HIV-1 YU2 envelope gp120 glycoprotein, showing CDR1 (yellow), CDR2 (orange), and CDR3 (blue) and comparing CDR3 between human VH domain HEL4 (blue) (PDB identifier 1OHQ) and HIV-1 gp41 MPER-specific llama VHH 2H10 (green) (PDB identifier 4B50).
Figure 2
Figure 2
Mechanisms of single-domain antibody (sdAb)-based therapeutics against viruses. Mechanism A: preventing entry of the viral particle into host cells by targeting viral envelope proteins or receptors that mediate cell binding and membrane fusion; mechanism B: blocking specific interactions between virus/virus or virus/host proteins, promoting aberrant interactions, binding in the active sites of enzymes, or through recognition or stabilization of distinct conformations of their targets; and mechanism C: specifically killing virus-infected cells by drug-conjugated or toxin-fused sdAbs.
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