title: Redirection of the immune response to the functional catalytic domain of the cystein proteinase cruzipain improves protective immunity against Trypanosoma cruzi infection.
abstract: 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.
authors.affiliation: Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral (IDEHU), Universidad de BuenosAires, 1113 Buenos Aires, Argentina.
authors.forename: Silvia I
authors.initials: SI
authors.lastname: Cazorla
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Frank
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Becker
authors.forename: María
authors.initials: M
authors.lastname: Arnaiz
authors.forename: Gerardo A
authors.initials: GA
authors.lastname: Mirkin
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Corral
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzmán
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Malchiodi
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D014355:Chagas Disease / Q000517:prevention & control*; D003546:Cysteine Endopeptidases / Q000276:immunology*; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D018482:Muscle, Skeletal / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D015800:Protozoan Proteins / Q000276:immunology; D016052:Protozoan Vaccines / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D014349:Trypanosoma cruzi / Q000201:enzymology / Q000235:genetics* / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D003546:Cysteine Endopeptidases; C063214:cruzipain