CONICET | Buscador de Institutos y Recursos Humanos

Several vaccines against Chagas disease have been studied; however, all vaccination regimens tested so far conferred partial immunity. Despite the strong immune response elicited by vaccination, the parasite survival suggests that, similarly to what happens in natural infection, the immune response is either insufficient or inherently inadequate. The major cystein proteinase, cruzipain (Cz), has a catalytic domain and a C-terminal extension. Although the role of the later domain is unknown, is the major immunogenic part in infected humans. Immunization employing full-length rCz or its N- and C-terminal domains demonstrated that the C-terminal domain allows Cz to circumvent the immune response to the catalytic N-terminal. This is a property of the molecule itself, since inoculation of rCz produces a similar effect than Cz in natural or experimental infection. Cz is not the only T. cruzi antigen having a highly immunogenic region of unknown function, which suggest an overall immune escape strategy developed during evolution. In addition, we demonstrated that by immunizing with the N-terminal domain alone, it is possible to differentially orient the host immune response providing a better protection than that elicited by full-length Cz. This observation has an important implication in terms of optimizing a rational vaccine design.