Redirection of the Immune Response to the Functional Catalytic Domain of the Cystein Proteinase Cruzipain Improves Protective Immunity against Trypanosoma cruzi Infection

• Autores: Cazorla, Silvia I.; Frank, Fernanda M.; Becker, Pablo D.; Arnaiz, María Rosa; Mirkin, Gerardo A.; Corral, Ricardo S.; Guzman, Carlos A.; Malchiodi, Emilio L.
• Año de publicación: 2010
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Journal of Infectious Diseases 2010; 202(1): 136-144.
• Materia: Trypanosoma cruzi; Enfermedad de Chagas; Endopeptidasas; Péptido Hidrolasas
• Institución: Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"

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.