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.
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.
Cazorla
Silvia I
SI
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.
Frank
Fernanda M
FM
Becker
Pablo D
PD
Corral
Ricardo S
RS
Guzmán
Carlos A
CA
Malchiodi
Emilio L
EL
D000281:Administration, Intranasal; D000818:Animals; D000913:Antibodies, Protozoan / Q000032:analysis; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D014355:Chagas Disease / Q000276:immunology / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control*; D003546:Cysteine Endopeptidases / Q000008:administration & dosage* / Q000276:immunology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000473:pathology; D018928:Immunity, Mucosal / Q000276:immunology; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007271:Injections, Intradermal; D007371:Interferon-gamma; D055666:Lipopeptides; D051379:Mice; D008809:Mice, Inbred C3H; D018482:Muscle, Skeletal / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000302:isolation & purification; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D055666:Lipopeptides; D009842:Oligopeptides; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; C106335:macrophage stimulatory lipopeptide 2; D003546:Cysteine Endopeptidases; C063214:cruzipain