Camelid Single-Domain Antibodies As an Alternative to Overcome Challenges Related to the Prevention, Detection, and Control of Neglected Tropical Diseases

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.

Peptide and protein nanoparticle conjugates: versatile platforms for biomedical applications

“…These smaller targeting groups can be produced via genetic engineering or careful protease-mediated Ab digestion, generating motifs which overcome the disruptive size, potential immunogenicity, and high cost of the parent Ab 342. Both full length and fragment Abs have been extensively used to target the delivery of NP cargoes, as have naturally occurring single domain camelid Abs 349. Tumours have been particularly widely targeted due to the frequency with which cell-surface receptors are overexpressed and can thus be used as a site for selective delivery 12.…”

Anticuerpos de cadena única de alpaca para la detección de antígenos de Fasciola hepatica

“…Con el objetivo de contar con nuevas moléculas para el desarrollo de pruebas de diagnóstico de fascioliasis usando anticuerpos de cadena única de alpacas, se han sintetizado genotecas de cADN de VHH (1x10 7 clones) para seleccionar VHH que se unen específicamente al antígeno ES de F. hepatica por despliegue diferencial de fagos. Esta estrategia se ha aplicado en otros agentes infecciosos (10,11,12) . La genoteca de cADN de VHH tiene una alta representación de los anticuerpos de cadena única de los grupos IgG2 e IgG3 (5x10 7 clones) derivados del ARN de células blancas de una alpaca inmunizada con ES.…”

How can monoclonal antibodies be harnessed against neglected tropical diseases and other infectious diseases?

“…Common for these therapies is that they all involve intravenous administration of monoclonal immunoglobulin G (IgG) type antibodies. In the future, other antibody formats and other routes of administration, as well as the use of DNA vaccines, may find their way to the market, both for human and veterinary indications [50][51][52][53][54][55].…”