Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Intranasal
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Animals
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Antibodies, Protozoan / analysis
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Antigens, Protozoan / administration & dosage
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Antigens, Protozoan / immunology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Proliferation
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Chagas Disease / immunology
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Chagas Disease / parasitology
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Chagas Disease / pathology
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Chagas Disease / prevention & control*
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Cysteine Endopeptidases / administration & dosage*
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Cysteine Endopeptidases / immunology*
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Female
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Hypersensitivity, Delayed / pathology
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Immunity, Mucosal / immunology
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Immunization Schedule
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Immunization, Secondary
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Injections, Intradermal
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Interferon-gamma
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Lipopeptides
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Mice
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Mice, Inbred C3H
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Muscle, Skeletal / pathology
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Myocardium / pathology
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Oligopeptides / administration & dosage
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Oligopeptides / immunology
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Oligopeptides / pharmacology
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Protozoan Proteins / administration & dosage
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Protozoan Proteins / immunology
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Protozoan Vaccines / administration & dosage
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Protozoan Vaccines / immunology
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / immunology
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Spleen / immunology
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Toll-Like Receptor 2 / agonists
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Trypanosoma cruzi / immunology*
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Trypanosoma cruzi / isolation & purification
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Vaccination*
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / immunology
Substances
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Antibodies, Protozoan
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Antigens, Protozoan
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Lipopeptides
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Oligopeptides
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Protozoan Proteins
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Protozoan Vaccines
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Recombinant Proteins
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Tlr2 protein, mouse
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Toll-Like Receptor 2
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Vaccines, Synthetic
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Interferon-gamma
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macrophage stimulatory lipopeptide 2
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Cysteine Endopeptidases
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cruzipain