CONICET | Buscador de Institutos y Recursos Humanos

The increase of human babesiosis is of major concern to health authorities. In the USA, most of these cases are due to infections with Babesia microti, whereas in Europe B. divergens is the major cause of clinical disease in humans. Cattle can be vaccinated with soluble parasite antigens (SPA) of B. divergens that are released by the parasite during proliferation. The major component in SPA preparations appeared to be a 37kDa merozoite surface protein that is anchored in the merozoite membrane by a glycosylphosphatidylinositol (GPI) anchor. Animals could be protected by vaccination with the recombinant 37kDa protein expressed in E. coli, provided the protein had a hydrophobic terminal sequence. Based on this knowledge, a recombinant vaccine was developed against B. canis infection in dogs. A 40kDa merozoite surface protein with a putatively GPI-anchoring site was discovered in SPA preparations of B. canis. The entire 40kDa protein (including the terminal hydrophobic sequences) was expressed in E. coli and shown to successfully immunize dogs. In order to identify similar GPI-anchored proteins of B. microti, the genome was analysed. Here it is shown that B. microti encodes all proteins necessary for GPI assembly and its subsequent protein transfer. In addition, in total 21 genes encoding for GPI-anchored proteins were detected, some of which reacted particularly strong with sera from B. microti-infected human patients. Reactivity of antibodies with GPI-anchored merozoite proteins appears to be dependent on the structural conformation of themolecule. It is suggested that the 3D structure of the protein that is anchored in the membrane is different from that of the protein that has been cut by specific phospholipases that target the GPI anchor. The clarification of the specific conformation that is able to induce a protective immune response will open the way to rational design ofrecombinant vaccines.

enviar mensaje