Abstract
Due mainly to properties such as high affinity and antigen specificity, antibodies have become important tools for biomedical research, diagnosis, and treatment of several human diseases. When the objective is to administer them for therapy, strategies are used to reduce the heterologous protein immunogenicity and to improve pharmacokinetic and pharmacodynamic characteristics. Size minimization contributes to ameliorate these characteristics, while preserving the antigen–antibody interaction site. Since the discovery that camelids produce functional antibodies devoid of light chains, studies have proposed the use of single domains for biosensors, monitoring and treatment of tumors, therapies for inflammatory and neurodegenerative diseases, drug delivery, or passive immunotherapy. Despite an expected increase in antibody and related products in the pharmaceutical market over the next years, few research initiatives are related to the development of alternatives for helping to manage neglected tropical diseases (NTDs). In this review, we summarize developments of camelid single-domain antibodies (VHH) in the field of NTDs. Particular attention is given to VHH-derived products, i.e., VHHs fused to nanoparticles, constructed for the development of rapid diagnostic kits; fused to oligomeric matrix proteins for viral neutralization; and conjugated with proteins for the treatment of human parasites. Moreover, paratransgenesis technology using VHHs is an interesting approach to control parasite development in vectors. With enormous biotechnological versatility, facility and low cost for heterologous production, and greater ability to recognize different epitopes, VHHs have appeared as an opportunity to overcome challenges related to the prevention, detection, and control of human diseases, especially NTDs.
Highlights
Carole Henry, University of Chicago, United States Joseph Ashour, Icahn School of Medicine at Mount Sinai, United States
A similarity greater than 80% with the FRs of human VH regions and high renal clearance justify their low immunogenicity [20, 32]. Their high solubility, affinity, and specificity for molecular targets, stability, flexibility related to the construction of different formats, multiple routes of administration, humanized construction possibilities, Figure 1 | Representation of immunoglobulin (Ig) G molecules and uses of VHHs in neglected tropical diseases (NTDs). (A) Conventional IgG showing heavy and light domains that perform fragment antigen binding (Fab) and fragment crystallizable (Fc) regions, and camelid heavy chain [heavy-chain antibody (HCAb)] IgG. (B) Comparison between VH and VHH domains on the amino acid sequence level
Trypanosoma cruzi is the etiological agent of Chagas disease (CD), an anthropozoonosis endemic to the American continent [70, 71], that affects about 10–12 million people worldwide [72]
Summary
The advent of hybridoma technology provided a great development in antibody engineering [1]. The strategy to minimize antibody size preserves antigen– antibody binding sites generating monovalent [fragment antigen binding (Fab)] fragments from IgGs, single-chain variable fragments (scFv), as well as single-domain antibodies [9] This approach aims to improve bioavailability and reduce immunogenicity, when the objective is to use them for pharmacological treatment. A similarity greater than 80% with the FRs of human VH regions and high renal clearance justify their low immunogenicity [20, 32] Their high solubility, affinity, and specificity for molecular targets, stability, flexibility related to the construction of different formats (monomers, dimers—mono- or bispecifics, fused to drugs, etc.), multiple routes of administration, humanized construction possibilities,. Public–private partnerships have emerged to develop medicines and health technologies to circumvent the challenges faced in NTDs [47]
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