Artículo
Redirection of the Immune Response to the Functional Catalytic Domain of the Cystein Proteinase Cruzipain Improves Protective Immunity against Trypanosoma cruzi Infection
Registro en:
1537-6613
10.1086/652872.
Autor
Cazorla, Silvia I.
Frank, Fernanda M.
Becker, Pablo D.
Arnaiz, María Rosa
Mirkin, Gerardo A.
Corral, Ricardo S.
Guzman, Carlos A.
Malchiodi, Emilio L.
Resumen
Fil: Cazorla, Silvia I. Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, Buenos Aires; Argentina. Fil: Frank, Fernanda M. Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, Buenos Aires; Argentina. Fil: Becker, Pablo D. Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, InhoffenstraΒe 7, D-38124 Braunschweig; Alemania. Fil: Arnaiz, María Rosa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina. Fil: Mirkin, Gerardo A. Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires; Argentina. Fil: Corral, Ricardo S. Servicio de Parasitología-Chagas, Hospital de Niños Ricardo Gutiérrez, Buenos Aires; Argentina. Fil: Guzman, Carlos A. Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, InhoffenstraΒe 7, D-38124 Braunschweig; Alemania. Fil: Malchiodi, Emilio L. Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, Buenos Aires; Argentina. Despite the strong immune responses elicited after natural infection with Trypanosoma cruzi or vaccination against it, parasite survival suggests that these responses are insufficient or inherently inadequate. T. cruzi contains a major cystein proteinase, cruzipain, which has a catalytic N-terminal domain and a C-terminal extension. Immunizations that employed recombinant cruzipain or its N- and C-terminal domains allowed evaluation of the ability of cruzipain to circumvent responses against the catalytic domain. This phenomenon is not a property of the parasite but of cruzipain itself, because recombinant cruzipain triggers a response similar to that of cruzipain during natural or experimental infection. Cruzipain is not the only antigen with a highly immunogenic region of unknown function that somehow protects an essential domain for parasite survival. However, our studies show that this can be reverted by using the N- terminal domain as a tailored immunogen able to redirect host responses to provide enhanced protection.