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 Tryponosoma cruzi infection model

被引:41
作者
Cazorla, Silvia I. [1 ,2 ,3 ]
Frank, Fernanda M. [1 ,2 ]
Becker, Pablo D. [3 ]
Corral, Ricardo S. [4 ]
Guzman, Carlos A. [3 ]
Malchiodi, Emilio L. [1 ,2 ]
机构
[1] Univ Buenos Aires, Catedra Immunol & Inst Estudios Inmunidad Humoral, IDEHU, CONICET,Fac Farm & Bioquim, RA-1113 Buenos Aires, DF, Argentina
[2] Univ Buenos Aires, Dept Microbiol Parasitol & Immunol, Fac Med, RA-1113 Buenos Aires, DF, Argentina
[3] Helmholtz Ctr Infect Res, Dept Vaccinol, D-38124 Braunschweig, Germany
[4] Hosp Ninos Dr Ricardo Gutierrez, Serv Parasitol Chagas, Buenos Aires, DF, Argentina
关键词
Chagas disease; Trypanosoma cruzi; MALP-2;
D O I
10.1016/j.vaccine.2008.02.011
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cruzipain (Cz), a key Tryponosoma 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 mucosat 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. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1999 / 2009
页数:11
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