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Exploiting Nanobodies in development of new diagnostic tools and treatment methods for Trypanosomiasis

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New diagnostic tools for trypanosomiasis

Researchers from all over the world engaged in activities towards the development of novel diagnostic tools against trypanosomiasis. The deliverables of the NANOTRYP study could alleviate the heavy socioeconomic burden of endemic countries.

Health

The protozoan Trypanosome is endemic in Sub-Saharan Africa and causes trypanosomiasis, also known as sleeping sickness, in both humans and animals. Transmission occurs through tsetse flies and the therapeutic efficacy of existing drugs depends on the stage of disease. Patients diagnosed early have good prospects while advanced stage disease is more difficult to treat and drug administration is associated with high toxicity and mortality. As a result, there is a great need to develop sensitive tools for improving early disease diagnosis. The EU-funded NANOTRYP project proposed to generate novel antibodies, known as Nanobodies® capable of recognising all four major African trypanosome species. The rational was to develop an easy-to-use kit for screening trypanosomiasis which could replace the current anti-parasite antibody diagnostic assay. Nanobodies® are short antibodies that were discovered by chance over 20 years ago in camelids. They are in the nanometer range and demonstrate high affinity for the target antigen. NANOTRYP partners explored the properties of these unique antibodies by producing them from recombinant libraries. Selection was performed against soluble extracts of trypanosomes and promising nanobody candidates against conserved trypanosome species antigens were used to design an ELISA assay. Anti-trypanosome nanobodies were also used for parasite detection in the blood of experimentally infected animals. However, since the parasite levels in infected human blood are significantly lower, partners decided to use nanobodies in antigen-capturing methods. Furthermore, nanobodies were exploited as drug targeting molecules and significantly increased the efficacy of drug delivery tenfold. The future testing of nanobodies was enabled through the development of Trypanosomiasis models in non-human primates. The NANOTRYP consortium also trained the African teams and helped to build-up the research capacity of participating institutes. Through trypanosomiasis awareness campaigns it provided information on disease transmission, control and treatment. Taken together, the nanobody technique avoids expensive, labour intensive molecular techniques and offers high specificity and sensitivity for trypanosome antigens. With promising candidates against both human and animal trypanosomes, partners hope to improve disease diagnosis and treatment outcome.

Keywords

Trypanosomiasis, diagnosis, nanobodies, antibodies, recombinant, assay, antigen-capturing, drug

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