Abstract
African trypanosomes are strictly extracellular protozoan parasites that cause diseases in humans and livestock and significantly affect the economic development of sub-Saharan Africa. Due to an elaborate and efficient (vector)–parasite–host interplay, required to complete their life cycle/transmission, trypanosomes have evolved efficient immune escape mechanisms that manipulate the entire host immune response. So far, not a single field applicable vaccine exists, and chemotherapy is the only strategy available to treat the disease. Current therapies, however, exhibit high drug toxicity and an increased drug resistance is being reported. In addition, diagnosis is often hampered due to the inadequacy of current diagnostic procedures. In the context of tackling the shortcomings of current treatment and diagnostic approaches, nanobodies (Nbs, derived from the heavy chain-only antibodies of camels and llamas) might represent unmet advantages compared to conventional tools. Indeed, the combination of their small size, high stability, high affinity, and specificity for their target and tailorability represents a unique advantage, which is reflected by their broad use in basic and clinical research to date. In this article, we will review and discuss (i) diagnostic and therapeutic applications of Nbs that are being evaluated in the context of African trypanosomiasis, (ii) summarize new strategies that are being developed to optimize their potency for advancing their use, and (iii) document on unexpected properties of Nbs, such as inherent trypanolytic activities, that besides opening new therapeutic avenues, might offer new insight in hidden biological activities of conventional antibodies.
Highlights
African trypanosomiasis (AT), caused by strictly extracellular unicellular flagellated protozoan parasites belonging to the genus Trypanosoma, is a “neglected” disease of medical and veterinary importance that significantly affects the socioeconomic development of sub-Saharan Africa [1,2,3,4,5]
Animal African trypanosomiasis (AAT) or Nagana is the second form of AT affecting sub-Saharan Africa, which is mainly caused by Trypanosoma congolense, Trypanosoma vivax, and to a lesser extent Trypanosoma brucei brucei, whereas Surra and Dourine are forms of AAT caused by Trypanosoma evansi and Trypanosoma equiperdum, respectively [15,16,17]
Nbs have been found to be valuable tools in the field of AT both at the level of diagnosis and treatment. They were shown to have potential to circumvent problems encountered with antibody-based detection systems and in addition allow the development of antigen-based approaches that were so far lacking [32]
Summary
African trypanosomiasis (AT), caused by strictly extracellular unicellular flagellated protozoan parasites belonging to the genus Trypanosoma, is a “neglected” disease of medical and veterinary importance that significantly affects the socioeconomic development of sub-Saharan Africa [1,2,3,4,5]. Nbs exhibit characteristic features such as (i) a nanomolar affinity for their target [39], (ii) a unique epitope recognition spectrum different from conventional antibodies, thereby allowing detection of both free antigens and those bound by host antibodies [40], (iii) high solubility [40], (iv) easy tailorability (multimerization or tagging) for molecular imaging and drug-delivery applications [41,42,43,44], and (v) small size that circumvents problems of tissue or blood–brain barrier (BBB) penetrability [44, 45]. We will give an overview of how the Nb technology can be implemented in the fight against AT both at the level of diagnosis and treatment and how acquired knowledge on Nbs in AT might lead to new insights in the function of conventional antibodies in the immune system
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