• Prime-boost immunization with cruzipain co-administered with MALP-2 triggers a protective immune response able to decrease parasite burden and tissue injury in an experimental Trypanosoma cruzi infection model.

      Cazorla, SI; Frank, FM; Becker, PD; Corral, RS; Guzmán, CA; Malchiodi, EL; Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956 4to P, 1113 Buenos Aires, Argentina; Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Argentina; Department of Vaccinology, Helmholtz Centre for Infection Research, Inhoffenstraße 7, D-38124 Braunschweig, Germany. (2008-04-07)
      Cruzipain (Cz), a key Trypanosoma cruzi enzyme, is a main candidate antigen for vaccines against Chagas' disease. We evaluated a vaccination protocol based on intradermal priming with recombinant Cz and intranasal boosting with rCz co-administered with a derivative of the TLR2/6 agonist MALP-2. Vaccination triggered strong systemic and mucosal antibody responses, and a vigorous cell-mediated immunity characterized by lymphoproliferation, DTH reactivity and IFN-gamma production. The immune responses protected against a lethal trypomastigote challenge and, upon sub-lethal infection, immunized mice showed reduction of tissue damage and normal enzymatic markers of muscle injury. This prime-boost regimen appears promising for further development, since warranted survival, provided efficient control of parasite load and restricted inflammatory myopathy.