Exploiting Nanobodies® for diagnosis and treatment of African Trypanosomiasis

Trypanosomiasis is a disease with a devastating socio-economic impact in Sub-Saharan Africa through the direct infection of humans and livestock. While an estimated 60 million people in 36 countries are under risk of infection, the economic cost linked to the yearly death of more than 3 million infected cattle is approximately US$4.75bn, not including the impact of socio-cultural and food insecurity repercussions of the diseases. Even though a diagnostic test and treatments exist, both suffer from serious drawbacks. While current diagnostics have limited specificity, current treatment schemes often result in severe negative side effects in patients and even can be lethal in up to 5–10 per cent of treated individuals.

The NANOTRYP* project, initiated under the EU FP7 research call Health-2007-2.3.4-1, will address the problems identified above with a Nanobody®-based approach to the development of new simple-to-use diagnostic tests and treatment methods for trypanosomiasis. Nanobodies® are extremely tiny ‘nanometer-sized’ fragments of single-chain camelid antibodies. They possess unique features that enable them to bind targets that are not accessible to standard antibodies. NANOTRYP is using these fragments to develop an innovative dipstick test, thus eliminating the need for any equipment. The aim is to use Nanobodies® for recognition of intact parasites and parasite molecules that can be released during sample preparation. In the search for novel treatment, Nanobody®-targeted drug delivery is being explored, aiming at site-specific drug delivery of the existing anti-trypanosomals such as Pentamidine, DFMO, Suramine, Melarsoprol and Nifurtimox. This would allow a drastic reduction of the drug dosis needed for effective treatment, hence reducing the risk of treatment-associated side effects.

Despite tremendous efforts to improve diagnostic tools for both Human African Trypanosomiasis (HAT) and Animal Africa Trypanosomiasis (AAT) in the past, and the continued efforts to find new cures, progress in the fight against trypanosomiasis has been slow. With no anti-trypanosome vaccination strategy available, and no results suggesting a solution for this problem, combating trypanosomiasis will also in the near future fully rely on diagnosis and treatment of infected individuals and animals. Hence, under NANOTRYP a consortium of European and African laboratories have now joined forces in order to try and push new breakthroughs in the field. The consortium includes European members of VIB – Belgium, FIBAO – Spain, FIND – Switzerland and ARTTIC – Belgium, and African members of IPR – Kenya and EUM – Mozambique. NANOTRYP foresees an important involvement of the African research community both at the level of fundamental science, aiming at the acquisition of a better understanding of trypanosomiasis, as well as at the level of disease diagnostics, treatment and community-awareness building. The project’s access strategy, which will guarantee sustained availability of the technology, includes advocacy and awareness campaigns at international, national and community levels and will urge governments to allocate adequate resources for such programmes. Diagnostics-development companies have, meanwhile, successfully been convinced to manufacture Nanobody®-based tests at affordable prices.

Figure 1: Schematic structure of a conventional antibody, a camel heavy-chain antibody and the tiny derived Nanobody® fragment obtained from the camel antibody.

Figure 2: Trypanosome-infected blood sample in which parasites are visualised for easy detection using a fluorescent tagged Nanobody®.

Figure 3: NANOTRYP logo.

Stefan Magez, Research Professor, PhD, Ir. Vrije Universiteit Brussel,
Group Leader, Flanders Institute for Biotechnology,
Adjunct Assistant Professor, University of Massachusetts

VIB Department of Molecular and Cellular Interactions
Laboratory for Cellular and Molecular Immunology
Building E8.01
Pleinlaan 2, B-1050 Brussels, Belgium

Tel: +32 2 629 1976

Fax: +32 2 629 1981

Email: stemagez@vub.ac.be

Web: www.nanotryp.eu