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
来源：
VACCINE | 2008年 / 26卷 / 16期
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
相关论文
共 42 条
  • [1] PATHOGENESIS OF CHAGAS-DISEASE
    ANDRADE, ZA
    [J]. RESEARCH IN IMMUNOLOGY, 1991, 142 (02): : 126 - 129
  • [2] DEVELOPMENT OF RESISTANCE TO TRYPANOSOMA-CRUZI IN MICE DEPENDS ON A VIABLE POPULATION OF L3T4+ (CD4+) LYMPHOCYTES-T
    ARAUJO, FG
    [J]. INFECTION AND IMMUNITY, 1989, 57 (07) : 2246 - 2248
  • [3] Specific cleavage sites on human IgG subclasses by cruzipain, the major cysteine proteinase from Trypanosoma cruzi
    Berasain, P
    Carmona, C
    Frangione, B
    Cazzulo, JJ
    Goñi, F
    [J]. MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2003, 130 (01) : 23 - 29
  • [4] Clinical course of Chagas' heart disease: A comparison with dilated cardiomyopathy
    Bestetti, RB
    Muccillo, G
    [J]. INTERNATIONAL JOURNAL OF CARDIOLOGY, 1997, 60 (02) : 187 - 193
  • [5] Efficient systemic and mucosal responses against the HIV-1 Tat protein by prime/boost vaccination using the lipopeptide MALP-2 as adjuvant
    Borsutzky, S
    Ebensen, T
    Link, C
    Becker, PD
    Fiorelli, V
    Cafaro, A
    Ensoli, B
    Guzmán, CA
    [J]. VACCINE, 2006, 24 (12) : 2049 - 2056
  • [6] The mucosal adjuvant macrophage-activating lipopeptide-2 directly stimulates B lymphocytes via the TLR2 without the need of accessory cells
    Borsutzky, S
    Kretschmer, K
    Becker, PD
    Mühlradt, PF
    Kirschning, CJ
    Weiss, S
    Guzmán, CA
    [J]. JOURNAL OF IMMUNOLOGY, 2005, 174 (10) : 6308 - 6313
  • [7] DETECTION OF PARASITE DNA IN CHAGAS HEART-DISEASE
    BRANDARIZ, S
    SCHIJMAN, A
    VIGLIANO, C
    ARTEMAN, P
    VIOTTI, R
    BELDJORD, C
    LEVIN, MJ
    [J]. LANCET, 1995, 346 (8986): : 1370 - 1371
  • [8] THE MAJOR CYSTEINE PROTEINASE (CRUZIPAIN) FROM TRYPANOSOMA-CRUZI IS ENCODED BY MULTIPLE POLYMORPHIC TANDEMLY ORGANIZED GENES LOCATED ON DIFFERENT CHROMOSOMES
    CAMPETELLA, O
    HENRIKSSON, J
    ASLUND, L
    FRASCH, ACC
    PETTERSSON, U
    CAZZULO, JJ
    [J]. MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1992, 50 (02) : 225 - 234
  • [9] Oral vaccination with Salmonella enterica as a cruzipain-DNA delivery system confers protective immunity against trypanosoma cruzi
    Cazorla, Silvia I.
    Becker, Pablo D.
    Frank, Fernanda M.
    Ebensen, Thomas
    Sartori, Maria J.
    Corral, Ricardo S.
    Malchiodi, Emilio L.
    Guzman, Carlos A.
    [J]. INFECTION AND IMMUNITY, 2008, 76 (01) : 324 - 333
  • [10] The major cysteine proteinase of Trypanosoma cruzi:: A valid target for chemotherapy of Chagas disease
    Cazzulo, JJ
    Stoka, V
    Turk, V
    [J]. CURRENT PHARMACEUTICAL DESIGN, 2001, 7 (12) : 1143 - 1156
12345