African Trypanosomiasis is an excellent model system to study immune escape by invading extracellular pathogens. Being under continuous attack of the host humoral response, trypano-somes developed a system of antigenic variation of their surface coat in order to evade anti-body-mediated immune destruction. In-depth studies on the mechanisms of antigenic varia-tion have resulted in the understanding of both structural and genetic aspects of the surface coat organization of trypanosomes, and the variant-specific glycoproteins (VSG) itself, i.e. the protein that provides the interface between the parasite and the host immune system (see chapters 1 and 3). To date, the current hypothesis of VSG-mediated antibody escape implies that during infection the host is capable of mounting an ever changing antibody repertoire, which allows to target in a specific manner each new trypanosome wave. In this chapter, a number of recent insights will be discussed, that highlight the complexity of this system. In-deed, experimental data obtained in rodent T. brucei models suggest that anti-VSG responses are very short lived, and no memory is mounted during infection against the successive waves of occurring VATs. In addition, active destruction of the host B-cell compartment occurs dur-ing infection, affecting both trypanosome specific and non-specific B-cell memory. These finding will be discussed in the context of the long string of vaccine failure results that have hampered the initiation of an effective vaccine program for trypanosomiasis. Finally, this chapter will also provide new insights into antibody engineering that allow interfering with trypanosome biology in ways that are not part of the natural evolutionary pressure. Hence, possible new tools can be developed that can help in a sustainable long term battle against both human and animal trypanosomiasis.
|Title of host publication||Trypanosomes and trypanosomiasis|
|Editors||Stefan Magez, Magdalena Radwanska|
|Place of Publication||Vienna|
|Publication status||Published - 2014|
- African Trypanosomiasis
- Immune escape